287 results on '"Jinyu An"'
Search Results
2. Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy.
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Tang, Bufu, Zhu, Jinyu, Shi, Yueli, Wang, Yajie, Zhang, Xiaojie, Chen, Biao, Fang, Shiji, Yang, Yang, Zheng, Liyun, Qiu, Rongfang, Weng, Qiaoyou, Xu, Min, Zhao, Zhongwei, Tu, Jianfei, Chen, Minjiang, and Ji, Jiansong
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LEUCINE zippers , *PROGNOSIS , *GENE expression , *CELLULAR control mechanisms , *HEPATOCELLULAR carcinoma , *LEUCINE , *LUCIFERASES , *HUMAN carcinogenesis - Abstract
Background: The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks. Methods: Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification–mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC. Results: We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT). Conclusions: Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC. [ABSTRACT FROM AUTHOR]
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- 2024
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3. PKIB, a Novel Target for Cancer Therapy.
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Musket, Anna, Moorman, Jonathan P., Zhang, Jinyu, and Jiang, Yong
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PROTEIN kinase inhibitors ,CYTOLOGY ,CYCLIC adenylic acid ,GENETIC regulation ,GENE expression ,CYCLIC-AMP-dependent protein kinase ,SERINE/THREONINE kinases - Abstract
The serine-threonine kinase protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent intracellular protein with multiple roles in cellular biology including metabolic and transcription regulation functions. The cAMP-dependent protein kinase inhibitor β (PKIB) is one of three known endogenous protein kinase inhibitors of PKA. The role of PKIB is not yet fully understood. Hormonal signaling is correlated with increased PKIB expression through genetic regulation, and increasing PKIB expression is associated with decreased cancer patient prognosis. Additionally, PKIB impacts cancer cell behavior through two mechanisms; the first is the nuclear modulation of transcriptional activation and the second is the regulation of oncogenic AKT signaling. The limited research into PKIB indicates the oncogenic potential of PKIB in various cancers. However, some studies suggest a role of PKIB in non-cancerous disease states. This review aims to summarize the current literature and background of PKIB regarding cancer and related issues. In particular, we will focus on cancer development and therapeutic possibilities, which are of paramount interest in PKIB oncology research. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder.
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Zou, Zhili, Huang, Yulan, Maes, Michael, Wang, Jinyu, He, Ying, Min, Wenjiao, and Zhou, Bo
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PANIC disorders ,GENE expression ,HORMONES ,HYDROCORTISONE ,ADRENOCORTICOTROPIC hormone - Abstract
Objective: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). Methods: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. Results: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). Conclusions: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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5. The Glycine soja cytochrome P450 gene GsCYP82C4 confers alkaline tolerance by promoting reactive oxygen species scavenging.
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Jinyu Wu, Yangyang Fang, Liankun Xu, Xiaoxia Jin, Iqbal, Anam, Nisa, Zaib_un, Ali, Naila, Chao Chen, Shah, Anis Ali, and Gatasheh, Mansour K.
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CYTOCHROME P-450 , *REACTIVE oxygen species , *GENE expression , *GLYCINE , *METABOLITES , *SOYBEAN - Abstract
Recent studies have demonstrated the crucial role of Cytochrome P450 enzymes (CYPs) in the production of secondary metabolites, phytohormones and antioxidants in plants. However, their functional characterization specifically under alkaline stress remains elusive. CYP82C4 was the key gene screened from a family of wild soybean CYPs in our previous studies. The aim of this present study was to clone the Glycine soja GsCYP82C4 gene and characterize its functions in Arabidopsis and Glycine max. The results showed that the GsCYP82C4 gene displayed a high expression in different plant tissues at mature stages compared to young stages. Further, higher temporal expression of the GsCYP82C4 gene was noted at 6, 12 and 24 h time points after alkali treatment in leaves compared to roots. In addition, overexpression of GsCYP82C4 improved alkaline stress tolerance in Arabidopsis via increased root lengths and fresh biomass and strengthened the antioxidant defense system via a reduction in superoxide radicals in transgenic lines compared to wild type (WT) and atcyp82c4 mutants. Further, the expression levels of stress-related marker genes were up-regulated in GsCYP82C4 OX lines under alkali stress. The functional analysis of GsCYP82C4 overexpression in soybean displayed better hairy root growth, increased fresh weight, higher antioxidant enzyme activities and reduced lipid peroxidation rates in OX lines compared to the soybean WT (K599) line. In total, our study displayed positive roles of GsCYP82C4 overexpression in both Arabidopsis and Glycine max to alleviate alkaline stress via altering expression abundance of stress responsive genes, stronger roots, higher antioxidant enzyme activities as well as reduced rates of lipid peroxidation and superoxide radicals. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Profiles of Immune Cell Infiltration in Carotid Artery Atherosclerosis Based on Gene Expression Data
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Long Wang, Beibei Gao, Mingyue Wu, Wei Yuan, Ping Liang, and Jinyu Huang
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immune infiltration ,immune cells ,atherosclerosis ,gene expression ,T cells ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Since immune infiltration is closely associated with the progression and prognosis of atherosclerosis, we aimed to describe the abundance of 24 immune cell types within atherosclerotic tissues. In the current study, we used the Immune Cell Abundance Identifier (ImmuCellAI), a web-based tool, to estimate the abundance of 24 immune cells based on the microarray profiles of atherosclerotic carotid artery samples to analyze the proportions and the dysregulation of immune cell types within carotid atherosclerosis. We found that atherosclerotic immune cells had a diverse landscape dominated by T cells and myeloid cells and that macrophages and dendritic cells (DCs) showed different abundance in normal and atherosclerotic tissues. Moreover, the expression of macrophages was closely related to the level of the expression of DCs and of exhausted T cells, while the expression of T-helper type 1 (Th1) cells was strongly correlated with the expression of T-helper type 2 (Th2) cells and effector memory cells. Our data confirm a distinct profile of atherosclerosis-infiltrating immune cell subpopulations, which may inspire an immunological direction for research on atherosclerosis.
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- 2021
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7. Effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks.
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Hongzhi Wu, Jiajun Xie, Weiqi Peng, Fengjie Ji, Jinyu Qian, Qian Shen, and Guanyu Hou
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FATTY acid-binding proteins ,GENE expression ,LIPOPROTEIN lipase ,HIGH density lipoproteins ,LIPIDS ,CHYLOMICRONS ,PECTORALIS muscle - Abstract
Exogenous supplementation of guanidinoacetic acid can mechanistically regulate the energy distribution in muscle cells. This study aimed to investigate the effects of guanidinoacetic acid supplementation on liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks. We randomly divided 480 42 days-old female Jiaji ducks into four groups with six replicates and 20 ducks for each replicate. The control group was fed the basal diet, and the experimental groups were fed the basal diet with 400, 600, and 800 mg/kg (GA400, GA600, and GA800) guanidinoacetic acid, respectively. Compared with the control group, (1) the total cholesterol (p = 0.0262), triglycerides (p = 0.0357), malondialdehyde (p = 0.0452) contents were lower in GA400, GA600 and GA800 in the liver; (2) the total cholesterol (p = 0.0365), triglycerides (p = 0.0459), and malondialdehyde (p = 0.0326) contents in breast muscle were decreased in GA400, GA600 and GA800; (3) the high density lipoprotein (p = 0.0356) and apolipoprotein-A1 (p = 0.0125) contents were increased in GA600 in the liver; (4) the apolipoprotein-A1 contents (p = 0.0489) in breast muscle were higher in GA600 and GA800; (5) the lipoprotein lipase contents (p = 0.0325) in the liver were higher in GA600 and GA800; (6) the malate dehydrogenase contents (p = 0.0269) in breast muscle were lower in GA400, GA600, and GA800; (7) the insulin induced gene 1 (p = 0.0326), fatty acid transport protein 1 (p = 0.0412), and lipoprotein lipase (p = 0.0235) relative expression were higher in GA400, GA600, and GA800 in the liver; (8) the insulin induced gene 1 (p = 0.0269), fatty acid transport protein 1 (p = 0.0234), and lipoprotein lipase (p = 0.0425) relative expression were increased in GA400, GA600, and GA800 in breast muscle. In this study, the optimum dosage of 600 mg/kg guanidinoacetic acid improved the liver and breast muscle fat deposition, lipid levels, and lipid metabolism-related gene expression in ducks. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Chicken Interferon-Alpha and -Lambda Exhibit Antiviral Effects against Fowl Adenovirus Serotype 4 in Leghorn Male Hepatocellular Cells.
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Lai, Jinyu, He, Xingchen, Zhang, Rongjie, Zhang, Limei, Chen, Libin, He, Fengping, Li, Lei, Yang, Liangyu, Ren, Tao, and Xiang, Bin
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TYPE I interferons , *CHICKENS , *ADENOVIRUSES , *POULTRY , *GENE expression , *INTERFERON alpha , *VIRAL genomes - Abstract
Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens. [ABSTRACT FROM AUTHOR]
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- 2024
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9. AcMYB10 Involved in Anthocyanin Regulation of 'Hongyang' Kiwifruit Induced via Fruit Bagging and High-Postharvest-Temperature Treatments.
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Yu, Min, Xiong, Jinyu, Dong, Kun, Quan, Xin, Guo, Hao, Huo, Junwei, Qin, Dong, Wang, Yanchang, Lu, Xuemei, and Zhu, Chenqiao
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KIWIFRUIT , *ANTHOCYANINS , *FRUIT , *GENE expression , *HIGH temperatures - Abstract
Light and temperature are key factors influencing the accumulation of anthocyanin in fruit crops. To assess the effects of fruit bagging during development and high post-ripening temperature on 'Hongyang' kiwifruit, we compared the pigmentation phenotypes and expression levels of anthocyanin-related genes between bagged and unbagged treatments, and between 25 °C and 37 °C postharvest storage temperatures. Both the bagging and 25 °C treatments showed better pigmentation phenotypes with higher anthocyanin concentrations. The results of the qRT-PCR analysis revealed that the gene expression levels of LDOX (leucoanthocyanidin dioxygenase), F3GT (UDP-flavonoid 3-O-glycosyltransferase), AcMYB10, and AcbHLH42 were strongly correlated and upregulated by both the bagging treatment and 25 °C storage. The results of bimolecular fluorescence complementation and luciferase complementation imaging assays indicated an interaction between AcMYB10 and AcbHLH42 in plant cells, whereas the results of a yeast one-hybrid assay further demonstrated that AcMYB10 activated the promoters of AcLODX and AcF3GT. These results strongly suggest that enhanced anthocyanin synthesis is caused by the promoted expression of AcLODX and AcF3GT, regulated by the complex formed by AcMYB10–AcbHLH42. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Exogenous Melatonin Promotes Glucoraphanin Biosynthesis by Mediating Glutathione in Hairy Roots of Broccoli (Brassica oleracea L. var. italica Planch).
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Bao, Jinyu, Yang, Jie, Lu, Xu, Ma, Lei, Shi, Xiaotong, Lan, Shimin, Zhao, Yi, Cao, Jie, Ma, Shaoying, and Li, Sheng
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BROCCOLI ,COLE crops ,BIOSYNTHESIS ,GLUTATHIONE ,GENE expression ,TANDEM mass spectrometry - Abstract
To investigate the mechanism of melatonin (MT)-mediated glutathione (GSH) in promoting glucoraphanin (GRA) and sulforaphane (SF) synthesis, the gene expression pattern and protein content of hairy broccoli roots under MT treatment were analyzed by a combination of RNA-seq and tandem mass spectrometry tagging (TMT) techniques in this study. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that both proteins and mRNAs with the same expression trend were enriched in the "Glutathione metabolism (ko00480)" and "Proteasome (ko03050)" pathways, and most of the differentially expressed genes (DEGs) and differentially abundant proteins (DAPs) regulating the two pathways were downregulated. The results showed that endogenous GSH concentration and GR activity were increased in hairy roots after MT treatment. Exogenous GSH could promote the biosynthesis of GRA and SF, and both exogenous MT and GSH could upregulate the expression of the GSTF11 gene related to the sulfur transport gene, thus promoting the biosynthesis of GRA. Taken together, this study provides a new perspective to explore the complex molecular mechanisms of improving GRA and SF synthesis levels by MT and GSH regulation. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Infection‐specific transcriptional patterns of the maize pathogen Cochliobolus heterostrophus unravel genes involved in asexual development and virulence.
