MOLECULES
·
2023
·Vol. 28
·期 14
·5496
·
IF 4.6
Ting Li,Chaoyue Yang,Houkang Cao,Siyi Mo,Bo Li,Zhipeng Huang,Ruobing Zhang,Jianzhao Wu,Kefeng Zhang,Ya Gao
Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.Keywords:bergenin;isonicotinic acid hydrazide;rifampicin;liver injury;RNA sequencing
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AQUATIC TOXICOLOGY
·
2023
·
IF 4.5
Xin Li,Weiwei Wang,Xuedong Wang,Huili Wang
Herein, we demonstrated that sublethal-dose exposure to triclosan (TCS) and triclocarban (TCC) triggered larval zebrafish immunotoxicity. Acute exposure to TCS induced significant increases in larval neutrophils and macrophages and a prominent decrease in thymic T cells. In contrast, three kinds of cells (neutrophils, macrophages, and thymic T cells) were significantly reduced under TCC exposure, suggesting that both TCS and TCC suppress thymus development and mature T-cell differentiation. TCC was confirmed to have more severe immunotoxicity than TCS. Using Illumina RNA-Seq, 581 and 738 differentially expressed genes (DEGs) were identified in the TCS and TCC treatments, respectively. GO function and KEGG pathway enrichment analyses revealed that the DEGs were not identical in terms of biological processes, cellular components and molecular functions, but were primarily involved in immune response. KEGG analysis showed that approximately 47% and 11% of DEGs were mainly enriched in the immune system of the TCC and TCS treatments, respectively. Protein-protein interaction (PPI) network analysis confirmed that the hub genes enriched in the immune-related pathways differed between TCS and TCC exposure. The hub genes were fynb, mapk12b, scarb1, pik3r2, prkg3, srfa, arhgef2, cldn15la , and cldn15lb in the TCS treatment, and plg, serping1, masp2, fgg, vtnb, mmp9, serpine1, il1b, sb:cb37 and stat3 in the TCC treatment. Molecular docking simulation demonstrated that both TCS and TCC were stably docked with their target hub genes, and that their target molecules for inducing immunotoxicity were different. The differential target molecules and action pathways induced by TCS and TCC exposure provide us with diagnostic targets and toxicological endpoints.
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Genes
·
2023
·Vol. 14
·期 6
·1287
·
IF 3.5
Meng Chu,Yichao Qin,Xiuying Lin,Li Ma,Dehai Deng,Daizhu Lv,Pengcheng Fu,Huan Lin
The coconut (Cocos nuciferaL.) is a commercial crop widely distributed among coastal tropical regions. It provides millions of farmers with food, fuel, cosmetics, folk medicine, and building materials. Among these, oil and palm sugar are representative extracts. However, this unique living species ofCocoshas only been preliminarily studied at molecular levels. Benefiting from the genomic sequence data published in 2017 and 2021, we investigated the transfer RNA (tRNA) modifications and modifying enzymes of the coconut in this survey. An extraction method for the tRNA pool from coconut flesh was built. In total, 33 species of modified nucleosides and 66 homologous genes of modifying enzymes were confirmed using a nucleoside analysis using high-performance liquid chromatography combined with high-resolution mass spectrometry (HPLC-HRMS) and homologous protein sequence alignment. The positions of tRNA modifications, including pseudouridines, were preliminarily mapped using a oligonucleotide analysis, and the features of their modifying enzymes were summarized. Interestingly, we found that the gene encoding the modifying enzyme of 2′-O-ribosyladenosine at the 64th position of tRNA (Ar(p)64) was uniquely overexpressed under high-salinity stress. In contrast, most other tRNA-modifying enzymes were downregulated with mining transcriptomic sequencing data. According to previous physiological studies of Ar(p)64, the coconut appears to enhance the quality control of the translation process when subjected to high-salinity stress. We hope this survey can help advance research on tRNA modification and scientific studies of the coconut, as well as thinking of the safety and nutritional value of naturally modified nucleosides.Keywords:Cocos nucifera;epitranscriptomics;LC-MS/MS;nucleoside misidentification;RNA modification
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Materials Today Bio
·
2023
·
IF 8.2
Jiahao Wang,Peiyi Zhao,Zhirong Chen,Hui Wang,Yajia Wang,Quankui Lin
Fibrotic eye diseases, a series of severe oculopathy, that will destroy normal ocular refractive media and imaging structures. It is characterized by the transformation of the epithelial cells into mesenchyme cells. Proliferative vitreoretinopathy (PVR) is one of these representative diseases. In this investigation, polyethylene glycol grafted branched Polyethyleneimine (PEI- g -PEG) was used as a non-viral gene vector in gene therapy of PVR to achieve anti-fibroblastic effects in vitro and in vivo by interfering with platelet-derived growth factor alpha receptor (PDGFR-α) in the epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells. The plasmid was wrapped by electrostatic conjugation. Physical characterization of the complexes indicated that the gene complexes were successfully prepared. In vitro, cellular experiments showed excellent biocompatibility of PEI-g-PEG, efficient cellular uptake of the gene complexes, and successful expression of the corresponding fragments. Through gene silencing technique, PEI-g-PEG/PDGFR-α shRNA successfully inhibited the process of EMT in vitro. Furthermore, in vivo animal experiments suggested that this method could effectively inhibit the progression of fibroproliferative membranes of PVR. Herein, a feasible and promising clinical idea was provided for developing non-viral gene vectors and preventing fibroblastic eye diseases by RNA interference (RNAi) technology.
