INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Haijun Wang,Bao Jing,Xinyu Dong,Muning Wang,Yan Xuan,Siyao Chang,Yuxin Qin,Bojian Zhang,Weizhong Zhou,Sheng Wang,Yufeng Lin,Zhiyang Han
Vascular smooth muscle cells (VSMCs) are essential for maintaining vascular tone and participate in all stages of atherosclerosis. The transition of VSMCs into macrophage-like cells is a major source of plaque foam cells. Nevertheless, the mechanisms regulating this phenotypic transition remain elusive. RNA Binding Motif Protein 47 (RBM47) expression was increased by more than twofold in aortas of ApoE − / − mice and was markedly elevated in RBM47 + α-SMA + double-positive cells within atherosclerotic plaques. RBM47 knockdown significantly reduced plaque burden and vascular inflammation, and suppressed VSMC-to-macrophage-like transition. In POV-PC-treated VSMCs, RBM47 knockdown inhibited VSMC proliferation, migration, inflammation, and macrophage-like transition. Mechanistically, RBM47 was found to directly bind to two specific sequences within the 3′UTR of GALNT4 mRNA and enhance its stability. Functional rescue experiments confirmed that GALNT4 mediated the effects of RBM47 on VSMC-to-macrophage-like transition. These findings suggest that RBM47 contributes to atherosclerosis by stabilizing GALNT4 mRNA and promoting VSMC-to-macrophage-like transition.
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高影响因子
Science Advances
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2026
·Vol. 12
·期 13
·
IF 13.9
Taisong Fang,Songbai Liu
Efficient oral delivery of RNA to the target site is a long-standing issue for nucleic acid–based therapy. Herein, we adopted a vesicle-to-vesicle transfer strategy and established an efficient approach to encapsulate and stabilize RNA for targeted oral delivery. The amphiphilic specifically acylated epigallocatechin directly performed encapsulation of RNA and generated nanovesicles in high efficiency without assistance of additional materials. The RNA encapsulated in the nanovesicles was efficiently transferred to outer membrane vesicles (OMVs) derived from Escherichia coli Nissle 1917 probiotic through membrane fusion with simple operation. The derived hybrid vesicles (HVs) were further anchored with bilirubin and Lys-Asp-Glu-Leu grafted hyaluronic acid (HA-BR-KDEL) ligand for sequential cellular and intracellular targeting to the endoplasmic reticulum of inflammatory cells in inflamed intestinal tract. Oral delivery of HVs@HA-BR-KDEL notably alleviated colitis symptoms in mice and contributed to the restoration of intestinal homeostasis. The tea polyphenol hybrid OMV strategy holds great promise for oral gene-mediated treatment.
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Theranostics
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2022
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IF 11.6
Bohan Yin,Qin Zhang,Xinyue Xia,Chuanqi Li,Willis Kwun Hei Ho,Jiaxiang Yan,Yingying Huang,Honglian Wu,Pui Wang,Changqing Yi,Jianhua Hao,Jianfang Wang,Honglin Chen,Siu Hong Dexter Wong,Mo Yang
Background: CRISPR-Cas12a has been integrated with nanomaterial-based optical techniques, such as surface-enhanced Raman scattering (SERS), to formulate a powerful amplification-free nucleic acid detection system. However, nanomaterials impose steric hindrance to limit the accessibility of CRISPR-Cas12a to the narrow gaps (SERS hot spots) among nanoparticles (NPs) for producing a significant change in signals after nucleic acid detection. Methods: To overcome this restriction, we specifically design chimeric DNA/RNA hairpins (displacers) that can be destabilized by activated CRISPR-Cas12a in the presence of target DNA, liberating excessive RNA that can disintegrate a core-satellite nanocluster via toehold-mediated strand displacement for orchestrating a promising “on-off” nucleic acid biosensor. The core-satellite nanocluster comprises a large gold nanoparticle (AuNP) core surrounded by small AuNPs with Raman tags via DNA hybridization as an ultrabright Raman reporter, and its disassembly leads to a drastic decrease of SERS intensity as signal readouts. We further introduce a magnetic core to the large AuNPs that can facilitate their separation from the disassembled nanostructures to suppress the background for improving detection sensitivity. Results: As a proof-of-concept study, our findings showed that the application of displacers was more effective in decreasing the SERS intensity of the system and attained a better limit of detection (LOD, 10 aM) than that by directly using activated CRISPR-Cas12a, with high selectivity and stability for nucleic acid detection. Introducing magnetic-responsive functionality to our system further improves the LOD to 1 aM. Conclusion: Our work not only offers a platform to sensitively and selectively probe nucleic acids without pre-amplification but also provides new insights into the design of the CRISPR-Cas12a/SERS integrated system to resolve the steric hindrance of nanomaterials for constructing biosensors.