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Yu, Huilin, Zhang, Jiyue, Fan, Jinyu, Jia, Wantong, Lv, Yanan, Pan, Hongyu, and Zhang, Xianghui
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METABOLITES ,HISTONE acetyltransferase ,GENE expression ,NADPH oxidase ,TRANSCRIPTION factors ,CORN diseases ,CORN - Abstract
Southern corn leaf blight (SCLB) caused by Cochliobolus heterostrophus is a destructive disease that threatens global maize (Zea mays) production. Despite many studies being conducted, very little is known about molecular processes employed by the pathogen during infection. There is a need to understand the fungal arms strategy and identify novel functional genes as targets for fungicide development. Transcriptome analysis based on RNA sequencing was carried out across conidia germination and host infection by C. heterostrophus. The present study revealed major changes in C. heterostrophus gene expression during host infection. Several differentially expressed genes (DEGs) induced during C. heterostrophus infection could be involved in the biosynthesis of secondary metabolites, peroxisome, energy metabolism, amino acid degradation and oxidative phosphorylation. In addition, histone acetyltransferase, secreted proteins, peroxisomal proteins, NADPH oxidase and transcription factors were selected for further functional validation. Here, we demonstrated that histone acetyltransferases (Hat2 and Rtt109), secreted proteins (Cel61A and Mep1), peroxisomal proteins (Pex11A and Pex14), NADPH oxidases (NoxA, NoxD and NoxR) and transcription factors (Crz1 and MtfA) play essential roles in C. heterostrophus conidiation, stress adaption and virulence. Taken together, our study revealed major changes in gene expression associated with C. heterostrophus infection and identified a diverse repertoire of genes critical for successful infection. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Immunopromoter improves liver apoptosis and immune response in Shaoxing ducklings.
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Liu, Jinyu, Chen, Li, Li, Guoqin, Tian, Yong, Zeng, Tao, Xu, Wenwu, Xu, Qi, Lu, Lizhi, and Gu, Tiantian
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DUCKLINGS , *IMMUNE response , *GENE expression , *MALLARD , *CHLOROGENIC acid , *LIVER , *POULTRY growth , *ANIMAL culture - Abstract
Antibiotics as feed additives, play a vital role in animal husbandry. However, overused antibiotics could cause endogenous infections in animals, and even endanger human health through the food chain. And immunopotentiators can make the low immune function improve and accelerate the induction of immune response. The aim of this study was to investigate the effects of five different immunopotentiators on the expression of liver apoptosis and immune factor related genes in Shaoxing ducklings (Anas Platyrhynchos). A total of 150 one-day-old Shaoxing ducklings were randomly divided into six groups including saline, chlorogenic acid, β-D-glucan, astragalus flavone, CpG DNA and chicken IgG, which were injected subcutaneously into the neck, respectively. At 18 days old, the liver tissues were collected to detecte the mRNA and protein expression levels of inflammatory and apoptosis-related genes. The results showed that compared with the control group, the mRNA and protein levels of liver Bcl2 with chlorogenic acid, β-D-glucan, astragalus flavone, CpG-DNA and chicken IgG were significantly decreased (p < 0.05), while the expression level of Caspase3 was up-regulated in some different degrees. In addition,The expression levels of liver iNOS and COX2 were significantly increased after the injection of five immunopotentiators (p < 0.05), and the mRNA levels of IFN-α, IFN-β, IL-1β, RIG-I, TLR3 and TLR7 genes were also significantly up-regulated compared with the control group (p < 0.05). In conclusion, chlorogenic acid, β-D-glucan, astragalus flavone, CpG-DNA and chicken IgG can be used as immunopotentiators to regulate duck innate immunity. This study provides a new way to prevent important infectious diseases of ducks, and also provides a certain reference for the application of antibiotic substitutes in animal production. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Overexpression of an ART1-Interacting Gene OsNAC016 Improves Al Tolerance in Rice.
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Liu, Fuhang, Ma, Dan, Yu, Jinyu, Meng, Ran, Wang, Zhigang, Zhang, Baolei, Chen, Xingxiang, Zhang, Lin, Peng, Liyun, and Xia, Jixing
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GENETIC overexpression ,IMMOBILIZED proteins ,NUCLEAR proteins ,GENE expression ,IMMUNOSTAINING - Abstract
Rice (Oryza sativa) exhibits tremendous aluminum (Al)-tolerance. The C2H2-transcription factor (TF) ART1 critically regulates rice Al tolerance via modulation of specific gene expression. However, little is known about the posttranscriptional ART1 regulation. Here, we identified an ART1-interacted gene OsNAC016 via a yeast two-hybrid (Y2H) assay. OsNAC016 was primarily expressed in roots and weakly induced by Al. Immunostaining showed that OsNAC016 was a nuclear protein and localized in all root cells. Knockout of OsNAC016 did not alter Al sensitivity. Overexpression of OsNAC016 resulted in less Al aggregation within roots and enhanced Al tolerance in rice. Based on transcriptomic and qRT-PCR evaluations, certain cell-wall-related or ART-regulated gene expressions such as OsMYB30 and OsFRDL4 were altered in OsNAC016-overexpressing plants. These results indicated that OsNAC016 interacts with ART1 to cooperatively regulate some Al-tolerance genes and is a critical regulatory factor in rice Al tolerance. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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14. Selective RNA Processing and Stabilization are Multi‐Layer and Stoichiometric Regulators of Gene Expression in Escherichia coli.
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Liu, Daixi, Lv, Haibo, Wang, Yafei, Chen, Jinyu, Li, Dexin, and Huang, Ranran
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GENE expression ,REGULATOR genes ,ESCHERICHIA coli ,HAIRPIN (Genetics) ,RNA ,SYNTHETIC biology - Abstract
Selective RNA processing and stabilization (SRPS) facilitates the differential expression of multiple genes in polycistronic operons. However, how the coordinated actions of SRPS‐related enzymes affect stoichiometric regulation remains unclear. In the present study, the first genome‐wide targetome analysis is reported of these enzymes in Escherichia coli, at a single‐nucleotide resolution. A strictly linear relationship is observed between the RNA pyrophosphohydrolase processing ratio and scores assigned to the first three nucleotides of the primary transcript. Stem‐loops associated with PNPase targetomes exhibit a folding free energy that is negatively correlated with the termination ratio of PNPase at the 3′ end. More than one‐tenth of the RNase E processing sites in the 5′‐untranslated regions(UTR) form different stem‐loops that affect ribosome‐binding and translation efficiency. The effectiveness of the SRPS elements is validated using a dual‐fluorescence reporter system. The findings highlight a multi‐layer and quantitative regulatory method for optimizing the stoichiometric expression of genes in bacteria and promoting the application of SRPS in synthetic biology. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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15. The effect and mechanism of iodophors on the adhesion and virulence of Staphylococcus aureus biofilms attached to artificial joint materials.
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Chen, Sihui, Jiang, Yi, Wang, Wei, Chen, Junjie, and Zhu, Jinyu
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ARTIFICIAL limbs ,ALLOYS ,MOLYBDENUM ,CLINICAL trials ,MICROSCOPY ,CHROMIUM ,BIOFILMS ,POLYETHYLENE ,INFECTION ,IODOPHORS ,GENE expression ,STAPHYLOCOCCUS aureus ,RESEARCH funding ,MICROBIAL virulence ,TITANIUM ,COMPLICATIONS of prosthesis - Abstract
Background: Iodophors are known to be a treatment for biofilm-related periprosthetic joint infection. However, the efficacy and mechanism of eradicating biofilms from different artificial joint materials after iodophor treatment are unknown. This study was conducted to understand the effect and mechanism of iodophors with respect to the adhesion and virulence of Staphylococcus aureus biofilms attached to artificial joint materials. Methods: Biofilms of Staphylococcus aureus strains were grown on titanium alloy, cobalt chromium molybdenum and polyethylene coupons, which are commonly used materials for artificial joints, for 24 h. Afterward, all coupons were divided into experimental and control groups: (1) exposed to a 0.5 ± 0.05% iodophor for 5 min and (2) exposed to phosphate-buffered saline for 5 min. To gauge the level of biofilm, colony forming units (CFU), live/dead staining confocal microscopy and crystal violet staining were used. Meanwhile, the expression of icaACDR and clfA, which are related to virulence and adhesion, was examined in both the experimental and control groups. Results: A roughly three-log decrease in CFU/cm
2 was seen in the viable plate count compared to the control group. Confocal imaging and crystal violet staining verified the CFU data. Moreover, the expression of icaACDR was reduced on three different orthopaedic implant materials, and the expression of clfA was also inhibited on titanium alloy coupons exposed to the iodophor. Conclusions: Our results indicated that exposure to an iodophor for 5 min could significantly eliminate biofilms. When Staphylococcus aureus that had adhered to these three materials, which were used for artificial joints, was treated with an iodophor for 5 min, the expression of icaACDR was significantly reduced. This provides strong evidence for clinically clearing periprosthetic joint infections without removing the artificial joints. [ABSTRACT FROM AUTHOR]- Published
- 2023
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16. Actin-Related Protein 4 Interacts with PIE1 and Regulates Gene Expression in Arabidopsis
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Wen-Feng Nie and Jinyu Wang
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AtARP4 ,epigenetic ,gene expression ,chromatin remodeling ,Genetics ,QH426-470 - Abstract
As essential structural components of ATP-dependent chromatin-remodeling complex, the nucleolus-localized actin-related proteins (ARPs) play critical roles in many biological processes. Among them, ARP4 is identified as an integral subunit of chromatin remodeling complex SWR1, which is conserved in yeast, humans and plants. It was shown that RNAi mediated knock-down of Arabidopsisthaliana ARP4 (AtARP4) could affect plant development, specifically, leading to early flowering. However, so far, little is known about how ARP4 functions in the SWR1 complex in plant. Here, we identified a loss-of-function mutant of AtARP4 with a single nucleotide change from glycine to arginine, which had significantly smaller leaf size. The results from the split luciferase complementation imaging (LCI) and yeast two hybrid (Y2H) assays confirmed its physical interaction with the scaffold and catalytic subunit of SWR1 complex, photoperiod-independent early flowering 1 (PIE1). Furthermore, mutation of AtARP4 caused altered transcription response of hundreds of genes, in which the number of up-regulated differentially expressed genes (DEGs) was much larger than those down-regulated. Although most DEGs in atarp4 are related to plant defense and response to hormones such as salicylic acid, overall, it has less overlapping with other swr1 mutants and the hta9 hta11 double-mutant. In conclusion, our results reveal that AtARP4 is important for plant growth and such an effect is likely attributed to its repression on gene expression, typically at defense-related loci, thus providing some evidence for the coordination of plant growth and defense, while the regulatory patterns and mechanisms are distinctive from other SWR1 complex components.
- Published
- 2021
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17. Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.
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Zhang, Jinyu, Zhang, Yi, Khanal, Sushant, Cao, Dechao, Zhao, Juan, Dang, Xindi, Nguyen, Lam Ngoc Thao, Schank, Madison, Wu, Xiao Y., Jiang, Yong, Ning, Shunbin, Wang, Ling, El Gazzar, Mohamed, Moorman, Jonathan P., Guo, Haitao, and Yao, Zhi Q.