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SENSORS
·
2018
·Vol. 18
·期 9
·2980
·
IF 2.475
Zhizhong Han,Qinghua Weng,Chaofan Lin,Jinquan Yi,Jie Kang
In this work, the CdSe–ZnO flower-rod core-shell structure (CSZFRs) was prepared by ion-exchange method. The surface of CSZFRs was modified by 3-mercaptopropionic acid (MPA), and then the DNA probe was immobilized on the surface via chemical bond between -NH2of DNA probe and -COOH of MPA. Finally, the target norovirous (NV) RNA was combined with the probe according to the principle of complementary base pairing, resulting in a decrease of the photocurrent. The results show that the absorbance spectrum of visible light is enhanced for CSZFRs compared with pure ZnO. Under visible light irradiation, the photocurrent of CSZFRs is up to 0.1 mA, which can improve the sensitivity of the photoelectrochemical (PEC) biosensor. In the measurement range of 0–5.10 nM, the measured concentrations (c) have a good linear relationship with the output photocurrent of the biosensor. The linear regression equation is expressed asI= 0.03256 − 0.0033c(R2= 0.99, S/N = 3) with a detection limit of 0.50 nM. Therefore, this work realizes a rapid and sensitive method for the detection of NV RNA.Keywords:CdSe–ZnO flower-rod;photoelectrochemical biosensor;norovirous RNA;ion-exchange method
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Cardiovascular Therapeutics
·
2022
·
IF 3.368
Sheng Wang,Zhaoyun Cheng,Xianjie Chen,Guoqing Lu,Xiliang Zhu,Gaojun Xu
Objective. Long noncoding RNAs (lncRNAs), including some members of small nucleolar RNA host gene (SNHG), are important regulators in myocardial injury, while the role of SNHG4 in myocardial infarction (MI) is rarely known. This study is aimed at exploring the regulatory role and mechanisms of SNHG4 on MI. Methods. Cellular and rat models of MI were established. The expression of relating genes was measured by qRT-PCR and/or western blot. In vitro, cell viability was detected by MTT assay, and cell apoptosis was assessed by caspase-3 level, Bax/Bcl-2 expression, and/or flow cytometry. The inflammation was evaluated by TNF-α, IL-1β, and IL-6 levels. The myocardial injury in MI rats was evaluated by echocardiography, TTC/HE/MASSON/TUNEL staining, and immunohistochemistry (Ki67). DLR assay was performed to confirm the target relationships. Results. SNHG4 was downregulated in hypoxia-induced H9c2 cells and MI rats, and its overexpression enhanced cell viability and inhibited cell apoptosis and inflammation both in vitro and in vivo. SNHG4 overexpression also decreased infarct and fibrosis areas, relieved pathological changes, and improved heart function in MI rats. In addition, miR-148b-3p was an action target of SNHG4, and its silencing exhibited consistent results with SNHG4 overexpression in vitro. DUSP1 was a target of miR-148b-3p, which inhibited the apoptosis of hypoxia-induced H9c2 cells. Both miR-148b-3p overexpression and DUSP1 silencing weakened the effects of SNHG4 overexpression on protecting H9c2 cells against hypoxia. Conclusions. Overexpression of SNHG4 relieved MI through regulating miR-148b-3p/DUSP1, providing potential therapeutic targets.