研究领域:
生物技术
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分析化学
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分子生物学
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高影响因子
ANALYTICAL CHEMISTRY
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2018
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IF 6.042
Yunying Cheng,Chunmei Li,Ruizhu Mu,Yuanfang Li,Tiantian Xing,Binbin Chen,Chengzhi Huang
Cellular RNA dynamics are closely associated with a vast range of physiological processes that are mostly long-lasting. To uncover the association between RNA dynamics and these processes, fluorescent RNA probes with high specificity, photostability, and biocompatibility are compulsory. Herein, a series of fluorescent carbon dots (CDs) have been prepared by one-pot hydrothermal treatment of o-, m-, or p-phenylenediamines with triethylenetetramine. Only CDs derived from the meta precursor (m-CDs) with excellent photostability and biocompatibility can specifically bind to cellular RNA, allowing successfully long-term (up to 3 days) monitoring of RNA dynamics during cell apoptosis, mitosis, and proliferation. This RNA affinity can be attributed to the isoquinoline moieties and amines on the surface of m-CDs, which can bind to RNA through π–π stacking and electrostatic bonding, respectively. The cellular internalization of m-CDs is time-, temperature-, ATP-, caveolar, and microtubule-dependent. Additionally, investigations on the in vivo behavior of m-CD suggest that they can be efficiently and rapidly excreted from the zebrafish larvae body after 48 h. Our results provide a powerful tool for clarifying complex relationships between RNA dynamics and basic biological processes, disease development, or drug interactions.
研究领域:
化学
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生物学
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分子生物学
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生物医学工程
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高影响因子
International Journal of Nanomedicine
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2022
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IF 7.033
Xiangyu Li,Shixin Zhang,Miaomiao Zhang,Ge Li,Bo Yang,Xinyue Lu,Lesheng Teng,Youxin Li,Fengying Sun
Purpose Effective therapy for rheumatoid arthritis (RA) keeps a challenge due to the complex pathogenesis of RA. It is not enough to completely inhibit the process of RA with any single therapy method. The purpose of the research is to compensate for the insufficiency of monotherapy using multiple treatment regimens with different mechanisms. Material and Methods In this study, we developed a new method to synthesize mesoporous silica nanoparticles hybridized with photosensitizer PCPDTBT (HNs). Branched polyethyleneimine-folic acid (PEI-FA) could be coated on the surface of HNs through electrostatic interactions. It simultaneously blocked the hypoxia-activated prodrug tirapazamine loaded into the mesopores and binded with Mcl-1 siRNA (siMcl-1) that interfered with the expression of the anti-apoptotic protein Mcl-1. Released from the co-delivery nanoparticles (PFHNs/TM) Tirapazamine and siMcl-1 upon exposure to acidic conditions of endosomes/lysosomes in activated macrophages. Under NIR irradiation, photothermal therapy and photodynamic therapy derived from PCPDTBT, hypoxia-activated chemotherapy derived from tirapazamine, and RNAi derived from siMcl-1 were used for the combined treatment for RA by killing activated macrophages. PEI-FA-coated PFHNs/TM exhibited activated macrophage-targeting characteristics, thereby enhancing the in vitro and in vivo NIR-induced combined treatment of RA. Results The prepared PFHNs/TM have high blood compatibility (far below 5% of hemolysis) and ideal in vitro phototherapy effect while controlling the TPZ release and binding siMcl-1. We prove that PEI-FA-coated PFHNs/TM not only protect the bound siRNA but also are selectively uptaked by activated macrophages through FA receptor-ligand-mediated endocytosis, and effectively silence the target anti-apoptotic protein by siMcl-1 transfection. In vivo, PFHNs/TM have also been revealed to be selectively enriched at the inflammatory site of RA, exhibiting NIR-induced anti-RA efficacy. Conclusion Overall, these FA-functionalized, pH-responsive PFHNs/TM represent a promising platform for the co-delivery of chemical drugs and nucleic acids for the treatment of RA cooperating with NIR-induced phototherapy.
