Small
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2023
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IF 13.3
Huimin Xu,Jianqiao Chang,Hao Wu,Haoyu Wang,Wenjing Xie,Yunchao Li,Xiaohong Li,Yang Zhang,Louzhen Fan
Small interfering RNA (siRNA)-based gene therapy represents a promising strategy for tumor treatment. Novel gene vectors that can achieve targeted delivery of siRNA to the tumor cells without causing any side effects are urgently needed. To this end, the large amino acid mimicking carbon dots with guanidinium functionalization (LAAM GUA-CDs) are designed and synthesized by choosing arginine and dopamine hydrochloride as precursors. LAAM GUA-CDs can load siRNA through the multiple hydrogen bonds between their guanidinium groups and phosphate groups in siRNA. Meanwhile, the amino acid groups at the edges of LAAM GUA-CDs endow them the capacity to target tumors. After loading siBcl-2 as a therapeutic agent, LAAM GUA-CDs/siBcl-2 has a high tumor inhibition rate of up to 68%, which is twice more than that of commercial Lipofectamine 2000. Furthermore, LAAM GUA-CDs do not cause side effect during antitumor treatment owing to their high tumor-targeting ability, thus providing a versatile strategy for tumor-targeted siRNA delivery and cancer therapy.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2023
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IF 5.1
Hongzhou Lin,Huihui Chen,Rengcheng Qian,Guoqi Tang,Yinjuan Ding,Yalan Jiang,Congde Chen,Dexuan Wang,Maoping Chu,Xiaoling Guo
Background Nephrotic syndrome (NS) is a chronic kidney disease mainly caused by impaired podocytes, ultimately resulting in massive proteinuria or even end-stage renal disease (ESRD). Methods The objective of this study was to explore the potential pathogenesis of NS caused by podocyte injury, and further explore the underlying mechanism through data mining , bioinformatics analysis, and experimental verification. The integrated analyses including Seurat, CellChat, gene ontology (GO), and molecular docking were performed based on the single-cell RNA-seq data (scRNA-seq). The adriamycin (ADR)-induced podocyte injury model in vitro was established to conduct the experimental verification for bioinformatics analysis results through western blot and real-time quantitative PCR (RT-qPCR). Results The results of bioinformatics analysis revealed that the bone morphogenetic protein (BMP) signaling pathway was involved in the podocyte-to-podocyte communication, which plays a crucial role in podocyte injury. The expression of BMP7 was significantly increased in ADR-induced podocytes through activating the Adenosine-monophosphate activated-protein kinase/Mammalian target of rapamycin (AMPK/mTOR) mediated autophagy pathway, and these findings were confirmed by in vitro experiments. Conclusion This study first demonstrated that BMP7 participated in ADR-induced podocyte injury. The BMP7/AMPK/mTOR mediated autophagy pathway may play a crucial role in podocyte injury, which may be the potential therapeutic target for NS patients.
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Frontiers in Cell and Developmental Biology
·
2022
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IF 6.081
Zhou Tong,Chen Guobin,Chen Meng,Wang Yubin,Zou Guiwei,Liang Hongwei
Sex dimorphism is a key feature of Chinese soft-shelled turtle (Pelodiscus sinensis). The males (M) have higher econosmic value than females (F) due to wider calipash and faster growth. Exogenous hormones like estradiol and methyltestosterone can induce sexual reversal to form new phenotypes (pseudo-female, PF; pseudo-male, PM) without changing the genotype. The possibility of inducing sexual reversal is particularly important in aquaculture breeding, but the underlying biological mechanisms remain unclear. Here we applied a direct RNA sequencing method with ultralong reads using Oxford Nanopore Technologies to study the transcriptome complexity in P. sinensis. Nanopore sequencing of the four gender types (M, F, PF, and PM) showed that the distribution of read length and gene expression was more similar between same-sex phenotypes than same-sex genotypes. Compared to turtles with an M phenotype, alternative splicing was more pronounced in F turtles, especially at alternative 3′ splice sites, alternative 5′ splice sites, and alternative first exons. Furthermore, the two RNA methylation modifications m5C and m6A were differentially distributed across gender phenotypes, with the M type having more modification sites in coding sequence regions, but fewer modification sites in 3′UTR regions. Quantitative analysis of enriched m6A RNAs revealed that the N6-methylated levels of Odf2, Pacs2, and Ak1 were significantly higher in M phenotype individuals, while the N6-methylated levels of Ube2o were reduced after sexual reversal from both M and F phenotypes. Taken together, these findings reveal an important role of epigenetics during sexual reversal in Chinese soft-shelled turtles.
