PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2018
·Vol. 115
·期 20
·5175-5180
·
IF 9.504
Peng-Lu Pan,Yu-Xuan Ye,Yi-Han Lou,Jia-Bao Lu,Chen Cheng,Yan Shen,Bernard Moussian,Chuan-Xi Zhang
Cuticle, mainly composed of chitin and cuticular proteins (CPs), is a multifunctional structure of arthropods. CPs usually account for >1% of the total insect proteins. Why does an insect encode so many different CP genes in the genome? In this study, we use comprehensive large-scale technologies to study the full complement of CPs (i.e., the CP-ome) of the brown planthopper (BPH), Nilaparvata lugens, a major rice plant pest. Eight CP families (CPR, CPF, TWDL, CPLCP, CPG, CPAP1, CPAP3, and CPAPn) including 140 proteins in BPH, in which CPAPn is a CP family that we discovered. The CPG family that was considered to be restricted to the Lepidoptera has also been identified in BPH. As reported here, CPLCP family members are characterized by three conserved sequence motifs. In addition, we identified a testis protein family with a peritrophin A domain that we named TPAP. We authenticated the real existence of 106 proteins among the 140 CPs. RNA interference (RNAi) experiments were conducted against 135 CP genes in early- and late-instar nymphs and newly emerged female adults, demonstrating that 32 CPs were essential for BPH normal development or egg production. Combined RNAi experiments suggested redundant and complementary functions of the large number of CPs. Transcriptomic data revealed that the CP genes were expressed in a tissue-specific manner, and there were four clusters of developmental expression patterns. This study gives a comprehensive understanding of the roles of CPs in an insect cuticle.
研究领域:
昆虫学
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基因组学
·
蛋白质组学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2016
·
IF 1.405
De-jing Wang,Chen-meiyi Wang,Yi-ting Wang,Hai Qiao,Liao-qiong Fang,Zhi-biao Wang
Background The complex process by which lactation is initiated upon neonate delivery remains incompletely understood. Microvesicles (MVs) can transmit microRNAs (miRNAs) into recipient cells to influence cell function, and recent studies have identified miRNAs essential for mammary gland development and lactation. This study aimed to investigate the expression of lactation-related miRNAs in MVs isolated from human umbilical cord blood immediately after delivery. Material/Methods Umbilical cord blood samples were collected from 70 healthy pregnant women, and MVs were isolated through differential centrifugation and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were screened using bioinformatics tools for miRNA target prediction, gene ontology, and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression analysis, and the results were validated by real-time PCR. Upon exposure of HBL-100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence confocal microscopy and β-casein secretion was detected by ELISA. Results Spherical MVs extracted from umbilical cord blood expressed CD63 and had an average diameter of 167.0±77.1 nm. We profiled 337 miRNAs in human umbilical cord blood MVs and found that 85 were related to lactation by bioinformatics analysis. The 25 most differentially expressed lactation-related miRNAs were validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture, and significantly increased secretion of β-casein was observed after 96 h from cells exposed to MVs (P<0.05). Conclusions Umbilical cord blood MVs contain many lactation-related miRNAs and can induce β-casein production by HBL-100 cells in vitro . Thus, umbilical cord blood MVs may mediate secretion of β-casein through miRNAs, thereby playing an important role in fetal-maternal crosstalk.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Siting Sheng,Huiling Zhao,Lirui Liu,Dan Chen,Xingdi Wu,Chujun Liu,Xinyu Ma,Jing-Wei Xu,Jian Ji,Haijie Han,Wen Xu
Uveitis, a frequently recurrent inflammatory condition of the uvea, poses a significant risk of visual impairment and blindness, primarily due to the excessive generation of reactive oxygen species (ROS) and the activation of signaling pathways that propagate inflammatory responses. Despite the widespread use of corticosteroid eye drops as a standard treatment, these therapies are hindered by limited efficacy, adverse side effects, and poor ocular bioavailability. To address these challenges, polyethyleneimine (PEI)-modified polydopamine (PDA) carrying microRNA-132-3p (miR-132), namely PEI/PDA@miR-132, was developed to simultaneously neutralize ROS and attenuate inflammation in experimental models of acute and chronic uveitis. Mechanistically, PEI/PDA@miR-132 demonstrated remarkable efficacy by suppressing ROS production, inhibiting the pro-inflammatory polarization of macrophages, and downregulating the I κ B α /nuclear factor-kappa B (NF- κ B) p65 signaling pathway. These effects culminated in the reduction of pro-inflammatory cytokines and mitigation of apoptosis. Therapeutically, PEI/PDA@miR-132 provided significant relief from hallmark symptoms of uveitis, including iris congestion, inflammatory exudation, and retinal folds, while exhibiting superior retinal safety compared to commercially available dexamethasone. Furthermore, it showcased excellent biocompatibility, positioning it as a promising therapeutic strategy for managing oxidative stress- and inflammation-driven diseases such as acute and chronic uveitis.