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CHRONIC hepatitis B ,VIRAL replication ,HEPATITIS B virus ,VIRAL DNA ,GENETIC vectors ,GENE expression - Abstract
The presence of hepatitis B virus (HBV) covalently closed circular (ccc) DNA (cccDNA), which serves as a template for viral replication and integration of HBV DNA into the host cell genome, sustains liver pathogenesis and constitutes an intractable barrier to the eradication of chronic HBV infection. The current antiviral therapy for HBV infection, using nucleos(t)ide analogues (NAs), can suppress HBV replication but cannot eliminate integrated HBV DNA and episomal cccDNA. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 is a powerful genetic tool that can edit integrated HBV DNA and minichromosomal cccDNA for gene therapy, but its expression and delivery require a viral vector, which poses safety concerns for therapeutic applications in humans. In the present study, we used synthetic guide RNA (gRNA)/Cas9‐ribonucleoprotein (RNP) as a nonviral formulation to develop a novel CRISPR/Cas9‐mediated gene therapy for eradicating HBV infection. We designed a series of gRNAs targeting multiple specific HBV genes and tested their antiviral efficacy and cytotoxicity in different HBV cellular models. Transfection of stably HBV‐infected human hepatoma cell line HepG2.2.15 with HBV‐specific gRNA/Cas9 RNPs resulted in a substantial reduction in HBV transcripts. Specifically, gRNA5 and/or gRNA9 RNPs significantly reduced HBV cccDNA, total HBV DNA, pregenomic RNA, and HBV antigen (HBsAg, HBeAg) levels. T7 endonuclease 1 (T7E1) cleavage assay and DNA sequencing confirmed specific HBV gene cleavage and mutations at or around the gRNA target sites. Notably, this gene‐editing system did not alter cellular viability or proliferation in the treated cells. Because of their rapid DNA cleavage capability, low off‐target effects, low risk of insertional mutagenesis, and readiness for use in clinical application, these results suggest that synthetic gRNA/Cas9 RNP‐based gene‐editing can be utilized as a promising therapeutic drug for eradicating chronic HBV infection. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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18. Transcriptome Analysis of Leg Muscles and the Effects of ALOX5 on Proliferation and Differentiation of Myoblasts in Haiyang Yellow Chickens.
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Yin, Xumei, Fang, Wenna, Yuan, Manman, Sun, Hao, and Wang, Jinyu
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FIBROBLAST growth factors ,FACIOSCAPULOHUMERAL muscular dystrophy ,GENE expression ,MITOGEN-activated protein kinases ,MYOBLASTS ,LEG muscles ,GENETIC overexpression - Abstract
Skeletal muscle growth and development from embryo to adult consists of a series of carefully regulated changes in gene expression. This study aimed to identify candidate genes involved in Haiyang Yellow Chickens' growth and to understand the regulatory role of the key gene ALOX5 (arachidonate 5-lipoxygenase) in myoblast proliferation and differentiation. In order to search the key candidate genes in the process of muscle growth and development, RNA sequencing was used to compare the transcriptomes of chicken muscle tissues at four developmental stages and to analyze the effects of ALOX5 gene interference and overexpression on myoblast proliferation and differentiation at the cellular level. The results showed that 5743 differentially expressed genes (DEGs) (|fold change| ≥ 2; FDR ≤ 0.05) were detected by pairwise comparison in male chickens. Functional analysis showed that the DEGs were mainly involved in the processes of cell proliferation, growth, and developmental process. Many of the DEGs, such as MYOCD (Myocardin), MUSTN1 (Musculoskeletal Embryonic Nuclear Protein 1), MYOG (MYOGenin), MYOD1 (MYOGenic differentiation 1), FGF8 (fibroblast growth factor 8), FGF9 (fibroblast growth factor 9), and IGF-1 (insulin-like growth factor-1), were related to chicken growth and development. KEGG pathway (Kyoto Encyclopedia of Genes and Genomes pathway) analysis showed that the DEGs were significantly enriched in two pathways related to growth and development: ECM-receptor interaction (Extracellular Matrix) and MAPK signaling pathway (Mitogen-Activated Protein Kinase). With the extension of differentiation time, the expression of the ALOX5 gene showed an increasing trend, and it was found that interference with the ALOX5 gene could inhibit the proliferation and differentiation of myoblasts and that overexpression of the ALOX5 gene could promote the proliferation and differentiation of myoblasts. This study identified a range of genes and several pathways that may be involved in regulating early growth, and it can provide theoretical research for understanding the regulation mechanism of muscle growth and development of Haiyang Yellow Chickens. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Effects of Tributyrin Supplementation on Liver Fat Deposition, Lipid Levels and Lipid Metabolism-Related Gene Expression in Broiler Chickens
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Tiantian Gu, Mingcai Duan, Jinyu Liu, Li Chen, Yong Tian, Wenwu Xu, Tao Zeng, and Lizhi Lu
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Genetics ,tributyrin ,fat deposition ,lipid metabolism ,gene expression ,broiler chicken ,Genetics (clinical) - Abstract
The objective of this study was to investigate the effects of tributyrin supplementation on liver fat metabolism in broiler chickens. Two hundred and forty broilers were randomly allocated into two experimental groups (6 replicates per treatment; 20 chickens in each replicate): the control group (CN), which received a basal diet, and the tributyrin group (TB), which received a basal diet supplemented with 1 g/kg of tributyrin. The experimental period lasted 37 days. The results showed that in the liver, broilers supplemented with tributyrin had higher content of high-density lipoprotein cholesterol (HDL-C) (p < 0.05). Liver hepatic lipase (HL), lipoprotein lipase (LPL) and total lipid (TL) activity were significantly lower than in the TB group than that in the NC group. Meanwhile, the diet supplemented with tributyrin had more lipid droplets than the NC group, whereas the TB and NC groups showed no histological abnormalities in the liver. Furthermore, the mRNA expression levels of peroxisome proliferators-activated receptor α (PPARα), proliferators-activated receptor γ (PPARγ), fatty acid synthase (FAS), LPL and adipose triglyceride lipase (ATGL) in the liver were significantly upregulated in the TB group (p < 0.05), while those of the long-chain acyl-CoA-synthetase 1 (ACSL1) mRNA between the TB group and the NC group were not different (p > 0.05). These findings indicated that the diet supplemented with tributyrin could increase fat deposition appropriately by promoting fat synthesis without causing liver tissue damage, which demonstrated that tributyrin can be considered a valid feed additive for broiler chickens.
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- 2022
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20. Identification of differentially expressed genes-related prognostic risk model for survival prediction in breast carcinoma patients
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Jinyu Li, Caixia Ren, Ning Wang, Gena Huang, Man Li, Zuowei Zhao, and Silei Sui
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Oncology ,differentially expressed genes ,Aging ,medicine.medical_specialty ,prognostic risk model ,Breast Neoplasms ,Models, Biological ,breast cancer ,Breast cancer ,Risk Factors ,Internal medicine ,Databases, Genetic ,Gene expression ,medicine ,Humans ,Protein Interaction Maps ,RNA, Messenger ,Stage (cooking) ,prognostic outcome ,Gene ,Proportional Hazards Models ,Framingham Risk Score ,Proportional hazards model ,business.industry ,Gene Expression Profiling ,Cell Biology ,Cell cycle ,Prognosis ,medicine.disease ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,Gene Ontology ,Multivariate Analysis ,Female ,business ,Breast carcinoma ,Research Paper ,Cox regression - Abstract
Since the imbalance of gene expression has been demonstrated to tightly related to breast cancer (BRCA) genesis and growth, common genes expressed of BRCA were screened to explore the essence in-between. In current work, most common differentially expressed genes (DEGs) in various subtypes of BRCA were identified. Functional enrichment analysis illustrated the driving factor of deactivation of the cell cycle and the oocyte meiosis, which critically triggers the development of BRCA. Herein, we constructed a 12-gene prognostic risk model relative to differential gene expression. Subsequently, the K-M curves, analysis on time-ROC curve and Cox regression were performed to assess this risk model by determining the respective prognostic value, and the prediction performance were ascertained for both training and validation cohorts. In addition, multivariate Cox regression was analysed to reveal the independence between risk score and prognostic stage, and the accuracy and sensitivity of prognosis are particularly improved after clinical indicators are included into the analysis. In summary, this study offers novel insights into the imbalance of gene expression within BRCA, and highlights 12 selected genes associated with patient prognosis. The risk model can help individualize treatment for patients at different risks, and propose precise strategies and treatments for BRCA therapy.
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- 2021
21. Mitogen-activated protein kinase 6 regulates NPR1 gene expression and activation during leaf senescence induced by salicylic acid
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Chai, Jinyu, Liu, Jian, Zhou, Jun, and Xing, Da
- Published
- 2014
22. Variation in Rubisco activase (RCAβ) gene promoters and expression in soybean [Glycine max (L.) Merr.]
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Chao, Maoni, Yin, Zhitong, Hao, Derong, Zhang, Jinyu, Song, Haina, Ning, Ailing, Xu, Xiaoming, and Yu, Deyue
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- 2014
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23. Emerging Clues of Regulatory Roles of Circular RNAs through Modulating Oxidative Stress: Focus on Neurological and Vascular Diseases
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Lingfei Li, Lin Jiang, Anwen Shao, Zhenzhen Chen, Hong-Fei Sang, Jingfen Jin, Congguo Yin, Zhumei Ni, Jinyu Huang, Wenqing Xia, and Xiaoli Si
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Nervous system ,Regulation of gene expression ,Aging ,QH573-671 ,RNA ,RNA, Circular ,Review Article ,Cell Biology ,General Medicine ,Biology ,medicine.disease_cause ,Models, Biological ,Biochemistry ,Oxidative Stress ,medicine.anatomical_structure ,Gene Expression Regulation ,Gene expression ,medicine ,Humans ,Vascular Diseases ,Nervous System Diseases ,Cytology ,Neuroscience ,Biogenesis ,Oxidative stress - Abstract
Circular RNAs (circRNAs) are novel noncoding RNAs that play regulatory roles in gene expression. Dysregulation of circRNAs is associated with the development and progression of several diseases, such as diabetes mellitus, nervous system diseases, cardiovascular diseases, and cancer. CircRNAs functionally participate in cell physiological activities through various molecular mechanisms. However, these molecular mechanisms are unclear. Oxidative stress is an essential factor in the pathogenesis of various diseases, including neurological diseases. Emerging roles of circRNAs have been identified in different systems in response to oxidative stress. In this review, we summarize the current understanding of circRNA biogenesis, properties, expression profiles, and the clues indicating the regulatory roles of circRNAs through oxidative stress in various systems, especially the nervous system.
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- 2021
24. TACE responser NDRG1 acts as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC.
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Tang, Bufu, Wang, Yajie, Zhu, Jinyu, Song, Jingjing, Fang, Shiji, Weng, Qiaoyou, Yang, Yang, Tu, Jianfei, Zhao, Zhongwei, Chen, Minjiang, Xu, Min, Chen, Weiqian, and Ji, Jiansong
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RANDOM forest algorithms ,CHEMOEMBOLIZATION ,PRINCIPAL components analysis ,METASTASIS ,BLEPHAROPTOSIS ,GENE expression - Abstract
Background: The treatment efficacy of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) varies widely between individuals. The aim of this study was to identify subtype landscapes and responser related to TACE, and further clarify the regulatory effect and corresponding mechanism of NDRG1 on HCC tumorgenesis and metastasis. Methods: The principal component analysis (PCA) algorithm was used to construct a TACE response scoring (TRscore) system. The random forest algorithm was applied to identify the TACE response-related core gene NDRG1 of HCC, and its role in the prognosis of HCC was explored. The role of NDRG1 in the progression and metastasis of HCC and functional mechanism were confirmed using several experimental methods. Results: Based on the GSE14520 and GSE104580 cohorts, we identified 2 TACE response-related molecular subtypes for HCC with significant differences in clinical features, and the TACE prognosis of Cluster A was significantly better than that of Cluster B (p < 0.0001). We then established the TRscore system and found that the low TRscore group showed a higher probability of survival and a lower rate of recurrence than the high TRscore group (p < 0.05) in both the HCC and TACE-treated HCC cohorts within the GSE14520 cohort. NDRG1 was determined to be the the hub gene associated with the TACE response of HCC and its high expression suggested a poor prognosis. Furthermore, The suppression of NDRG1 konckdown in tumorgenesis and metastasis of HCC was clarified in both vivo and vitro, which was importantly achieved through inducing ferroptosis in HCC cells, especially contributing to RLS3-induced ferroptosis. Conclusion: The constructed TACE response-related molecular subtypes and TRscores can specifically and accurately predict TACE prognosis for HCC. In addition, the TACE response-related hub gene NDRG1 may act as a guardian against ferroptosis to drive tumorgenesis and metastasis in HCC, which laid a new foundation for the development of new potential targeted therapy strategies to improve disease prognosis in HCC patients. [ABSTRACT FROM AUTHOR]
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- 2023
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25. Upregulation of the ferroptosi-srelated STEAP3 gene is a specific predictor of poor triple-negative breast cancer patient outcomes.