研究领域:
纳米技术
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药学
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生物医学工程
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治疗学
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免疫学
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药物递送系统
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高影响因子
BIOSENSORS & BIOELECTRONICS
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2021
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IF 10.618
Yuqian Liu,Ruyi Li,Fangyuan Liang,Chao Deng,Farzad Seidi,Huining Xiao
Demand on the quick screening of gastric cancer (GC) has significantly stimulated the development of biomarker sensing techniques. Herein, we report the novel fluorescent paper-based analytical devices (PADs) for detections of GC-related microRNA-21 (miRNA-21) and circular RNA from Hippocampus Abundant Transcript 1 gene (circRNA-HIAT1) with prominent reliability and sensitivity. The PADs, constructed by in-situ synthesis of blue-emissive carbon dots (CDs) and conjugations of probe DNAs , exhibit the superior uniformity and stability. In the presence of targets, rolling circle amplifications (RCA) are triggered to generate long DNA strands for the assemblies of green-/red-emissive labels. Consequently, remarkable blue-to-green and blue-to-red emission color transitions of the PADs are achieved, implementing the color-analysis of miRNA-21 and circRNA-HIAT1, respectively. Benefited from the efficient RCA, coupled with the drastic ratiometric fluorescent changes, the limit of detections (LODs) of PADs are found to be several fM with the upper limit of the linear detection range at 1 nM. More importantly, the fluorescent PADs possess excellent specificity, as well as anti-interference capability in biological settings, enabling their applications in accurate GC screening with plasma samples. Overall, the proposed fluorescent PADs are featured with robust sensing platform, facile signal readout, and exceptional dual-type RNA sensing performance, holding high potential in point-of-care testing (POCT).
研究领域:
生物技术
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医学诊断
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癌症研究
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分子生物学
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PubMed
高影响因子
Journal of Cancer
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2019
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IF 3.182
Huaizeng Chen,Jia Liu,Hanzhi Wang,Qi Cheng,Caiyun Zhou,Xiaojing Chen,Feng Ye
Background and Aims: Ovarian carcinoma (OC) is one of the most lethal malignant tumors with a high reoccurrence and chemoresistance. The key mechanism relationship with chemoresistance in ovarian carcinoma is still unclear. The existence of cancer stem cells involves in chemoresistance and reoccurrence in OC. The objective of this study was to investigate the expression, suppression of malignant properties and reversal of paclitaxel resistance inhibiting RNA-binding protein Musashi-1 with siRNA in ovarian cancer cells. Methods: The expression of MSI-1 was analyzed in 39 normal ovarian epithelia tissues, 92 serous cystadenomas, 68 borderline serous cystadenomas, and 97 serous cystadenocarcinomas by immunohistochemistry. pLKO.1-MSI-1-siRNA expression vector was transfected into ovarian carcinoma cell line A2780 and its paclitaxel-resistant cell subline A2780/Taxol. The roles of MSI-1 in proliferation, apoptosis, migration and invasion were explored by cell proliferation analysis, Caspase 3 activity assay, wound healing assay, migration and matrigel invasion assay, respectively. Western Blotting and Real-time quantitative PCR were conducted to detect the expression of MSI-1 and the ERK signaling pathway. Reversal of paclitaxel resistance assay was used to evaluate the role of MSI-1 in paclitaxel resistance of OC cells. Finally, therapeutic effects of MSI-1 inhibition were investigated the xenogratfs of SCID mice in vivo of the paclitacel-resistant. Results: MSI-1 is overexpressed and associated with an unfavorable prognosis in OC patients. Knockdown of MSI-1 by small interfering RNA (siRNA) inhibits proliferation, promotes apoptosis, and reduces migration and invasion of cancer cells. Moreover, MSI-1 expression inhibition reverses paclitaxel-resistance in OC cells. We further display that MSI-1 effectively protects OC cells from paclitaxel-induced apoptosis by increasing the expression of p-Bcl-2 through ERK signaling pathway activation. In vivo , MSI-1 siRNA clearly showed a strong effect on tumor growth inhibition and paclitaxel-resistance reversal. Conclusions: These findings suggest that MSI-1 overexpression is associated with the prognosis of OC patients, and knockdown of MSI-1 can suppress malignant properties and reverse paclitaxel-resistance in OC cells. MSI-1 maybe act as a potential prognostic indicator and a therapeutic target in OC.