研究领域:
药理学
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眼科
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纳米医学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-15
·
IF 15.7
Liu Wenjia,Liu Yuting,Zhang Liqiang,Li Liya,Yang Wenguang,Li Jia,He Wangxiao
Liver sinusoidal endothelial cells (LSECs) lose their characteristic fenestrations and become capillarized during the progression of liver fibrosis. Mesenchymal stem cell (MSC) transplantation can reverse this capillarization and reduce fibrosis, but MSC therapy has practical limitations that hinder its clinical use. Here, with the help of artificial intelligence (AI), we show that MSCs secrete a microRNA (miR-325-3p) that helps restore LSEC fenestrations (tiny pores) by modulating their cytoskeleton, effectively reversing capillarization. We further develop a spherical nucleic acid (SNA) nanoparticle carrying miR-325-3p as an alternative to MSC therapy. This SNA specifically enters fibrotic LSECs via the scavenger receptor A (Scara). In three mouse models of liver fibrosis, the SNA treatment restores LSEC fenestrations, reverses capillarization, and significantly reduces fibrosis without adverse effects. Our findings highlight the potential of SNA-based therapy for liver fibrosis, paving the way for targeted nucleic acid treatments directed at LSECs and offering hope for patients.
研究领域:
分子生物学
·
肝脏病学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 8
·1-7
·
IF 5.479
Li Mei,Xu Xiong,Cai QingYou,Luo XuJian,Zhou ZhongGao,Xu GuoHai,Xie YongRong
A graphene oxide-based method has been developed for ultrasensitive and selective determination of microRNA-141 by means of rolling circle amplification (RCA) and exonuclease III (Exo III)-assisted recycling amplification. The method uses (a) a padlock probe with a hybrid sequence that is complementary to the target microRNA-141 at both the 5'- and the 3'-end, and (b) a long binding region of a signalling reporter strand. On addition of microRNA-141, it acts as the primer for triggering the RCA reaction following ligation. This results in the formation of a repeatedly concatenated sequence of the padlock probe. Subsequently, the RCA product hybridizes with the fluorescein-labelled signal strand to form the duplex DNA containing the blunt 3'-termini of signal strand. Addition of Exo III causes signal strand digestion and leads to RCA product recycling and liberation of fluorescein. Added graphene oxide does not absorb the fluorescein liberated because of the poor mutual interaction. Therefore, microRNA-141 can be quantified by measurement of the green fluorescence under excitation/emission wavelengths of 470/520 nm. The method has a 100 aM detection limit towards microRNA-141 and works in the wide range from 1 fM to 1 nM. It can discriminate even single-mismatched microRNA and shows good selectivity and sensitivity when applied to spiked human serum.
Schematic representation of a graphene oxide (GO)-based method for fluorometric determination of microRNA by using rolling circle amplification and exonuclease III (Exo III)-aided recycling amplification. With microRNA, the fluorescein-labelled signal strand becomes digested, and this genererates a fluorescent signal.