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TISSUE & CELL
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2022
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IF 2.586
Xiaoping Wu,Qiujie Pang,Fuxiang Zhi,Xiaohong Mao,Yingbin Hu
The role of long non-coding RNA ACTA2 antisense RNA 1 (LncRNA ACTA2-AS1) in colorectal cancer (CRC) was awaited to be elucidated. Clinical specimen and data on ACTA2-AS1 expression in colon adenocarcinoma (COAD) were collected, followed by in situ hybridization . Transfected CRC cell viability, proliferation, migration, and invasion were determined with Cell Counting Kit-8, colony formation, Scratch, and Transwell assays, respectively. Relative expressions of ACTA2-AS1, PCNA, Bcl-2, MMP-2 and MMP-9 were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot . ACTA2-AS1 expression was downregulated in CRC. Overexpressed ACTA2-AS1 repressed the cell viability, proliferation, migration and invasion, increased cleaved caspase-3 level yet decreased PCNA, Bcl-2, MMP-2 and MMP-9 levels. ACTA2-AS1 silencing, however, did oppositely. Collectively, ACTA2-AS1 inhibits the viability, proliferation, migration and invasion of CRC cells to effectively suppress the progression of CRC.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2023
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IF 8.4
Xueliang Lin,Youliang Weng,Yi Liu,Duo Lin,Huishan Yang,Zhiwei Chen,Shangyuan Feng
The rapid and high precision analysis of SARS-CoV-2 RNA in saliva is crucial for the efficient prevention and control of COVID-19. Herein, we developed a novel ratiometric surface-enhanced Raman spectroscopy (SERS) sensing chip based on a two-dimensional core-molecule-shell-molecule nanostructure for quantitative detection of SARS-CoV-2 RNA. Owing to the use of base-complementary pairing mechanism, this SERS sensing chip has better selectivity in discriminating SARS-CoV-2 RNA against other RNA. Besides, an internal standard molecule (4MBN) in the SERS sensing chip can used to calibrate the real-time changing Raman signals of the probe molecule during quantitative assay. Using this cleverly designed SERS sensing chip, the dynamic ranges from 10 –6 M to 10 –12 M with a low of detection limit (LOD = 7.61 ×10 –14 M) can be acquired for detection of SARS-CoV-2 RNA. Meanwhile, this SERS sensing chip was well adapted for point-of-care testing (POCT) in combination with portable Raman spectrometer, which is expected to achieve effective detection of early SARS-CoV-2 infection.
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BMC Pulmonary Medicine
·
2021
·Vol. 21
·期 1
·1-12
·
IF 3.317
Kang Honggang,Ma Dan,Zhang Jing,Zhao Jun,Yang Mengxiang
Background Lung adenocarcinoma (LUAD) is known to be one of the leading causes of cancer-related deaths globally. In recent decades, long non-coding RNAs (lncRNAs) have been indicated to exert pivotal regulating functions in multiple biological behaviors in the initiation and development of LUAD. However, the functional mechanism of lncRNA GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in LUAD has not been explored. Methods In the current study, GATA6-AS1 expression in LUAD tissues was revealed. Meanwhile, GATA6-AS1 expression in LUAD cells was investigated via RT-qPCR analysis. After A549 and H1975 cells were transfected with GATA6-AS1 overexpression plasmids, EdU and colony formation assays, TUNEL assays and flow cytometry analyses, as well as wound healing and Transwell assays were conducted to detect cell proliferation, apoptosis, migration and invasion. Afterwards, bioinformatic tools, western blot analyses, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays were performed to investigate the correlation of microRNA-4530 (miR-4530), GATA6-AS1 and GATA6. Results We found that GATA6-AS1 expression was low-expressed in LUAD tissues and cells. Furthermore, the upregulation of GATA6-AS1 suppressed the proliferative, migration and invasion abilities, as well as promoted apoptotic rate of A549 and H1975 cells. Moreover, the mechanistic investigations revealed that GATA6-AS1 upregulated the expression of its cognate sense gene GATA6 by binding with miR-4530, thereby modulating the malignant progression of LUAD cells. Conclusions GATA6-AS1 repressed LUAD cell proliferation, migration and invasion, and promoted cell apoptosis via regulation of the miR-4530/GATA6 axis, indicating GATA6-AS1 as a new prognostic biomarker for LUAD.