研究领域:
肿瘤学
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分子生物学
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癌症治疗
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高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2022
·
IF 4.369
Yuanfei Ren,Maowei Yang,Xindong Wang,Buxuan Xu,Zerong Xu,Bo Su
Diabetic osteoporosis (DOP) is a complication of diabetes mellitus (DM) and occurs due to alterations in bone metabolism under hyperglycemic condition. ELAV-like RNA binding protein 1 (ELAVL1) is abnormally up-regulated in diabetes-related diseases. Bioinformatics prediction indicates that divalent metal transporter 1 (DMT1) is a potential target of ELAVL1 . To explore the role of ELAVL1 and the involvement of ELAVL1/DMT1 axis in DOP, we established a mouse model of DM by administration of high-fat diet and intraperitoneal injection with streptozotocin (STZ). The expression of ELAVL1 and DMT1 was increased in the bone tissues of DM mice. Knockdown of ELAVL1 reduced iron level and oxidative stress , promoted osteogensis, and prevented bone mass loss, thus mitigating DOP in DM mice. In vitro , mouse pre-osteoblast MC3T3-E1 cells were treated with high glucose (25 mM) and ferric ammonium citrate (FAC, 200 μM). The inhibitory effects of ELAVL1 knockdown on iron accumulation and oxidative stress were evidenced in MC3T3-E1 cells. Knockdown of ELAVL1 enhanced osteoblast viability, differentiation and mineralization . Notably, the expression of DMT1 was positively correlated with that of ELAVL1 in vivo and in vitro . Overexpression of DMT1 abolished the effect of ELAVL1 knockdown on the behaviors of MC3T3-E1 cells, suggesting that ELAVL1 might function through regulating DMT1. In conclusion, knockdown of ELAVL1 likely alleviated DOP by inhibiting iron overload and oxidative stress and promoting osteogenesis, and DMT1 might be involved in this process. These findings provide insights into the pathogenesis of DOP and suggest a potential therapeutic target for DOP treatment.
研究领域:
内分泌学
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分子生物学
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骨代谢
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糖尿病
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骨质疏松
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PubMed
高影响因子
Autophagy
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2018
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IF 11.1
Li Yang,Bing Han,Yuan Zhang,Ying Bai,Jie Chao,Gang Hu,Honghong Yao
Endothelial-mesenchymal transition (EndoMT) is associated with damage to blood-brain barrier (BBB) integrity. Circular RNAs (circRNAs) are highly expressed in the brain and are involved in brain diseases; however, whether circRNAs regulate the EndoMT in the brain remains unknown. Our study demonstrated that circHECW2 regulated the EndoMT by directly binding to MIR30D, a significantly downregulated miRNA from miRNA profiling, which subsequently caused an increased expression of ATG5. These findings shed new light on the understanding of the noncanonical role of ATG5 in the EndoMT induced by methamphetamine (Meth) or lipopolysaccharide (LPS). The in vivo relevance was confirmed as microinjection of circHecw2 siRNA lentivirus into the mouse hippocampus suppressed the EndoMT induced by LPS. These findings provide novel insights regarding the contribution of circHECW2 to the nonautophagic role of ATG5 in the EndoMT process in the context of drug abuse and the broad range of neuroinflammatory disorders.