研究领域:
分子生物学
·
生物化学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Insects
·
2021
·Vol. 12
·期 4
·370
·
IF 2.769
Zuo-min Shao,Jian-hao Ding,De-lei Jiang,Zhi-xiang Liu,Yi-jiangcheng Li,Jiao Wang,Jun Wang,Sheng Sheng,Fu-an Wu
Simple SummarySericulture has always been threatened byGlyphodes pyloalisWalker (G. pyloalis). Trehalase is an essential enzyme in chitin metabolism and energy supply. In this study, two trehalase genes inG. pyloalis(GpTre1andGpTre2) were identified and functionally analyzed. Knockdown of the two genes led to the significant downregulation of chitin metabolism pathway-related genes, the difficulty in molting of larvae, and the deformation of adult wings. Moreover, the trehalase inhibitor, Validamycin A, treatment increasedGpTre1andGpTre2expression and affected the expressions of chitin metabolism pathway-related genes. The inhibitor also caused a significantly increased cumulative mortality of larvae. The results suggested thatGpTre1andGpTre2played a vital role onG. pyloalisdevelopment, which could be useful for providing information for insect pest control in the future.AbstractGlyphodes pyloalisWalker (G. pyloalis) is a serious pest on mulberry. Due to the increasing pesticide resistance, the development of new and effective environmental methods to controlG. pyloalisis needed. Trehalase is an essential enzyme in trehalose hydrolysis and energy supply, and it has been considered a promising target for insect pest control. However, the specific function oftrehalaseinG. pyloalishas not been reported. In this study, two trehalase genes (GpTre1andGpTre2) were identified from our previous transcriptome database. The functions of thetrehalasein chitin metabolism were studied by injecting larvae with dsRNAs and trehalase inhibitor, Validamycin A. The open reading frames (ORFs) of GpTre1 and GpTre2 were 1,704 bp and 1,869 bp, which encoded 567 and 622 amino acid residues, respectively. Both ofGpTre1andGpTre2were mainly expressed in the head and midgut. The highest expression levels of them were in 5th instar during different development stages. Moreover, knockdown both ofGpTre1andGpTre2by the dsRNAs led to significantly decreased expression of chitin metabolism pathway-related genes, includingGpCHSA,GpCDA1,GpCDA2,GpCHT3a,GpCHT7,GpCHSB,GpCHT-h,GpCHT3b,GpPAGM,andGpUAP, and abnormal phenotypes. Furthermore, the trehalase inhibitor, Validamycin A, treatment increased the expressions ofGpTre1andGpTre2, increased content of trehalose, and decreased the levels of glycogen and glucose. Additionally, the inhibitor caused a significantly increased cumulative mortality ofG. pyloalislarvae on the 2nd (16%) to 6th (41.3%) day, and decreased the rate of cumulative pupation (72.3%) compared with the control group (95.6%). After the activities of trehalase were suppressed, the expressions of 6 integument chitin metabolism-related genes decreased significantly at 24 h and increased at 48 h. The expressions ofGpCHSBandGpCHT-h, involved in chitin metabolism pathway of peritrophic membrane in the midgut, increased at 24 h and 48 h, and there were no changes toGpCHT3bandGpPAGM. These results reveal thatGpTre1andGpTre2play an essential role in the growth ofG. pyloalisby affecting chitin metabolism, and this provides useful information for insect pest control in the future.Keywords:Glyphodes pyloalisWalker;trehalase;chitin metabolism;Validamycin A;RNA interference;pest control
研究领域:
昆虫学
·
分子生物学
·
害虫防治
✓ 已验证
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2021
·Vol. 45
·期 8
·1710-1719
·
IF 3.612
Yulan Gu,Chuandan Wan,Guoqiang Zhou,Jinlian Zhu,Zhiliang Shi,Zhixiang Zhuang
Gastric cancer (GC) is a kind of malignancy originating from the epithelium of gastric mucosa. Long noncoding RNAs (lncRNAs) are tightly related to the GC progression. Herein, our research was meant to investigate a novel lncRNA thymidylate synthetase opposite strand ( TYMSOS ) in GC. Quantitative real-time polymerase chain reaction was used to analyze TYMSOS expression in GC cells. 5-Ethynyl-2ʹ-deoxyuridine, flow cytometry analysis, and transwell assay detected the influence of TYMSOS on GC cell proliferation, apoptosis, migration, and invasion. Subcellular fractionation and fluorescent in situ hybridization assays determined the cellular localization of TYMSOS in GC cells. Bioinformatics programs, RNA-binding protein immunoprecipitation, RNA pull-down, and luciferase reporter assays measured the molecular interplays of TYMSOS in GC cells. In brief, TYMSOS was highly expressed in GC cells, and TYMSOS silence inhibited GC cell proliferation, migration, and invasion while elevating cell apoptosis. Functionally, TYMSOS functioned as a competing endogenous RNA to posttranscriptionally modulate GC progression. TYMSOS interacted with miR-4739 to regulate its target gene zinc finger protein 703 . Collectively, our study proved the tumor-promoting role of TYMSOS in GC cells, which might offer the utility value for GC treatment.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2014
·
IF 5.825
Yi Zhang,Lu Zhang,Jiashu Sun,Yulei Liu,Xingjie Ma,Shangjin Cui,Liying Ma,Jianzhong Jeff Xi,Xingyu Jiang
This report demonstrates a straightforward, robust, multiplexed and point-of-care microcapillary-based loop-mediated isothermal amplification (cLAMP) for assaying nucleic acids. This assay integrates capillaries (glass or plastic) to introduce and house sample/reagents, segments of water droplets to prevent contamination, pocket warmers to provide heat, and a hand-held flashlight for a visual readout of the fluorescent signal. The cLAMP system allows the simultaneous detection of two RNA targets of human immunodeficiency virus (HIV) from multiple plasma samples, and achieves a high sensitivity of two copies of standard plasmid. As few nucleic acid detection methods can be wholly independent of external power supply and equipment, our cLAMP holds great promise for point-of-care applications in resource-poor settings.