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Lifang Yuan, Jiannan Liu, Lei Bao, Huajun Qu, Jinyu Xiang, and Ping Sun
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TRIPLE-negative breast cancer ,CANCER prognosis ,GENE expression ,WESTERN immunoblotting ,DISEASE risk factors - Abstract
Objective: This study was designed to assess ferroptosis regulator gene (FRG) expression patterns in patients with TNBC based on data derived from The Cancer Genome Atlas (TCGA). Further, it was utilized to establish a TNBC FRG signature, after which the association between this signature and the tumor immune microenvironment (TIME) composition was assessed, and relevant prognostic factors were explored. Methods: The TCGA database was used to obtain RNA expression datasets and clinical information about 190 TNBC patients, after which a prognostic TNBCrelated FRG signature was established using a least absolute shrinkage and selection operator (LASSO) Cox regression approach. These results were validated with separate data from the Gene Expression Omnibus (GEO). The TNBC-specific prognostic gene was identified via this method. The STEAP3 was then validated through Western immunoblotting, immunohistochemical staining, and quantitative real-time polymerase chain reaction (RT-qPCR) analyses of clinical tissue samples and TNBC cell lines. Chemotherapy interactions and predicted drug sensitivity studies were investigated to learn more about the potential clinical relevance of these observations. Results: These data revealed that 87 FRGs were differentially expressed when comparing TNBC tumors and healthy tissue samples (87/259, 33.59%). Seven of these genes (CA9, CISD1, STEAP3, HMOX1, DUSP1, TAZ, HBA1) are significantly related to the overall survival of TNBC patients. Kaplan-Meier analyses and established FRG signatures and nomograms identified CISD1 and STEAP3 genes of prognostic relevance. Prognostic Risk Score values were positively correlated with the infiltration of CD4+ T cells (p = 0.001) and myeloid dendritic cells (p =0.004). Further evidence showed that STEAP3 was strongly and specifically associated with TNBC patient OS (P<0.05). The results above were confirmed by additional examinations of STEAP3 expression changes in TNBC patient samples and cell lines. High STEAP3 levels were negatively correlated with half-maximal inhibitory concentration (IC50) values for GSK1904529A (IGF1R inhibitor), AS601245 (JNK inhibitor), XMD8-85 (Erk5 inhibitor), Gefitinib, Sorafenib, and 5-Fluorouracil (P <0.05) in patients with TNBC based on information derived from the TCGA-TNBC dataset. Conclusion: In the present study, a novel FRG model was developed and used to forecast the prognosis of TNBC patients accurately. Furthermore, it was discovered that STEAP3 was highly overexpressed in people with TNBC and associated with overall survival rates, laying the groundwork for the eventually targeted therapy of individuals with this form of cancer. [ABSTRACT FROM AUTHOR]
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- 2023
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26. Inferring microenvironmental regulation of gene expression from single-cell RNA sequencing data using scMLnet with an application to COVID-19
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Zhongdao Wu, Xiaoqiang Sun, Jinyu Cheng, and Ji Zhang
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Cell ,Gene regulatory network ,Datasets as Topic ,Computational biology ,Biology ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Single-cell analysis ,Gene expression ,medicine ,Extracellular ,Humans ,Molecular Biology ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,Sequence Analysis, RNA ,COVID-19 ,medicine.anatomical_structure ,Gene Expression Regulation ,Cytokines ,Angiotensin-Converting Enzyme 2 ,Single-Cell Analysis ,Signal transduction ,030217 neurology & neurosurgery ,Information Systems - Abstract
Inferring how gene expression in a cell is influenced by cellular microenvironment is of great importance yet challenging. In this study, we present a single-cell RNA-sequencing data based multilayer network method (scMLnet) that models not only functional intercellular communications but also intracellular gene regulatory networks (https://github.com/SunXQlab/scMLnet). scMLnet was applied to a scRNA-seq dataset of COVID-19 patients to decipher the microenvironmental regulation of expression of SARS-CoV-2 receptor ACE2 that has been reported to be correlated with inflammatory cytokines and COVID-19 severity. The predicted elevation of ACE2 by extracellular cytokines EGF, IFN-γ or TNF-α were experimentally validated in human lung cells and the related signaling pathway were verified to be significantly activated during SARS-COV-2 infection. Our study provided a new approach to uncover inter-/intra-cellular signaling mechanisms of gene expression and revealed microenvironmental regulators of ACE2 expression, which may facilitate designing anti-cytokine therapies or targeted therapies for controlling COVID-19 infection. In addition, we summarized and compared different methods of scRNA-seq based inter-/intra-cellular signaling network inference for facilitating new methodology development and applications.
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- 2020
27. L-Ascorbic Acid 2-Phosphate Attenuates Methylmercury-Induced Apoptosis by Inhibiting Reactive Oxygen Species Accumulation and DNA Damage in Human SH-SY5Y Cells.
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Zuo, Kuiyang, Xu, Qi, Wang, Yujie, Sui, Yutong, Niu, Ye, Liu, Zinan, Liu, Mingsheng, Liu, Xinpeng, Liu, Dan, Sun, Wei, Wang, Ziyu, Liu, Xiaomei, and Liu, Jinyu
- Subjects
REACTIVE oxygen species ,HUMAN DNA ,GENE expression ,VITAMIN C ,APOPTOSIS - Abstract
Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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28. CircKRT14 upregulates E2F3 by interacting with miR-1256 to act as an oncogenic factor in esophageal cancer.
- Author
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Guan, Xingzhuo, Lan, Tingzhu, Wang, Yuanshi, Cui, Yan, Duan, Jinyu, and Xu, Hongjun
- Subjects
CIRCULAR RNA ,DISEASE progression ,REVERSE transcriptase polymerase chain reaction ,FLOW cytometry ,IN vitro studies ,BIOLOGICAL models ,IN vivo studies ,XENOGRAFTS ,WESTERN immunoblotting ,CANCER invasiveness ,ONCOGENES ,ANIMAL experimentation ,MICRORNA ,APOPTOSIS ,CELL motility ,GENE expression ,CELL proliferation ,DESCRIPTIVE statistics ,TRANSCRIPTION factors ,ESOPHAGEAL tumors ,MICE - Abstract
Background: A growing number of studies have focused on the regulatory role of circular RNAs (circRNAs) in a variety of cancers. The purpose of this study was to investigate the effect of circRNA Keratin 14 (circKRT14) on the progression of esophageal cancer (EC). Methods: The levels of circKRT14, miR-1256 and E2F transcription factor 3 (E2F3) were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot. The circular structure of circKRT14 was confirmed by RNase R digestion assay. Cell apoptosis, migration and invasion were detected by flow cytometry and transwell assay. The protein levels of related factors were determined by western blot. The relationship between miR-1256 and circKRT14 or E2F3 was verified by dual-luciferase reporter assay. The in vivo function of circKRT14 was studied by xenograft tumor assay. Results: CircKRT14 was significantly increased in EC tissues and cells. CircKRT14 silencing inhibited EC cell proliferation, migration, and invasion, but promoted EC cell apoptosis in vitro. CircKRT1 acted as a sponge for miR-1256 in EC, and in-miR-1256 abolished the inhibitory effect of circKRT14 suppression on EC cell progression. E2F3 was a target of miR-1256 and functioned as an oncogene in EC cells. MiR-1256 curbed EC progression by downregulating E2F3. CircKRT14 could affect E2F3 expression by targeting miR-1256. CircKRT14 regulated EC progression in vivo through miR-1256/E2F3 axis. Conclusions: These results uncovered that circKRT14 up-regulated the expression of E2F3 and promoted the malignant development of EC through sponging miR-1256. [ABSTRACT FROM AUTHOR]
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- 2023
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29. miR-4443/MMP2 suppresses the migration and invasion of trophoblasts through the HB-EGF/EGFR pathway in preeclampsia.
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Chen, Chao, Gao, Jing, Chen, Dan, Liu, Jinyu, He, Biwei, Chen, Yan, Zhang, Huijuan, Yang, Xingyu, and Cheng, Weiwei
- Subjects
PREECLAMPSIA ,GENE expression ,POTENTIAL functions ,PREGNANCY proteins ,TROPHOBLAST ,CELL migration - Abstract
Preeclampsia (PE) is a pregnancy-associated disease that may cause maternal and fetal morbidity and mortality. The dysregulation of microRNAs (miRNAs) and their potential functions has been an important direction for elucidating the mechanism of preeclampsia in recent years. The present study investigated whether miR-4443 was significantly increased in the placentas of severe preeclamptic patients, and the upregulation of miR-4443 inhibited the migration and invasion of HTR-8/SVneo cells according to transwell assays. Matrix metallopeptidase 2 (MMP2), which is involved in the degradation of extracellular matrix (ECM) components and harbors a miR-4443-binding site within its 3'-UTR as confirmed by a luciferase reporter assay, was identified to be directly inhibited by miR-4443. Moreover, siRNA targeting MMP2 imitated the effects of overexpressed miR-4443 on HTR-8/SVneo cell invasion and migration, whereas rescue experiments showed that MMP2 reversed this inhibitory function of miR-4443. Heparin-binding EGF-like growth factor (HB-EGF), as the downstream gene of MMP2, plays an important role in trophoblast invasion, and we confirmed that the expression of HB-EGF/EGFR pathway-related biomolecules was consistent with MMP2 influenced by upregulating and downregulating miR-4443 and that activated EGFR further transmitted intracellular downstream signaling via the MAPK pathway according to western blot assay. In conclusion, we demonstrated that miR-4443 suppresses the migration and invasion of trophoblasts, and its inhibitory effects are at least partially mediated by the suppression of MMP2. This inhibition might further affect the progression of preeclampsia through the HB-EGF/EGFR pathway, thus providing a new clue on the role of miR-4443 in the pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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30. Effects of Tributyrin Supplementation on Liver Fat Deposition, Lipid Levels and Lipid Metabolism-Related Gene Expression in Broiler Chickens.