研究领域:
神经科学
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分子生物学
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药理学
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炎症
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PubMed
高影响因子
Cell Death & Disease
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2026
·Vol. 17
·期 1
·326
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IF 12.2
Xin Hu,Meiqi Feng,Chengjin Qi,Boran Li,Hongjuan He,Kai Li,Lu Chen,Boshu Ji,Haoran Yu,Yue Zhao,Tong Wu,Ruiheng Ma,Yuhao Dong,Yan Zhang,Qiong Wu
Investigating the epigenetic mechanisms underlying lung adenocarcinoma (LUAD) through the lens of N 4-acetylcytosine (ac4C) modification could innovate cancer treatment strategies and targets. We used biological information methods to analyze shared data, with a focus on studying N -acetyltransferase 10 (NAT10), which is the only known ac4C “writer” protein. Our analysis revealed a significant upregulation of NAT10 expression in LUAD, a finding that was corroborated by investigations in both LUAD cancer tissue samples and cell lines. Subsequently, we employed CRISPR/Cas9 technology to knock out the NAT10 gene and analyzed the resulting knockout cells using acRIP-seq and RNA-seq techniques. Our findings demonstrated different expressions of the genes C-X-C motif chemokine ligand 5 (CXCL5) and DEK proto-oncogene (DEK), and functional enrichment analysis indicated a strong association with the adhesion signaling pathway. Laboratory experiments revealed that NAT10 acts as an ac4C “writer,” promoting the acetylation of CXCL5 and DEK and thus preventing the degradation of their mRNAs. Moreover, NAT10 was found to significantly affect the number of metastases and tumor growth following the injection of cancer cells into the tail vein of mice. Our research data suggests that targeting NAT10 has the potential to serve as a diagnostic biomarker or prognostic target for developing anti-metastatic therapies aimed at disrupting the adhesion process.
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ANTI-CANCER DRUGS
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2023
·
IF 2.3
Wang Guangxin,Gao Xia,Sun Zhijun,He Tianyou,Huang Chaogang,Li Shouwei,Long Haocheng
Enhancing research indicatedthat circular RNA (circRNA) acted a critical part in cholangiocarcinoma (CHOL) development. This research aims to discover the role of circRNA SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 ( SMARCA5 ) in CHOL bio-progression, which has been proved to be downregulated in CHOL tissues. In this study, quantitative reverse transcription polymerase chain reaction was used to reveal the level and linkage of circRNA SMARCA5 , miRNA-95-3p and TNF receptor-associated factor 3 gene ( TRAF3 ) in CHOL tissues and cancer cells. The target sites of circRNA SMARCA5 and miRNA-95-3p were forecast by Starbase, and Targetscan was conducted to forecast the potential linkage points of TRAF3 and miRNA-95-3p , and which is affirmed by double luciferase reporter assay. CCK-8 and flow cytometry assay was carried to indicate cell viability. And apoptosis-related protein was counted by caspase3 activity and Western blot assay. CircRNA SMARCA5 was downregulated in CHOL cell lines and cancer samples. Besides, over-expression of SMARCA5 inhibited cell growth and promoted apoptotic rate. Dual-luciferase reporter assays presented that miRNA-95-3p could link with circRNA SMARCA5 . Moreover, miRNA-95-3p was discovered highly expressed in CHOL. Interference of miRNA-95-3p repressed cell proliferation and raised the apoptosis. Importantly, TRAF3 was validated to be a downstream of miRNA-95-3p . Strengthen of miRNA-95-3p reversed the inhibitory impact of circRNA SMARCA5 -plasmid transfection, and the results of miRNA-95-3p inhibitor were reversed by si- TRAF3 . CircRNA SMARCA5 is involved in CHOL development by interosculating miRNA-95-3p / TRAF3 axis and may become a novel approach for treating CHOL.
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JOURNAL OF HAZARDOUS MATERIALS
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2023
·
IF 13.6
Renzhang Lin,Hao Wu,Xiangyu Kong,Hao Ren,Zhenmei Lu
The lack of universal indicators for predicting microbial biodegradation potential and assessing remediation effects limits the generalization of bioremediation. The community-level ribosomal RNA gene operon (rrn) copy number, an important functional trait, has the potential to serve as a key indicator of the bioremediation of organic pollutants . A meta-analysis based on 1275 samples from 26 hydrocarbon-related studies revealed a positive relationship between the microbial hydrocarbon biodegradation level and the community-level rrn copy number in soil, seawater and culture. Subsequently, a microcosm experiment was performed to decipher the community-level rrn copy number response mechanism during total petroleum hydrocarbon (TPH) biodegradation. The treatment combining straw with resuscitation-promoting factor (Rpf) exhibited the highest community-level rrn copy number and the most effective biodegradation compared with other treatments, and the initial TPH content (20,000 mg kg -1 ) was reduced by 67.67% after 77 days of incubation. TPH biodegradation rate was positively correlated with the average community-level rrn copy number ( p = 0.001, R 2 = 0.5781). Both meta and community analyses showed that rrn copy number may reflect the potential of hydrocarbon degradation and microbial dormancy. Our findings provide insight into the applicability of the community-level rrn copy number to assess bacterial biodegradation for pollution remediation.
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