研究领域:
分子生物学
·
医学诊断
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
YONSEI MEDICAL JOURNAL
·
2021
·
IF 2.759
Chunting Hu,Chen Li,Qiaoya Ma,Ruili Wang,Ya He,Hui Wang,Guogang Luo
Purpose Ischemic brain injury results in high mortality and serious neurologic morbidity. Here, we explored the role of SNHG15 in modulating neuronal damage and microglial inflammation after ischemia stroke. Materials and Methods The hypoxia/ischemia models were induced by middle cerebral artery occlusion in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to determine the levels of SNHG15, miR-302a-3p, and STAT1/NF-κB. Moreover, gain- or loss-of functional assays of SNHG15 and miR-302a-3p were conducted. MTT assay was used to evaluate the viability of HT22 cells, and the apoptotic level was determined by flow cytometry. Furthermore, enzyme-linked immunosorbent assay was performed to detect oxidative stress and inflammatory mediators in the ischemia cortex and OGD/R-treated BV2 microglia. Results The SNHG15 and STAT1/NF-κB pathways were both distinctly up-regulated, while miR-302a-3p was notably down-regulated in the ischemia cortex. Additionally, overexpressing SNHG15 dramatically enhanced OGD/R-mediated neuronal apoptosis as well as the expression of oxidative stress and inflammation factors from microglia. In contrast, knocking down SNHG15 or overexpressing miR-302a-3p relieved OGD/R-mediated neuronal apoptosis and microglial activation. Moreover, the rescue experiment testified that overexpressing miR-302a-3p also attenuated SNHG15 up-regulation-induced effects. In terms of the mechanisms, SNHG15 sponged miR-302a-3p and activated STAT1/NF-κB as a competitive endogenous RNA, while miR-302a-3p targeted STAT1 and negatively regulated the STAT1/NF-κB pathway. Conclusion SNHG15 was up-regulated in the hypoxia/ischemia mouse or cell model. The inhibition of SNHG15 ameliorates ischemia/hypoxia-induced neuronal damage and microglial inflammation by regulating the miR-302a-3p/STAT1/NF-κB pathway.
研究领域:
神经科学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-11
·
IF 4.996
Wan Yiting,Gu Cancan,Kong Jueying,Sui Jin,Zuo Ling,Song Yanhua,Chen Jing
Endometriosis (EMs) is one of the most frequent diseases of reproductive-age women and is characterized by the growth of endometrial tissues beyond the uterus. The enhanced proliferative and migratory potential of endometrial stromal cells (ESCs) plays an important role in the progression of EMs. Mounting studies have demonstrated that long noncoding RNAs (lncRNAs) exert an important role in regulating the development and progression of EMs. Given the aberrant expression of lncRNA ADAMTS9-AS1 in ectopic endometrium (ecEM), we investigated the biological effect of ADAMTS9-AS1 on ESC proliferation and migration and explored the underlying mechanism. The current data showed that ADAMTS9-AS1 expression was significantly upregulated in ecEM compared with eutopic endometrium (euEM) in patients with EMs and in a murine model of EMs. Functionally, ADAMTS9-AS1 knockdown in ectopic ESCs (EESCs) decreased cell viability and migration, whereas ADAMTS9-AS1 overexpression in normal ESCs (NESCs) enhanced cell viability and migration. More importantly, the effect of ADAMTS9-AS1 inhibition on decreasing ESC viability was significantly blocked by ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and ADAMTS9-AS1 overexpression repressed erastin (a ferroptosis activator)-induced cell death. Furthermore, the regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) levels and malonyl dialdehyde (MDA) content and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of EMs.