- Author
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Gu, Tiantian, Duan, Mingcai, Liu, Jinyu, Chen, Li, Tian, Yong, Xu, Wenwu, Zeng, Tao, and Lu, Lizhi
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TRIBUTYRIN ,BROILER chickens ,FATTY acid synthases ,HDL cholesterol ,LIPOPROTEIN lipase - Abstract
The objective of this study was to investigate the effects of tributyrin supplementation on liver fat metabolism in broiler chickens. Two hundred and forty broilers were randomly allocated into two experimental groups (6 replicates per treatment; 20 chickens in each replicate): the control group (CN), which received a basal diet, and the tributyrin group (TB), which received a basal diet supplemented with 1 g/kg of tributyrin. The experimental period lasted 37 days. The results showed that in the liver, broilers supplemented with tributyrin had higher content of high-density lipoprotein cholesterol (HDL-C) (p < 0.05). Liver hepatic lipase (HL), lipoprotein lipase (LPL) and total lipid (TL) activity were significantly lower than in the TB group than that in the NC group. Meanwhile, the diet supplemented with tributyrin had more lipid droplets than the NC group, whereas the TB and NC groups showed no histological abnormalities in the liver. Furthermore, the mRNA expression levels of peroxisome proliferators-activated receptor α (PPARα), proliferators-activated receptor γ (PPARγ), fatty acid synthase (FAS), LPL and adipose triglyceride lipase (ATGL) in the liver were significantly upregulated in the TB group (p < 0.05), while those of the long-chain acyl-CoA-synthetase 1 (ACSL1) mRNA between the TB group and the NC group were not different (p > 0.05). These findings indicated that the diet supplemented with tributyrin could increase fat deposition appropriately by promoting fat synthesis without causing liver tissue damage, which demonstrated that tributyrin can be considered a valid feed additive for broiler chickens. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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31. The role of uhpA in Edwardsiella piscicida and the inflammatory cytokine response in tilapia
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Xuepeng Wang, Jinjing Huang, Jinyu Liu, Yongcan Sun, Jiakang Chen, and Tingqi Ye
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0301 basic medicine ,food.ingredient ,Virulence ,Spleen ,Aquatic Science ,Gene Mutant ,Biology ,Microbiology ,Fish Diseases ,03 medical and health sciences ,food ,Bacterial Proteins ,parasitic diseases ,Gene expression ,medicine ,Animals ,Environmental Chemistry ,Gene ,Inflammation ,Regulation of gene expression ,Enterobacteriaceae Infections ,Tilapia ,04 agricultural and veterinary sciences ,General Medicine ,DNA-Binding Proteins ,030104 developmental biology ,medicine.anatomical_structure ,Edwardsiella ,040102 fisheries ,Cytokines ,0401 agriculture, forestry, and fisheries ,Tumor necrosis factor alpha - Abstract
Edwardsiella piscicida (E. piscicida) is an important zoonotic pathogen that infects fish by colonizing the intestines. The intestine provides nutrition including Glucose 6-phosphate (Glu6P) and a competitive environment for the microbiota. Although the transport system regulatory protein gene uhpA has been reported in E. piscicida genomes, whether the uhpA gene is involved in the pathogenicity of E. piscicida remains largely unknown. Therefore, the uhpA gene mutants strain E. piscicida ΔuhpA was constructed to elucidate the functions of Glu6P and the uhpA gene in E. piscicida. The results demonstrated that Glu6P significantly increased the gene expression of uhpC/uhpB/uhpA than without adding Glu6P in the culture. The gene expression of uhpC and uhpB was down regulated in the mutant strain than that of in the wild type strain. E. piscicida ΔuhpA exhibited an increase in virulence compared to that of E. piscicida EIB202 [LD50 value: (3.98 × 106 CFU/fish) and LD50 value: (1.45 × 107 CFU/fish) respectively]. Besides, although TNF-α did not show significant differences (p > 0.05) in the spleen of tilapia infected with ΔuhpA and EIB202 in the whole observed period, the gene expression of IL-1β and TGF-β in the spleen of tilapia infected with ΔuhpA showed significantly higher (p
- Published
- 2020
32. Examination of methionine stimulation of gene expression in dairy cow mammary epithelial cells using RNA-sequencing
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Xiaoming Hou, Minghui Jiang, Feng Zhao, Ye Lin, Shuyuan Song, and Jinyu Zhou
- Subjects
Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Mammary Glands, Animal ,Methionine ,0302 clinical medicine ,Downregulation and upregulation ,Lactation ,Gene expression ,medicine ,Animals ,KEGG ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Keratin-18 ,Sequence Analysis, RNA ,Caseins ,RNA ,Epithelial Cells ,General Medicine ,Milk Proteins ,Cell biology ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,030220 oncology & carcinogenesis ,Cattle ,Female ,Animal Science and Zoology ,Rap1 ,Signal transduction ,Transcriptome ,Signal Transduction ,Food Science - Abstract
In this research communication, a cell model with elevated β-CASEIN synthesis was established by stimulating bovine mammary epithelial cells with 0.6 mM methionine, and the genome-wide gene expression profiles of methionine-stimulated cells and untreated cells were investigated by RNA sequencing. A total of 458 differentially expressed genes (DEGs; 219 upregulated and 239 downregulated) were identified between the two groups. Gene Ontology (GO) analysis showed that the two highest-ranked GO terms in ‘molecular function’ category were ‘binding’ and ‘catalytic activity’, suggesting that milk protein synthesis in methionine-stimulated cells requires induction of gene expression to increase metabolic activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that within the ‘environmental information processing’ category, the subcategory that is most highly enriched for DEGs was ‘signal transduction’. cGMP-PKG, Rap1, calcium, cAMP, PI3K-AKT, MAPK, and JAK-STAT are the pathways with the highest number of DEGs, suggesting that these signaling pathways have potential roles in mediating methionine-induced milk protein synthesis in bovine mammary epithelial cells. This study provides valuable insights into the physiological and metabolic adaptations in cells stimulated with methionine. Understanding the regulation of this transition is essential for effective intervention in the lactation process.
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- 2020
33. Specificity and application of SOX2 antibody
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Ping Liu, Longqin Wei, Gonghe Li, Wende Wu, Lingkang Liu, Jinyu Wei, Qingbo Xing, Jianhong Pan, Xiaoming Xu, Lixia Wang, Pengxia Wang, and Xibang Zheng
- Subjects
Male ,prokaryotic expression ,Sox2 antibody ,chicken ,specificity ,Gene Expression ,Genetics and Molecular Biology ,Antibodies ,Avian Proteins ,03 medical and health sciences ,stomatognathic system ,SOX2 ,Antigen ,Testis ,Animals ,Induced pluripotent stem cell ,Lung ,lcsh:SF1-1100 ,030304 developmental biology ,0303 health sciences ,biology ,Gene Expression Profiling ,SOXB1 Transcription Factors ,fungi ,0402 animal and dairy science ,Brain ,04 agricultural and veterinary sciences ,General Medicine ,040201 dairy & animal science ,Fusion protein ,Molecular biology ,histochemistry ,Organ Specificity ,Polyclonal antibodies ,Cerebellar cortex ,embryonic structures ,biology.protein ,Immunohistochemistry ,Animal Science and Zoology ,lcsh:Animal culture ,Rabbits ,sense organs ,biological phenomena, cell phenomena, and immunity ,Antibody ,Chickens - Abstract
Sox2 is known to play an important role in maintaining the totipotency and self-renewal of embryonic stem cells. The purpose of this study was to prepare an anti-chicken Sox2 polyclonal antibody using prokaryotic expression techniques, to evaluate its specificity and to use it to investigate the expression and distribution of Sox2 in the chicken brain and lungs. The chicken Sox2 gene was amplified and subcloned to a pET-30a vector to construct a prokaryotic expression vector, pET-Sox2. A His-Sox2 fusion protein was expressed, purified, and used to prepare an antichicken Sox2 polyclonal antibody. Western blotting revealed that the antichicken Sox2 antibody could specifically bind not only to the purified His-Sox2 fusion protein but also to the endogenous Sox2 protein in the testes of chicken, showing a distinct dose-dependent relationship between antigen and Sox2 antibody. Indirect immunofluorescent staining of Sox2-overexpressing cells showed strong nuclear and diffuse cytoplasmic immunoreactivity for Sox2 in the antichicken Sox2 antibody-staining cells. A CRISPR/Cas9 effector system-mediated Sox2 knockdown assay indicated that Sox2 expression in HEK 293T cells was downregulated in the presence of doxycycline but upregulated in the absence of doxycycline. In addition, cryosectioning and immunohistochemical staining illustrated that most spermatogonia in the seminiferous tubules, and a small number of Sertoli and Leydig cells, were positive for Sox2. The antichicken Sox2 antibody was also successfully used to investigate the expression and distribution of Sox2 in the chicken cerebellar cortex, optic tectum, cerebral cortex, and lungs. The results of this study confirmed the specificity of the antichicken Sox2 polyclonal antibody, which will be available for the study of biological functions of the chicken Sox2 gene and the self-renewal mechanisms of chicken pluripotent stem cells.
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- 2020
34. Nutrigenomic Role of Acetate and β-Hydroxybutyrate in Bovine Mammary Epithelial Cells
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Xiaoming Hou, Minghui Jiang, Feng Zhao, Ye Lin, Shuyuan Song, and Jinyu Zhou
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Adipose tissue ,Acetates ,Small molecule biosynthetic process ,Steroid biosynthesis ,Biology ,Transcriptome ,Mammary Glands, Animal ,Nutrigenomics ,Gene expression ,Genetics ,Animals ,Molecular Biology ,Cells, Cultured ,3-Hydroxybutyric Acid ,Gene Expression Profiling ,Fatty Acids ,Epithelial Cells ,Lipid metabolism ,Cell Biology ,General Medicine ,Milk ,Biochemistry ,Lipid biosynthetic process ,Cattle ,Female ,Steroid biosynthetic process - Abstract
Acetate and β-hydroxybutyrate (BHBA) are the predominant substrates for de novo fatty acid (FA) synthesis in mammary gland of dairy cow. To investigate the nutrigenomic role of acetate and BHBA in bovine mammary epithelial cells during milk fat production, RNA sequencing (RNA-seq) transcriptomic analysis was used to identify differentially expressed genes (DEGs) between acetate- and BHBA-treated cells (high-milk fat cells) and control cells. A total of 625 DEGs (358 upregulated and 267 downregulated) were identified between the high-milk fat cells and control cells. Gene ontology enrichment analysis revealed that the upregulated genes in high-milk fat cells were mainly involved in lipid biosynthetic process, steroid biosynthetic process, oxidation-reduction process, receptor binding, and vesicle and small molecule biosynthetic process. The downregulated genes were mainly associated with immune response, cytokine production, negative regulation of biological process, and peptidyl-threonine modification. Pathway analysis indicated that FA metabolism and steroid biosynthesis were significantly enriched for the upregulated genes in the high-milk fat cells, while apoptosis was enriched for the downregulated genes. This work provides a profile of gene expression changes that occur during acetate- and BHBA-induced milk fat synthesis in bovine mammary epithelial cells, which furthers our understanding of the molecular regulation of lipid metabolism.
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- 2020
35. Research Note: Correlation analysis of interleukin-6, interleukin-8, and C-C motif chemokine ligand 2 gene expression in chicken spleen and cecal tissues after Eimeria tenella infection in vivo
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Jinyu Wang, Guojun Dai, Genxi Zhang, Kaizhou Xie, Wenbin Zou, Xiaohui Wang, Tao Zhang, Hailiang Yu, and Huiqiang Shi
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Chemokine ,correlation analysis ,Spleen ,Ligands ,Eimeria ,Avian Proteins ,03 medical and health sciences ,Cecum ,Gene expression ,medicine ,Animals ,Interleukin 8 ,Interleukin 6 ,Chemokine CCL2 ,Poultry Diseases ,030304 developmental biology ,lcsh:SF1-1100 ,cecum ,0303 health sciences ,biology ,Coccidiosis ,Interleukin-6 ,Interleukin-8 ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,General Medicine ,Immunology, Health and Disease ,biology.organism_classification ,medicine.disease ,040201 dairy & animal science ,Molecular biology ,medicine.anatomical_structure ,biology.protein ,gene expression ,Animal Science and Zoology ,spleen ,lcsh:Animal culture ,Eimeria tenella - Abstract
IL-6, IL-8, and C-C motif chemokine ligand 2 (CCLi2) are important factors in inflammatory and immune responses. To investigate their relationships in the spleen and cecum and between coccidiosis-infected and uninfected states, we performed quantitative real-time PCR to compare the relative expression difference of IL-6, IL-8, and CCLi2 in the same tissues between the infection and control groups. In addition, the correlations of the relative expression levels of these 3 genes were determined in the same and different tissues within the same group. The results showed that the expression levels of IL-6, IL-8, and CCLi2 in the spleen and cecum of the infected group were all higher than those of the uninfected group (P < 0.05). The correlation coefficients among the IL-6, IL-8, and CCLi2 expression levels in the spleen or cecum were all positive in both the infection and control groups. In the spleen tissues, CCLi2 expression was strongly correlated with IL-6 and IL-8 in the uninfected group (P < 0.01), and the correlation coefficients reached 0.853 (R2 = 0.728) and 0.996 (R2 = 0.992), respectively. The expression of CCLi2 was also strongly correlated with IL-8 (R reached 0.890, R2 = 0.792) in the infected group. In the cecal tissues, the expression levels of the 3 genes were all extremely significantly correlated in the uninfected group (P < 0.01), and the correlation coefficients ranged from 0.498 to 0.765, indicating moderate correlations. The expression of IL-6 was extremely significantly positively correlated with IL-8 and CCLi2 in the infected group (P < 0.01), with moderate correlations (R ranged from 0.469–0.639). In addition, the expression levels of the 3 genes were not significantly correlated (P > 0.05) between the spleen and cecum tissues in either the infection group or the control group. These results indicate that IL-6, IL-8, and CCLi2 were correlated and play an important role in coccidiosis infection of Jinghai yellow chicken. Our data also provide a basis for further exploring the role of these 3 genes in genetic breeding for coccidiosis resistance.