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Reproductive Biology
·
2022
·
IF 2.089
Lifang Liu,Bingkai Han,Lixia Liu,Hongying Cui,Hao Liu,Rui Jia,Xiaoyan Zhang,Xiaoxiao Lu
Circular RNAs (circRNAs) have been reported to be implicated in the tumorigenesis and progression of ovarian cancer. Here, the study was designed to explore the activity of human circ_0021573 in ovarian cancer pathogenesis and its regulation through the competing endogenous RNA (ceRNA) crosstalk. Circ_0021573, microRNA (miR)− 936, and cullin 4B (CUL4B) were quantified by qRT-PCR and western blot . Cell proliferation ability was detected by XTT, 5-Ethynyl-2′-Deoxyuridine (EdU), and colony formation assays. Cell apoptosis , migration, and invasion were assessed by flow cytometry, wound-healing, and transwell assays, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-936 and circ_0021573 or CUL4B 3′UTR. Xenograft studies were applied to assess the role of circ_0021573 in tumor growth. Our data showed that circ_0021573 expression is enhanced in human ovarian cancer. Inhibition of circ_0021573 impedes cell proliferation, migration, and invasion and promotes apoptosis in vitro , as well as diminishes tumor growth in vivo . Mechanistically, circ_0021573 contains a miR-936 binding site, and miR-936 is a relevant mediator of circ_0021573 regulation. MiR-936 direct targets and inhibits CUL4B. MiR-936-mediated suppression of CUL4B hinders cell proliferation, migration, and invasion and accelerates apoptosis in vitro. . These data suggested that circ_0021573 might promote the malignant phenotypes of ovarian cancer cells by functioning as a ceRNA for miR-936 to induce CUL4B, which provided a promising target for the prevention and inhibition of ovarian cancer.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Wenbo Wang,Shihao Zhou,Zhaoyi Cheng,Dong Ma,Tao Liu
CRISPR-Cas9 technology has been proven to be the most straightforward and accurate tool for gene therapy, but some limitations, such as the inefficient transfection or inability to precisely target, prevent the gene therapy from achieving the desired therapeutic effect. To overcome these, a kind of glutathione-sensitive cationic vectors, hyperbranched polyamide amine (HPAA) was designed for Delivery of CRISPR-Cas9 RNA plasmid, and the cyclic RGD (Arg-Gly-Asp) was conjugated for the targeted treatment of nasopharyngeal carcinoma (NPC). Disulfide bonds in HPAA segments can specifically respond to the high glutathione concentration in the tumor microenvironment. Meanwhile, RGD could especially interact to the integrin α v β 3 receptors which are highly expressed on the surface of NPC tumor cells. The results showed that more HPAA-RGD/SGK3-gRNA complexes could be uptaken by NPC HNE-1 cells after RGD was conjugated, and then the plasmid could be accumulated in the NPC tumor as well, which may assure the satisfied NPC therapy effect in vivo. In transfection assays, this complex showed the acceptable gene transfection efficiency in vitro and the obvious tumor inhibition effect in vivo, suggested a potential application in gene therapy to NPC.
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ANTI-CANCER DRUGS
·
2021
·Vol. 33
·期 1
·e145
·
IF 2.248
Liu Dan,Wang Yaya,Li Haiming,Peng Sida,Tan Huo,Huang Zhenqian
Multiple myeloma is a frequent hematologic malignancy. Bortezomib is the first-line drug for multiple myeloma chemotherapy. The present study aimed to investigate the potential role and mechanism of circular RNA chaperonin containing TCP1 subunit 3 (circ-CCT3) in bortezomib resistance of multiple myeloma . The levels of circ-CCT3, microRNA-223-3p ( miR-223-3p ), and bromodomain-containing 4 (BRD4) were detected by quantitative real-time PCR or western blot. Cell Counting Kit-8 (CCK-8) method was used to measure the half-inhibitory concentration of bortezomib and cell viability. Cell cycle distribution, apoptosis, proliferation and migration were determined by flow cytometry, 5-ethynyl-2′-deoxyuridine, and wound healing assay. The levels of relevant proteins were checked via western blot. The binding association between miR-223-3p and circ-CCT3/BRD4 was validated via a dual-luciferase reporter assay. Circ-CCT3 and BRD4 were upregulated, while miR-223-3p was downregulated in bortezomib -resistant multiple myeloma patients and cells. Silencing of circ-CCT3 enhanced the sensitivity of bortezomib -resistant multiple myeloma cells to bortezomib . Circ-CCT3 knockdown weakened bortezomib resistance via modulating miR-223-3p . Moreover, miR-223-3p increased bortezomib sensitivity by inhibiting BRD4. Downregulation of circ-CCT3 attenuated bortezomib resistance of multiple myeloma via regulating miR-223-3p /BRD4 pathway, which provided a new potential target for multiple myeloma chemoresistance.