研究领域:
妇科学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2019
·Vol. 38
·期 1
·1-12
·
IF 5.646
Shi Weidong,Zhang Chenyue,Ning Zhouyu,Hua Yongqiang,Li Ye,Chen Lianyu,Liu Luming,Chen Zhen,Meng Zhiqiang
Background Long non-coding RNA LINC00346 has been recently suggested as a prognostic marker in pancreatic cancer. However, its biological function in pancreatic cancer has not yet been determined. In this study, we attempted to ascertain the role of LINC00346 in regulating the aggressiveness of pancreatic cancer.Methods The effects of overexpression and knockdown of LINC00346 on the proliferation, cell cycle progression, apoptosis, and gemcitabine resistance were investigated. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation assay were performed to search for potential microRNAs (miRs) that can interact with LINC00346.Results Overexpression of LINC00346 significantly enhanced the proliferation, colony formation, and tumorigenesis of pancreatic cancer cells. Conversely, knockdown of LINC00346 suppressed pancreatic cancer cell proliferation and caused a cell-cycle arrest at the G2/M-phase. Depletion of LINC00346 also enhanced gemcitabine sensitivity in pancreatic cancer cells both in vitro and in vivo. Mechanistic investigation revealed that LINC00346 acted as a sponge for miR-188-3p and blocked the repression of BRD4 by miR-188-3p in pancreatic cancer cells. Clinical evidence indicated a negative correlation between LINC00346 and miR-188-3p in pancreatic cancer specimens. Rescue experiments showed that LINC00346 attenuated the growth-suppressing and chemosensitizing effects of miR-188-3p on pancreatic cancer cells. In addition, silencing of BRD4 significantly inhibited LINC00346-induced pancreatic cancer cell proliferation and colony formation.Conclusion sLINC00346 shows the ability to promote pancreatic cancer growth and gemcitabine resistance, which is in part mediated by antagonization of miR-188-3p and induction of BRD4. Targeting LINC00346 may improve gemcitabine-based therapeutic efficacy.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
✓ 已验证
DOI
PubMed
高影响因子
Molecular BioSystems
·
2017
·Vol. 13
·期 10
·2125-2134
·
IF 2.781
Qianqian Wang,Fei Lu,Rongfeng Lan
Overcoming chemoresistance will prevent cancer relapse and contribute to clinical chemotherapy. In order to explore the underlying mechanism of chemoresistance, we firstly incubated cancer cells with a combination of cisplatin + paclitaxel (C + P) or cisplatin + paclitaxel + docetaxel (C + P + D) to mimic the treatment of cancer therapy in the laboratory. We found that polyploidy is a recurring strategy that cells adopt in response to cisplatin-based treatments. RNA-sequencing was performed to identify differentially expressed genes (DEGs) that may contribute to drug resistance. 4830 and 5518 DEGs were discovered in C + P and C + P + D resistant cells, respectively, and 4384 (73.40%) genes were shared. Possible drug resistance genes like Atg14, Abcb1b, Tbx2, Slc2a9, Slc10a3 and Slc22a18 were up-regulated while Foxm1, Bcl2, Brca1, Chek1, Hiatl1 and Abcb9 were down regulated. Genes involved in the pathways of p53 signaling, lysosomes and apoptosis were up-regulated, and in contrast, genes in the cell cycle, DNA replication, and mismatch repair pathways were down-regulated. Moreover, representative proteins relative to DEGs were examined to validate the results of RNA-seq and RT-PCR. Taken together, these results will contribute to revealing the mechanism of chemoresistance and discovering potential prognostic factors for cancer medication.
研究领域:
肿瘤学
·
分子生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）