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- 2020
36. Genome-wide identification of cold responsive transcription factors in Brassica napus L
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Liping Ke, Dongliang Yu, Jinhua Cheng, Lei Weixia, Janfang Gao, Weiguang Yang, Jinyu Wang, Zhixiong Fan, and Yuqiang Sun
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0106 biological sciences ,0301 basic medicine ,Short day ,Brassica ,Plant Science ,Biology ,01 natural sciences ,Genome ,Transcriptome ,03 medical and health sciences ,lcsh:Botany ,Gene expression ,Gene ,Transcription factor ,Cold stress ,Plant Proteins ,Genetics ,Ecotype ,Cold-Shock Response ,Brassica napus ,food and beverages ,biology.organism_classification ,lcsh:QK1-989 ,030104 developmental biology ,Genome, Plant ,010606 plant biology & botany ,Research Article ,Transcription Factors - Abstract
Background Cold stress is one of the primary environmental factors that affect plant growth and productivity, especially for crops like Brassica napus that live through cold seasons. Till recently, although a number of genes and pathways involved in B. napus cold response have been revealed by independent studies, a genome-wide identification of the key regulators and the regulatory networks is still lack. In this study, we investigated the transcriptomes of cold stressed semi-winter and winter type rapeseeds in short day condition, mainly with the purpose to systematically identify the functional conserved transcription factors (TFs) in cold response of B. napus. Results Global modulation of gene expression was observed in both the semi-winter type line (158A) and the winter type line (SGDH284) rapeseeds, in response to a seven-day chilling stress in short-day condition. Function analysis of differentially expressed genes (DEGs) revealed enhanced stresses response mechanisms and inhibited photosynthesis in both lines, as well as a more extensive inhibition of some primary biological processes in the semi-winter type line. Over 400 TFs were differentially expressed in response to cold stress, including 56 of them showed high similarity to the known cold response TFs and were consistently regulated in 158A and SGDH284, as well as 25 TFs which targets were over-represented in the total DEGs. A further investigation based on their interactions indicated the critical roles of several TFs in cold response of B. napus. Conclusion In summary, our results revealed the alteration of gene expression in cold stressed semi-winter and winter ecotype B. napus lines and provided a valuable collection of candidate key regulators involved in B. napus response to cold stress, which could expand our understanding of plant stress response and benefit the future improvement of the breed of rapeseeds.
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- 2020
37. Trp53 null and R270H mutant alleles have comparable effects in regulating invasion, metastasis, and gene expression in mouse colon tumorigenesis
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Ying Feng, Jinyu Tang, Naoya Sakamoto, Megan Green, Maranne Green, Kathleen R. Cho, Eric R. Fearon, Yuki E. Kurosu, Rork Kuick, and Jeffry Lin
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p53 ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,Carcinogenesis ,Adenomatous polyposis coli ,mouse model ,gain of function ,Mutant ,Mutation, Missense ,Gene Expression ,Mice, Transgenic ,Adenocarcinoma ,Biology ,medicine.disease_cause ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Mutant protein ,medicine ,Animals ,Humans ,Missense mutation ,Neoplasm Invasiveness ,tumor suppressor gene ,Neoplasm Metastasis ,Allele ,Molecular Biology ,Cell Biology ,Null allele ,digestive system diseases ,030104 developmental biology ,colon cancer ,loss of function ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,biology.protein ,KRAS ,Tumor Suppressor Protein p53 ,Colorectal Neoplasms - Abstract
Somatic APC (adenomatous polyposis coli), TP53, KRAS mutations are present in roughly 80%, 60%, and 40%, respectively, of human colorectal cancers (CRCs). Most TP53 mutant alleles in CRCs encode missense mutant proteins with loss-of-function (LOF) of p53’s transcriptional activity and dominant negative (DN) effects on wild-type p53 function. Missense mutant p53 proteins have been reported to exert gain-of-function (GOF) effects in cancer. We compared the phenotypic effects of the common human cancer-associated TP53 R273H missense mutation to p53 null status in a genetically engineered mouse CRC model. Inactivation of one allele of Apc together with activation of a Kras mutant allele in mouse colon epithelium instigated development of serrated and hyperplastic epithelium and adenomas (AK mice). Addition of a Trp53R270H or Trp53null mutant allele to the model (AKP mice) led to markedly shortened survival and increased tumor burden relative to that of AK mice, including adenocarcinomas in AKP mice. Comparable life span and tumor burden were seen in AKP mice carrying Trp53R270H or Trp53null alleles, along with similar frequencies of spontaneous metastasis to lymph nodes, lung, and liver. The fraction of adenocarcinomas with submucosa or deeper invasion was higher in AKP270/fl mice than in AKPfl/fl mice, but the incidence of adenocarcinomas per mouse did not differ significantly between AKPfl/fl and AKP270/fl mice. In line with their comparable biological behaviors, mouse primary tumors and tumor-derived organoids with the Trp53R270H or Trp53null alleles had highly similar gene expression profiles. Human CRCs with TP53 R273 missense mutant or null alleles also had essentially homogeneous gene expression patterns. Our findings indicate the R270H/R273H p53 mutant protein does not manifest definite GOF biological effects in mouse and human CRCs, suggesting possible GOF effects of mutant p53 in cancer phenotypes are likely allele-specific and/or context-dependent.
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- 2019
38. Promoter CAG is more efficient than hepatocyte‑targeting TBG for transgene expression via rAAV8 in liver tissues
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Jinyu Kang, Xie Zhang, Wentao Zheng, Yufei Song, Jia Luo, Aiming Liu, and Lujie Hang
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Male ,China ,Cancer Research ,Thyroxine-Binding Globulin ,Transgene ,Genetic Vectors ,Gene Expression ,Gene delivery ,Biochemistry ,Immediate-Early Proteins ,Green fluorescent protein ,Mice ,Thyroxine-binding globulin ,Transduction, Genetic ,Gene expression ,Genetics ,Animals ,Transgenes ,Promoter Regions, Genetic ,Enhancer ,Antigens, Viral ,Molecular Biology ,Gene ,Mice, Inbred ICR ,biology ,Chemistry ,Promoter ,Dependovirus ,Molecular biology ,Actins ,Gene Expression Regulation ,Liver ,Oncology ,Hepatocytes ,biology.protein ,Molecular Medicine - Abstract
The recombinant adeno‑associated virus 8 (rAAV8) vector is a widely used tool in basic research and clinical trials. The cytomegalovirus immediate‑early enhancer/chicken β‑actin (CAG) promoter is a synthetic promoter used in adenoviral constructs with a wide spectrum and notable efficiency. The thyroxine binding globulin (TBG) promoter is a liver‑specific promoter, which directs transgene expression in hepatocytes. However, the transduction efficiency of the rAAV vector is dependent on both the administration routes and the promoter elements. In the present study, the transduction efficiency in the liver following intraperitoneal (IP) and intravenous (IV) injections of rAAV8 with the CAG, TBG669 and TBG410 promoters was compared. Enhanced green fluorescent protein (EGFP) expression was used as the biomarker to indicate efficiency. Among the three different promoters, CAG exhibited the highest efficiency from both IV and IP injections. Following IV administration, EGFP expression, induced by the CAG promoter, was 67‑fold higher compared with that in the TBG410 promoter group and 26‑fold higher compared with that in the TBG669 promoter group. EGFP protein expression was higher with IV injection compared with that for IP injection for both the CAG and TBG669 promoters (P
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- 2021
39. NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by regulating the NF-κB and MAPK pathways
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He Nan, Xin Zhang, Jinyu Liu, and Jialong Guo
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MAPK/ERK pathway ,p38 mitogen-activated protein kinases ,Clinical Biochemistry ,Immunology ,Gene Expression ,Inflammation ,Proinflammatory cytokine ,Arthritis, Rheumatoid ,chemistry.chemical_compound ,Downregulation and upregulation ,medicine ,Immunology and Allergy ,Humans ,Phosphorylation ,Cells, Cultured ,Gene knockdown ,Intracellular Signaling Peptides and Proteins ,NF-kappa B ,NF-κB ,Synoviocytes ,chemistry ,Gene Knockdown Techniques ,Cancer research ,Cytokines ,medicine.symptom ,Inflammation Mediators ,Mitogen-Activated Protein Kinases ,Biomarkers ,Signal Transduction - Abstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by abnormal synovial hyperplasia and the release of inflammatory cytokines. NLRP12 is a member of the family nod-like receptor (NLR) families that are activators of inflammation. However, the role of NLRP12 in fibroblast-like synoviocytes (FLSs) is still unclear. In the present study, we have investigated the role of NLRP12 in fibroblast-like synoviocytes (FLSs). The results demonstrated that NLRP12 overexpression inhibited proliferation and promoted cell apoptosis in RA-FLSs. Moreover, NLRP12 overexpression repressed inflammation by downregulation of IL-1β, TNF-α, IL-6, IFN-γ and MCP-1 production and upregulation of IL-10 levels with knockdown of NLRP12 expression showing opposite effects. In addition, NLRP12 overexpression suppressed phosphorylation of JNK, ERK, p38 and NF-κB in RA-FLSs, whereas NLRP12 knockdown promoted phosphorylation of these proteins. In conclusion, these findings demonstrate that NLRP12 inhibits proliferation and inflammation of RA-FLSs via the regulation of the NF-κB and MAPK signaling pathways, suggesting that NLRP12 might be a potential target for RA treatment.