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MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2020
·Vol. 475
·期 1
·1-13
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IF 2.795
Lin Lin,Xin Bing,Jiang Tao,Wang Xin-lu,Yang Hua,Shi Tie-mei
Long non-coding RNAs are associated with the pathogenesis of cancers. Moreover, LINC00460 is involved in the development of multiple cancers. However, the function of LINC00460 in cervical cancer (CC) remains inconclusive. Herein, CC tissues and tumor-adjacent tissues were collected from patients. The effect of LINC00460 silencing in cell proliferation and apoptosis in CC was explored in vitro and in vivo. Additionally, the interaction between LINC00460 and miR-503-5p was analyzed using dual luciferase reporter assay. The expression of genes and proteins was assayed using quantitative real-time PCR, western blotting and immunohistochemistry, cell viability using MTT assay, cell cycle distribution using flow cytometry, cell apoptosis using Annexin V staining, Hoechst staining and TUNEL assay. LINC00460 levels in CC tissues were higher than tumor-adjacent tissues. LINC00460 silencing suppressed proliferation and promoted apoptosis of CC cells as evidenced by decreased cell viability, inhibited proliferation-related protein and cell cycle protein expressions and G1/S transition, increased apoptotic cells and Hoechst-positive cells, and enhanced apoptosis-related protein expressions. LINC00460 could bind to miR-503-5p and LINC00460 silencing enhanced miR-503-5p expression and inhibited its target gene expressions in CC cells. MiR-503-5p inhibition reversed LINC00460 silencing-caused inhibition of cell proliferation and miR-503-5p target gene expressions, and promotion of cell apoptosis. LINC00460 silencing also attenuated tumor growth, promoted miR-503-5p levels and cell apoptosis, and inhibited cell proliferation and miR-503-5p target gene expressions in tumor tissues. Hence, LINC00460 functioned as an oncogene in CC that affected cell proliferation and apoptosis via sponging miR-503-5p. This study provides a novel therapeutic target for CC.
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ELECTROCHIMICA ACTA
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2020
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IF 6.215
Qingqing Zhang,Tingting Hao,Dandan Hu,Zhiyong Guo,Sui Wang,Yufang Hu
A new RNA aptamer-involved electrochemiluminescence (ECL) strategy for sensitive detection of histone acetyltransferase (HAT p300) is designed well based on coenzyme A (CoA)-initiated competitive response and advanced DNA nano-biotechnology. For the first time, this interesting analytical process is comprised of significant histone acetylation catalyzed by HAT p300, competitive replacement triggered by the specific binding of CoA and its RNA aptamer , stable scaffold guided by DNA nano-prism and typical amplification managed by hybrid chain reaction (HCR). Upon recognition of the RNA aptamer to CoA generated in acetylation, auxiliary DNA (A-DNA) which can be captured by three hanging arms of the fabricated DNA nano-prism immobilized onto Au electrode surface is released from the aptamer/A-DNA complex. Moreover, A-DNA can also open skillfully one hairpin DNA (H1), then turning into HCR process by alternating hybridization with the other hairpin DNA (H2). Abundant Ru(phen) 3 2+ molecules which have a strong interaction with dsDNA can result in a significant output. This proposed platform exhibits excellent specificity and sensitivity toward HAT p300 with a detection limit of 0.001 nM and takes on outstanding practicality and superiority, which presents a great potential for HAT p300 analysis in biomedical sciences.
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Experimental and Therapeutic Medicine
·
2020
·Vol. 20
·期 6
·1-1
·
IF 1.785
Tongtong Niu,Yan An,Tingting Lv,Dongning Liu
Diabetic retinopathy (DR) is a serious complication of diabetes and the most common metabolic disorder. Recently, long non‑coding (lnc)RNAs have been identified as critical regulators of DR. Ribosomal protein SA pseudogene 52 (RPSAP52) is an oncogenic lncRNA expressed in pituitary tumors. The present study aimed to investigate the functions of RPSAP52 in DR. RPSAP52 levels in the plasma of diabetic patients with or without DR complication was detected. Luciferase reporter assays, RT‑qPCR and western blotting were performed to detect the interaction between RPSAP52 and micro RNA (miR)‑365. Moreover, expression vectors of RPSAP52 and Timp3, as well as miR‑365 mimics were transfected into ARPE‑19 cells exposed to high glucose and the apoptotic cells were detected. The results showed that RPSAP52 was downregulated in patients with DR compared with patients with diabetes without obvious complications. RPSAP52 directly interacted with miR‑365, while overexpression of RPSAP52 and miR‑365 did not affect the expression of one another. In addition, overexpression of RPSAP52 upregulated TIMP metallopeptidase inhibitor 3 (Timp3) in retinal pigment epithelial (RPE) cells. High glucose treatment led to downregulated RPSAP52 and Timp3, but upregulated miR‑365 in RPE cells. Moreover, cell apoptosis analysis identified that overexpression of RPSAP52 and Timp3 led to a decreased apoptotic rate of RPE cells under high glucose treatment. Therefore, it was speculated that RPSAP52 may upregulate Timp3 by serving as the endogenous sponge of miR‑365 in DR to suppress RPE cell apoptosis.