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Aging-US
·
2021
·
IF 5.682
Feng Zhang,Feili Lin,Zhiwen Xu,Zheng Huang
Intervertebral disc degeneration (IDD) is the prevailing spine disorder and is associated with musculoskeletal disease. The extracellular matrix (ECM) degradation is an essential hallmark of IDD progression. Circular RNAs (circRNAs), as crucial cellular regulators, participate in multiple pathological processes including IDD. Here, we tried to explore the effect of circITCH on the ECM degradation of IDD and the underlying mechanism. Significantly, the expression levels of circITCH were elevated in the IDD patients’ nucleus pulposus (NP) tissues relative to that of normal cases. CircITCH promoted apoptosis and decreased proliferation of NP cells. CircITCH contributed to ECM degradation, as demonstrated by increased ADAMTS4 and MMP13 expression and decreased aggrecan and collagen II expression. Mechanically, miR-17-5p could be sponged by circITCH and miR-17-5p inhibited ECM degradation by repressing SOX4 in degenerative NP cells. CircITCH could activate Wnt/β-catenin pathway by targeting miR-17-5p/SOX4 signaling. SOX4 overexpression, miR-17-5p inhibitor, or Wnt/β-catenin signaling activator LiCl was able to reverse circITCH knockdown-inhibited apoptosis and ECM degradation, and circITCH knockdown-enhanced proliferation in NP cells. Thus, we conclude that circITCH promotes ECM degradation in IDD by activating Wnt/β-catenin through miR-17-5p/SOX4 signaling. Our finding presents novel insight into the mechanism that circITCH modulates the IDD progression. CircITCH and SOX4 may serve as potential targets for IDD therapy.
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PLANT CELL
·
2024
·
IF 10
Wu Xinyang,Chen Shuting,Zhang Zixin,Zhou Weixin,Sun Ting,Ning Kang,Xu Min,Ke Xubo,Xu Pei
Virus-induced drought tolerance presents a fascinating facet of biotic-abiotic interaction in plants, yet its molecular intricacies remain unclear. Our study shows that cowpea mild mottle virus (CPMMV) infection enhances drought tolerance in common bean (Phaseolus vulgaris) plants through a virus-derived small interfering RNA (vsiRNA)-activated autophagy pathway. Specifically, a 21-bp vsiRNA originating from the CPMMV Triple Gene Block1 (TGB1) gene targeted the 5' untranslated region (UTR) of the host Teosinte branched 1, Cycloidea, Proliferating Cell Factor (TCP) transcription factor gene PvTCP2, independent of the known role of TGB1 as an RNA silencing suppressor. This targeting attenuated the expression of PvTCP2, which encodes a transcriptional repressor, and in turn upregulated the core autophagy-related gene (ATG) PvATG8c, leading to activated autophagy activity surpassing the level induced by drought or CPMMV infection alone. The downstream EARLY RESPONSIVE TO DEHYDRATION (ERD) effector PvERD15 is a homologue of Arabidopsis thaliana AtERD15, which positively regulates stomatal aperture. PvERD15 was degraded in PvATG8c-mediated autophagy. Therefore, we establish a TGB1-PvTCP2-PvATG8c-PvERD15 module as a trans-kingdom fine-tuning mechanism that contributes to virus-induced drought tolerance in plant-drought-virus interactions.
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ANALYST
·
2017
·Vol. 142
·期 10
·1697-1702
·
IF 3.885
Dianhua Ning,Changtian He,Zhengjie Liu,Cui Liu,Qilong Wu,TingTing Zhao,Renyong Liu
Human telomerase RNA (hTR), which is one component of telomerase, was deemed to be a biomarker to monitor tumor cells due to its different expression levels in tumor cells and normal somatic cells. Thus far, plentiful fluorescent probes have been designed to investigate nucleic acids. However, most of them are limited since they are time-consuming, require professional operators and even result in false positive signals in the cellular environment. Herein, we report a dual-colored ratiometric-fluorescent oligonucleotide probe to achieve the reliable detection of human telomerase RNA in cell extracts. The probe is constructed using a dual-labeled fluorescent oligonucleotide hybridized with target-complemented Dabcyl-labeled oligonucleotide. In the presence of the target, the dual-labeled fluorescent oligonucleotide translates into a hairpin structure, which leads to the generation of the fluorescence resonance energy transfer (FRET) phenomenon under UV excitation. Compared to conventional methods, this strategy could effectively avoid false positive signals, and it not only possesses the advantages of simplicity and high specificity but also has the merits of signal stability and distinguishable color variation. Moreover, the quantitative assay of hTR would have a far-reaching impact on the telomerase mechanism and even tumor diagnosis research.
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