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- 2021
40. Transcriptome Analysis of Differentially Expressed mRNA Related to Pigeon Muscle Development
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Lan Chen, Hao Ding, Yueyue Lin, Tao Zhang, Guojun Dai, Genxi Zhang, Jinyu Wang, and Kaizhou Xie
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Messenger RNA ,General Veterinary ,WGCNA ,Veterinary medicine ,Skeletal muscle ,MYPN ,Biology ,Article ,Cell biology ,Transcriptome ,pigeon ,transcriptomics ,medicine.anatomical_structure ,QL1-991 ,Gene expression ,SF600-1100 ,OGDH ,medicine ,Animal Science and Zoology ,skeletal muscle ,development and growth ,Gene ,Zoology ,PI3K/AKT/mTOR pathway - Abstract
Simple Summary The growth and development of skeletal muscle determine the meat production performance of pigeons and are regulated by complex gene networks. To explore the genes involved in regulating the growth and development of pigeon skeletal muscle, RNA sequencing (RNA−seq) was used to characterise gene expression profiles during the development and growth of pigeon breast muscle and identify differentially expressed genes (DEGs) among different stages. This study expanded the diversity of pigeon mRNA, and it was helpful to understand the role of mRNA in pigeon muscle development and growth. Abstract The mechanisms behind the gene expression and regulation that modulate the development and growth of pigeon skeletal muscle remain largely unknown. In this study, we performed gene expression analysis on skeletal muscle samples at different developmental and growth stages using RNA sequencing (RNA−Seq). The differentially expressed genes (DEGs) were identified using edgeR software. Weighted gene co−expression network analysis (WGCNA) was used to identify the gene modules related to the growth and development of pigeon skeletal muscle based on DEGs. A total of 11,311 DEGs were identified. WGCNA aggregated 11,311 DEGs into 12 modules. Black and brown modules were significantly correlated with the 1st and 10th day of skeletal muscle growth, while turquoise and cyan modules were significantly correlated with the 8th and 13th days of skeletal muscle embryonic development. Four mRNA−mRNA regulatory networks corresponding to the four significant modules were constructed and visualised using Cytoscape software. Twenty candidate mRNAs were identified based on their connectivity degrees in the networks, including Abca8b, TCONS−00004461, VWF, OGDH, TGIF1, DKK3, Gfpt1 and RFC5, etc. A KEGG pathway enrichment analysis showed that many pathways were related to the growth and development of pigeon skeletal muscle, including PI3K/AKT/mTOR, AMPK, FAK, and thyroid hormone pathways. Five differentially expressed genes (LAST2, MYPN, DKK3, B4GALT6 and OGDH) in the network were selected, and their expression patterns were quantified by qRT−PCR. The results were consistent with our sequencing results. These findings could enhance our understanding of the gene expression and regulation in the development and growth of pigeon muscle.
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- 2021
41. The expression of cuproptosis-related genes in hepatocellular carcinoma and their relationships with prognosis.
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Xueying Zhao, Jin Chen, Shangqi Yin, Jingren Shi, Mei Zheng, Chaonan He, Huan Meng, Ying Han, Jinyu Han, Jingjing Guo, Zhengrong Yuan, and Yajie Wang
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CANCER prognosis ,GENE expression ,GENE expression profiling ,NOTCH signaling pathway ,KILLER cells ,BLEPHAROPTOSIS - Abstract
Background: The mechanism of cuproptosis has recently been reported in lipoylated proteins of the tricarboxylic acid (TCA) cycle. Besides, the role of copper was previously recognized in cancer progression. We evaluated the prognostic value of cuproptosis-related gene expression in hepatocellular carcinoma (HCC). Methods: Remarkable genes were selected both in differential expression analysis and Kaplan-Meier survival analysis from ninety-six cuproptosis-related genes using The Cancer Genome Atlas (TCGA) database. The relationships between clinical characteristics and gene expression were performed with Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression. Clinicopathologic factors correlated with overall survival in HCCs conducting univariate and multivariate Cox regression analysis. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Human Protein Atlas (HPA) databases were utilized to verify the results. Furthermore, Gene Set Enrichment Analysis (GSEA) identified the potential key pathways that dominate cuproptosis in HCC. Results: Elevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, LIPT1, DLAT, PDHA1, MTF1, ACPI, FDX2, NUBP2, CIAPIN1, ISCA2 and NDOR1 expression, as well as declined AOC1, FDX1, MT-CO1, and ACO1 expression were significantly emerged in HCC tumor tissues and were significantly associated with HCCs poor survival. The expressions of screened cuproptosis-related genes were prominently related to clinical features. GSEA analysis reported many key signaling pathways (such as natural killer cell mediated cytotoxicity, TCA cycle, glutathione metabolism, ATP-binding cassette (ABC) transporters, Notch signaling pathway, ErbB signaling pathway, and metabolism of xenobiotics by cytochrome p450) were differentially enriched in HCCs with varying degrees of cuproptosis-related genes expression. Conclusions: The twenty cuproptosis-related genes might be utilized as new candidate prognostic biomarkers for HCC. [ABSTRACT FROM AUTHOR]
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- 2022
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42. Oncogenic EFNA4 Amplification Promotes Lung Adenocarcinoma Lymph Node Metastasis.
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Zhao, Xiangyu, Chen, Yuxing, Sun, Xiaoqin, He, Zaoke, Wu, Tao, Wu, Chenxu, Chen, Jing, Wang, Jinyu, Diao, Kaixuan, and Liu, Xue-Song
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LUNG cancer prognosis ,DNA analysis ,ADENOCARCINOMA ,DISEASE progression ,ONCOGENES ,METASTASIS ,LYMPH nodes ,CELL physiology ,GENE expression ,CELL motility ,GENOTYPES ,MESSENGER RNA ,GENE amplification ,MEMBRANE proteins - Abstract
Simple Summary: Lymph nodes are likely to be the first stop for lung cancer metastasis. To further investigate the mechanism of lung cancer lymph node metastasis, we performed cancer genome analysis and found that EFNA4, a member of the ephrin (EPH) family, is amplified and up-regulated in lung tumor patients, especially in patients with lymph node metastases. In vitro and in vivo experiments show that overexpression of EFNA4 promotes lung tumor cell proliferation and migration, whereas knockdown or knockout of EFNA4 inhibits cell proliferation and migration. Altogether, our results suggest that the DNA amplification of the EFNA4 genome locus could play an oncogenic function in promoting lung cancer lymph node metastasis. Lymph nodes metastases are common in patients with lung cancer. Additionally, those patients are often at a higher risk for death from lung tumor than those with tumor-free lymph nodes. Somatic DNA alterations are key drivers of cancer, and copy number alterations (CNAs) are major types of DNA alteration that promote lung cancer progression. Here, we performed genome-wide DNA copy number analysis, and identified a novel lung-cancer-metastasis-related gene, EFNA4. The EFNA4 genome locus was significantly amplified, and EFNA4 mRNA expression was significantly up-regulated in lung cancer compared with normal lung tissue, and also in lung cancer with lymph node metastases compared with lung cancer without metastasis. EFNA4 encodes Ephrin A4, which is the ligand for Eph receptors. The function of EFNA4 in human lung cancer remains largely unknown. Through cell line experiments we showed that EFNA4 overexpression contributes to lung tumor cells growth, migration and adhesion. Conversely, EFNA4 knockdown or knockout led to the growth suppression of cells and tumor xenografts in mice. Lung cancer patients with EFNA4 overexpression have poor prognosis. Together, by elucidating a new layer of the role of EFNA4 in tumor proliferation and migration, our study demonstrates a better understanding of the function of the significantly amplified and overexpressed gene EFNA4 in lung tumor metastasis, and suggests EFNA4 as a potential target in metastatic lung cancer therapy. [ABSTRACT FROM AUTHOR]
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- 2022
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43. Mitochondrial Functions Are Compromised in CD4 T Cells From ART-Controlled PLHIV
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Ling Wang, Zheng D. Morrison, Bal Krishna Chand Thakuri, Juan Zhao, Lam Nhat Nguyen, Shunbin Ning, Zhengke Li, Xiao Y. Wu, Jinyu Zhang, Madison Schank, Mohamed El Gazzar, Zhi Q. Yao, Zeyuan Lu, Xindi Dang, Stella C. Ogbu, Dechao Cao, Lam Ngoc Thao Nguyen, Ying Liu, Jonathan P. Moorman, and Sushant Khanal
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0301 basic medicine ,CD4-Positive T-Lymphocytes ,Male ,senescence ,Gene Expression ,Apoptosis ,HIV Infections ,0302 clinical medicine ,Antiretroviral Therapy, Highly Active ,Immunology and Allergy ,Cells, Cultured ,Original Research ,T cell exhaustion ,medicine.diagnostic_test ,Middle Aged ,Viral Load ,Phenotype ,Cell biology ,Mitochondria ,DNA-Binding Proteins ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Senescence ,Adult ,immune non-responder ,T cell ,Immunology ,Biology ,Flow cytometry ,Mitochondrial Proteins ,03 medical and health sciences ,Young Adult ,Immune system ,Stress, Physiological ,mitochondrial dysfunction ,medicine ,Humans ,Psychological repression ,Aged ,HIV ,RC581-607 ,TFAM ,CD4 Lymphocyte Count ,030104 developmental biology ,HIV-1 ,Immunologic diseases. Allergy ,Biomarkers ,Transcription Factors - Abstract
The hallmark of HIV/AIDS is a gradual depletion of CD4 T cells. Despite effective control by antiretroviral therapy (ART), a significant subgroup of people living with HIV (PLHIV) fails to achieve complete immune reconstitution, deemed as immune non-responders (INRs). The mechanisms underlying incomplete CD4 T cell recovery in PLHIV remain unclear. In this study, CD4 T cells from PLHIV were phenotyped and functionally characterized, focusing on their mitochondrial functions. The results show that while total CD4 T cells are diminished, cycling cells are expanded in PLHIV, especially in INRs. HIV-INR CD4 T cells are more activated, displaying exhausted and senescent phenotypes with compromised mitochondrial functions. Transcriptional profiling and flow cytometry analysis showed remarkable repression of mitochondrial transcription factor A (mtTFA) in CD4 T cells from PLHIV, leading to abnormal mitochondrial and T cell homeostasis. These results demonstrate a sequential cellular paradigm of T cell over-activation, proliferation, exhaustion, senescence, apoptosis, and depletion, which correlates with compromised mitochondrial functions. Therefore, reconstituting the mtTFA pathway may provide an adjunctive immunological approach to revitalizing CD4 T cells in ART-treated PLHIV, especially in INRs.
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- 2021
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44. Selection and Verification of Appropriate Reference Genes for Expression Normalization in Cryptomeria fortunei under Abiotic Stress and Hormone Treatments
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Junjie Yang, Yingting Zhang, Jinyu Xue, Jiebing Cui, Lijuan Zhu, Hailiang Hu, and Jin Xu
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0106 biological sciences ,0301 basic medicine ,Cryptomeria fortunei ,abiotic stress ,reference gene ,Cryptomeria ,Computational biology ,QH426-470 ,Genes, Plant ,Real-Time Polymerase Chain Reaction ,01 natural sciences ,Salt Stress ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Plant Growth Regulators ,Gene Expression Regulation, Plant ,Reference genes ,Gene expression ,Genetics ,Gene ,Abscisic acid ,Genetics (clinical) ,hormone treatments ,Methyl jasmonate ,biology ,Abiotic stress ,Gene Expression Profiling ,Cupressaceae ,qRT-PCR ,Reference Standards ,biology.organism_classification ,different tissues ,030104 developmental biology ,chemistry ,Gibberellin ,Heat-Shock Response ,010606 plant biology & botany - Abstract
Cryptomeria fortunei has become one of the main timber afforestation species in subtropical high-altitude areas of China due to its fast growth, good material quality, and strong adaptability, showing broad application prospects. Quantitative real-time PCR (qRT-PCR) is the most accurate and widely used gene expression evaluation technique, and selecting appropriate reference genes (RGs) is essential for normalizing qRT-PCR results. However, suitable RGs for gene expression normalization in C. fortunei have not been reported. Here, we tested the expression stability for 12 RGs in C. fortunei under various experimental conditions (simulated abiotic stresses (cold, heat, drought, and salinity) and hormone treatments (methyl jasmonate, abscisic acid, salicylic acid, and gibberellin) and in different tissues (stems, tender needles, needles, cones, and seeds) using four algorithms (delta Ct, geNorm, NormFinder, and BestKeeper). Then, geometric mean rankings from these algorithms and the RefFinder program were used to comprehensively evaluate RG stability. The results indicated CYP, actin, UBC, and 18S as good choices for studying C. fortunei gene expression. qRT-PCR analysis of the expression patterns of three target genes (CAT and MAPK1/6) further verified that the selected RGs were suitable for gene expression normalization. This study provides an important basis for C. fortunei gene expression standardization and quantification.