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Frontiers in Microbiology
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2020
·
IF 4.236
Hu Ao,Li Jing,Tang Wei,Liu Ge,Zhang Haiwei,Liu Chunlan,Chen Xulin
Influenza virus RNA-dependent RNA polymerase (vRdRp) does not have capping activity and relies on the capped RNAs produced by the host RNA polymerase II (RNAPII). The viral polymerases process the capped RNAs to produce short capped RNA fragments that are used as primers to initiate the transcription of viral mRNAs. This process, known as cap-snatching, can be targeted by antiviral therapeutics. Here, anthralin was identified as an inhibitor against influenza a virus (IAV) infection by targeting the cap-snatching activity of the viral polymerase. Anthralin, an FDA-approved drug used in the treatment of psoriasis, shows antiviral activity against IAV infection in vitro and in vivo. Importantly, anthralin significantly reduces weight loss, lung injury, and mortality caused by IAV infection in mice. The mechanism of action study revealed that anthralin inhibits the cap-binding function of PB2 subunit and endonuclease activity of PA. As a result, viral mRNA transcription is blocked, leading to the decreases in viral RNA replication and viral protein expression. In conclusion, anthralin has been demonstrated to have the potential of an alternative antiviral against influenza virus infection. Also, targeting the captive pocket structure that includes the N-terminus of PA endonuclease domain and the C-terminal of PB2 cap-binding domain of IAV RdRp may be an excellent strategy for developing anti-influenza drugs.
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FISH & SHELLFISH IMMUNOLOGY
·
2019
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IF 3.298
Yafei Duan,Yun Wang,Dalin Xiong,Jiasong Zhang
The intestine is important for nutrition, metabolism and immunity. Succinate (SA) plays a vital role in the physiological homeostasis of animal intestines. However, the effects of dietary SA on the intestinal immunity and metabolism in shrimp are not clear. In this study, we investigated the immune and metabolic responses in the intestine of Litopenaeus vannamei that were fed diets consisting of different levels of SA: 0 g/kg (Con) and 10 g/kg (SA) for 56 days. The results from a RNA-seq analysis identified 6005 differentially expressed genes (DEGs), including 2728 upregulated genes and 3277 downregulated genes, which were grouped into 312 pathways. The DEGs were most enriched in pathways related to protein synthesis and amino acid metabolism , including “ribosome”, “aminoacyl-tRNA biosynthesis”, “pyrimidine metabolism”, and “arginine and proline metabolism”; additionally, carbohydrate and lipid metabolism pathways were also activated. A large number of immune-related genes were associated with mucus barrier modification, antimicrobial activity , pathogen attachment and recognition, antioxidant activity , and apoptosis. The expression patterns of several candidate genes involved in the immune response and nutrition metabolism were detected by qPCR. This study provides insight into the transcriptomic modulating mechanisms associated with intestinal immunity and the metabolism of L. vannamei in response to the intake of dietary SA.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Cuiyuan Jin,Caiyun Wang,Chen Zhang,Qi Ye,Yuanxiang Jin,Liyun Shi
As a fungicide with the characteristics of high effectiveness, internal absorption and broad spectrum, imazalil is widely used to prevent and treat in fruits and vegetables. Here, pregnant C57BL/6 mice were exposed to imazalil at dietary levels of 0, 0.025‰, and 0.25‰ through drinking water during pregnancy and lactation. We then analyzed the phenotype, metabolome, and expression of related genes and proteins in the livers of mice. There was a marked decrease in the body and liver weights of male offspring mice after maternal imazalil exposure, while this effect on the dam and female offspring was slight. Metabolomics analyses revealed that imazalil significantly altered the metabolite composition of liver samples from both dams and offspring. The preliminary results of the analysis indicated that glucolipid metabolism was the pathway most significantly affected by imazalil. We performed a coabundance association analysis of metabolites with significant changes in the pathway of glycolipid metabolism, and IMZ altered the networks of both dams and offspring compared with the network in control mice, especially in male offspring. The hepatic triglyceride, non-esterified fatty acid and glucose levels were increased significantly in the dams but decreased significantly in male offspring after maternal imazalil exposure. Furthermore, the expression levels of genes associated with glycolipid metabolism and m 6 A RNA methylation were significantly affected by maternal intake of imazalil. Imazalil-induced glucolipid metabolism disturbance was highly correlated with m 6 A RNA methylation. In conclusion, maternal imazalil exposure resulted in glucolipid metabolism disturbance and abnormal m 6 A RNA methylation in the livers of dams and offspring mice. We expected that the information acquired in this study will provide novel evidence for understanding the effect of maternal imazalil exposure on potential health risks.
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