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- 2021
45. Study on the transcriptome for breast muscle of chickens and the function of key gene RAC2 on fibroblasts proliferation
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Xinchao Zhang, Tingting Li, Genxi Zhang, Pengfei Wu, Cong Qiu, Kaizhou Xie, Jinyu Wang, Kaizhi Zhou, Tao Zhang, Guojun Dai, and Mingliang He
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Male ,lcsh:QH426-470 ,MAPK8 ,lcsh:Biotechnology ,Steroid biosynthesis ,Biology ,Small hairpin RNA ,Transcriptome ,03 medical and health sciences ,Jinghai yellow chicken ,0302 clinical medicine ,lcsh:TP248.13-248.65 ,Gene expression ,Genetics ,Animals ,KEGG ,Gene ,030304 developmental biology ,Biological Phenomena ,Cell Proliferation ,0303 health sciences ,Gene Expression Profiling ,Fibroblasts ,Growth and development ,Molecular biology ,Fold change ,lcsh:Genetics ,qPCR ,030220 oncology & carcinogenesis ,RNAi ,RNA-seq ,Chickens ,Biotechnology ,Research Article - Abstract
Background Growth performance is significant in broiler production. In the growth process of broilers, gene expression varies at different growth stages. However, limited research has been conducted on the molecular mechanisms of muscle growth and development in yellow-feathered male chickens. Results In the study, we used RNA-seq to study the transcriptome of the breast muscle of male Jinghai yellow chickens at 4 (M4F), 8 (M8F) and 12 weeks (M12F) of age. The results showed that 4608 differentially expressed genes (DEGs) were obtained by comparison in pairs of the three groups with Fold Change (FC) ≥ 2 and False Discovery Rate (FDR) ≤ 0.05, and 83, 3445 and 3903 DEGs were obtained separately from M4FvsM8F, M4FvsM12F and M8FvsM12F. Six genes were found as co-differentially expressed in the three age groups, namely SNCG, MYH1A, ARHGDIB, ENSGALG00000031598, ENSGALG00000035660 and ENSGALG00000030559. The GO analysis showed that 0, 304 and 408 biological process (BP) were significantly enriched in M4FvsM8F, M4FvsM12F and M8FvsM12F groups, respectively. KEGG pathway enrichment showed that 1, 2, 4 and 4 pathways were significantly enriched in M4FvsM8F, M4FvsM12F, M8FvsM12F and all DEGs, respectively. They were steroid biosynthesis, carbon metabolism, focal adhesion, cytokine-cytokine receptor interaction, biosynthesis of amino acids and salmonella infection. We constructed short hairpin RNA (shRNA) to interfere the differentially expressed gene RAC2 in DF-1 cells and detected mRNA and protein expression of the downstream genes PAK1 and MAPK8. Results of qPCR showed that RAC2, PAK1 and MAPK8 mRNA expression significantly decreased in the shRAC2–2 group compared with the negative control (NC) group. Western Blot (WB) results showed that the proteins of RAC2, PAK1 and MAPK8 also decreased in the shRAC2–2 group. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) assay both showed that the proliferation of DF-1 cells was significantly inhibited after transfection of shRAC2–2. Conclusions The results of RNA-seq revealed genes, BP terms and KEGG pathways related to growth and development of male Jinghai yellow chickens, and they would have important guiding significance to our production practice. Further research suggested that RAC2 might regulate cell proliferation by regulating PAKs/MAPK8 pathway and affect growth of chickens.
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- 2021
46. Change in Bitterness, Accumulation of Cucurbitacin B and Expression Patterns of CuB Biosynthesis-related Genes in Melon During Fruit Development
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Yang Xuhui, Zhang Qiaoling, Fu Jinyu, Liu Li, Hua Deping, and Meiting Xie
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Melon ,Fruit development ,Plant Science ,Horticulture ,Biology ,chemistry.chemical_compound ,Cucurbitacins ,Biochemistry ,Biosynthesis ,chemistry ,Gene expression ,Cultivar ,Cucurbitacin B ,Gene - Published
- 2019
47. Genome-wide identification of ubiquitin proteasome subunits as superior reference genes for transcript normalization during receptacle development in strawberry cultivars
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Meng Yuan, Aiying Zheng, Changmei Chen, Juanjuan Song, Li Zekun, Qingxi Chen, Guifeng Xie, Jianqing Chen, Tengyun Wang, Jinyu Zhou, Cheng Xiangyu, Yanhong Hong, and Yilin Zhang
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0106 biological sciences ,Proteasome Endopeptidase Complex ,lcsh:QH426-470 ,lcsh:Biotechnology ,Biology ,Proteomics ,Real-Time Polymerase Chain Reaction ,01 natural sciences ,Genome ,Strawberry ,Fragaria ,Transcriptome ,03 medical and health sciences ,lcsh:TP248.13-248.65 ,Reference genes ,Gene expression ,Genetics ,Ubiquitin 26S proteasome system ,Gene ,030304 developmental biology ,0303 health sciences ,Ubiquitin ,Gene Expression Profiling ,fungi ,Reference gene ,Reference Standards ,Housekeeping gene ,lcsh:Genetics ,Receptacle development ,DNA microarray ,010606 plant biology & botany ,Biotechnology ,Research Article - Abstract
Background Gene transcripts that show invariant abundance during development are ideal as reference genes (RGs) for accurate gene expression analyses, such as RNA blot analysis and reverse transcription–quantitative real time PCR (RT-qPCR) analyses. In a genome-wide analysis, we selected three “Commonly used” housekeeping genes (HKGs), fifteen “Traditional” HKGs, and nine novel genes as candidate RGs based on 80 publicly available transcriptome libraries that include data for receptacle development in eight strawberry cultivars. Results The results of the multifaceted assessment consistently revealed that expression of the novel RGs showed greater stability compared with that of the “Commonly used” and “Traditional” HKGs in transcriptome and RT-qPCR analyses. Notably, the majority of stably expressed genes were associated with the ubiquitin proteasome system. Among these, two 26 s proteasome subunits, RPT6A and RPN5A, showed superior expression stability and abundance, and are recommended as the optimal RGs combination for normalization of gene expression during strawberry receptacle development. Conclusion These findings provide additional useful and reliable RGs as resources for the accurate study of gene expression during receptacle development in strawberry cultivars.
- Published
- 2021
48. Using expression quantitative trait loci data and graph-embedded neural networks to uncover genotype-phenotype interactions.
- Author
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Xinpeng Guo, Jinyu Han, Yafei Song, Zhilei Yin, Shuaichen Liu, and Xuequn Shang
- Subjects
LOCUS (Genetics) ,ARTIFICIAL neural networks ,FEATURE selection ,DEEP learning ,GENE expression ,NOSOLOGY - Abstract
Motivation: A central goal of current biology is to establish a complete functional link between the genotype and phenotype, known as the socalled genotype-phenotype map. With the continuous development of high-throughput technology and the decline in sequencing costs, multiomics analysis has become more widely employed. While this gives us new opportunities to uncover the correlation mechanisms between singlenucleotide polymorphism (SNP), genes, and phenotypes, multi-omics still faces certain challenges, specifically: 1) When the sample size is large enough, the number of omics types is often not large enough to meet the requirements of multi-omics analysis; 2) each omics' internal correlations are often unclear, such as the correlation between genes in genomics; 3) when analyzing a large number of traits (p), the sample size (n) is often smaller than p, n << p, hindering the application of machine learning methods in the classification of disease outcomes. Results: To solve these issues with multi-omics and build a robust classification model, we propose a graph-embedded deep neural network (G-EDNN) based on expression quantitative trait loci (eQTL) data, which achieves sparse connectivity between network layers to prevent overfitting. The correlation within each omics is also considered such that the model more closely resembles biological reality. To verify the capabilities of this method, we conducted experimental analysis using the GSE28127 and GSE95496 data sets from the Gene Expression Omnibus (GEO) database, tested various neural network architectures, and used prior data for feature selection and graph embedding. Results show that the proposed method could achieve a high classification accuracy and easy-to-interpret feature selection. This method represents an extended application of genotype-phenotype association analysis in deep learning networks. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
49. Astaxanthin suppresses End MT by LOX-1 pathway in ox-LDL-induced HUVECs.
- Author
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Zhu, Zhongsheng, Li, Jinyu, Tong, Rui, Zhang, Xiaorong, and Yu, Bo
- Subjects
- *
ASTAXANTHIN , *GENE expression , *CELL survival , *SUPEROXIDE dismutase , *PROTEIN expression , *OXIDATIVE stress - Abstract
Introduction: Astaxanthin (ASX) is carotenoid with the highest antioxidant activity in various cell types and reverse atherosclerosis. However, the roles and detailed mechanisms of ASX in atherosclerosis associated endothelial injury remains unclear. Methods: In vitro atherosclerosis model was established in HUVECs by incubation with oxidized low-density lipoprotein (ox-LDL). Cell viability and oxidative stress were measured. The mRNA and protein expressions of lectin-like ox-LDL receptor (LOX-1) and other related genes were determined. Results: ox-LDL reduced cell viability of HUVECs, and induced oxidative stress, as evidenced by elevated cellular malondialdehyde (MDA) and decreased superoxide dismutase (SOD). Pretreatment with ASX (50, 100, 200, and 400 μM) markedly reversed the reduction in cell viability and an increase in migration of HUVECs induced by ox-LDL (50 μg/mL). ASX attenuated the increase in the endothelial-to-mesenchymal transition (EndMT) process, as evidenced by increased CD31 and decreased α-SMA and vimentin proteins by ASX treatment in HUVECs. Furthermore, ASX attenuated the increase in MDA and decrease in SOD induced by ox-LDL, increased supernatant NO production, attenuated the increase in iNOS and decrease in eNOS in HUVECs with ox-LDL. ASX enhanced mRNA and protein expressions of the lectin-like ox-LDL receptor (LOX-1), which was dependent on ASX's antioxidant activity. The inhibitory effect of ASX on EndMT could be abolished by overexpression of LOX-1 in HUVECs induced by ox-LDL. Conclusions: Our data speculate that ASX prevents ox-LDL-induced endothelial cell injury and EndMT by inducing antioxidant property (SOD and NO) and decreasing LOX-1 expression. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
50. Tet1 Regulates Astrocyte Development and Cognition of Mice Through Modulating GluA1
- Author
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Weize Xu, Xicheng Zhang, Feng Liang, Yuhang Cao, Ziyi Li, Wenzheng Qu, Jinyu Zhang, Yanhua Bi, Chongran Sun, Jianmin Zhang, Binggui Sun, Qiang Shu, and Xuekun Li
- Subjects
cognition ,QH301-705.5 ,RNA ,Cognition ,Cell Biology ,Ten eleven translocation ,Biology ,DNA sequencing ,Tet1 ,Cell biology ,Cell and Developmental Biology ,medicine.anatomical_structure ,astrocyte ,Gene expression ,medicine ,neuronal development ,Biology (General) ,Function (biology) ,GluA1 ,Developmental Biology ,Astrocyte ,Original Research - Abstract
Tet (Ten eleven translocation) family proteins-mediated 5-hydroxymethylcytosine (5hmC) is highly enriched in the neuronal system, and is involved in diverse biological processes and diseases. However, the function of 5hmC in astrocyte remains completely unknown. In the present study, we show that Tet1 deficiency alters astrocyte morphology and impairs neuronal function. Specific deletion of Tet1 in astrocyte impairs learning and memory ability of mice. Using 5hmC high-throughput DNA sequencing and RNA sequencing, we present the distribution of 5hmC among genomic features in astrocyte and show that Tet1 deficiency induces differentially hydroxymethylated regions (DhMRs) and alters gene expression. Mechanistically, we found that Tet1 deficiency leads to the abnormal Ca2+ signaling by regulating the expression of GluA1, which can be rescued by ectopic GluA1. Collectively, our findings suggest that Tet1 plays important function in astrocyte physiology by regulating Ca2+ signaling.
- Published
- 2020
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