Asian Journal of Pharmaceutical Sciences
·
2026
·
IF 11.9
Jingjing Su,Wenguang Huang,Wenying Zhang,Ziyi Wang,Hongzhou Gu,Pengchao Sun,Yongxing Zhao
Rheumatoid arthritis (RA) as a systemic autoimmune disease, frequently triggers various extra-articular symptoms, particularly the RA-associated pneumonia. Unfortunately, the RA-associated pneumonia has garnered insufficient attention, and conventional RA therapies may exacerbate pneumonia-related complications, thereby complicating the treatment process. Herein, a novel dual immunoregulatory mRNA nanovaccine (MPDA@RC@HM) is designed for the efficient treatment of RA and RA-associated pneumonia simultaneously. This innovative mRNA nanovaccine represents a highly organized nanostructure that integrates the rapamycin-loaded mesoporous polydopamine (MPDA) with mRNA encoding the epitope of type Ⅱ collagen, and the surface is modified with hyaluronic acid and dendritic cell membrane. After intravenous injection into collagen-induced arthritis mice, the mRNA nanovaccine exhibits effective distribution and transfection within the spleen and lung, subsequently exerting potent immunoregulation in both organs, thereby yielding a dual therapeutic effect. This study presents a versatile mRNA nanovaccine platform for the treatment of autoimmune diseases and provides an innovative approach for addressing RA and RA-associated pneumonia.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
eLife
·
2026
·
IF 0
Hai-Qian Zhou,Zhen Zhu,Jia-Wei Zhang,Wei-Peng Lin,Hao-JY Jin,Yang-Yang Ding,Shuai Liu,Dong-Min Yin
Precise regulation of protein synthesis is critical for brain functions such as long-term memory, and its dysregulation is implicated in numerous memory disorders. While mRNA methylation, such as N6-methyladenosine (m6A), has been widely studied in memory, the role of mRNA acetylation remains largely unknown. N4-acetylcytidine (ac4C), the only known form of RNA acetylation in eukaryotes, promotes mRNA stability and translation. In this study, we identified the ac4C epitranscriptome in mouse hippocampal homogenates and synaptosomes through ac4C-RNA immunoprecipitation followed by next-generation sequencing (acRIP-seq). The Morris water maze was employed to induce and evaluate memory acquisition and forgetting processes. We show that synaptic ac4C levels are dynamically regulated, increasing after memory formation and returning to baseline after natural forgetting. The dynamic changes of ac4C-mRNAs regulated by memory were validated by ac4C dot-blot, liquid chromatography–tandem mass spectrometry, and acRIP-qPCR analysis. We further demonstrate that N-acetyltransferase 10, the ac4C writer, in mouse hippocampus is important for spatial memory via regulating memory-related mRNAs, proteins, and ultimately synaptic plasticity. Lastly, we generated a freely accessible website (http://ac4catlas.com) that included the dataset of ac4C epitranscriptome in mouse hippocampus. Altogether, these results demonstrate that dynamic and localized mRNA acetylation is important for synaptic plasticity and memory.
✓ 已验证
产品关联
DOI
PubMed
Science Bulletin
·
2026
·
IF 20.7
Yi Song,Zhangchi Dongye,Jiaxi Yao,Xiaonan Zhao,Tao Mo,Shiyu Yang,Cong Sun,Tingting Zhao,Jian Li,Yuzhang Wu
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Current non-specific immunosuppressive therapies carry risks of infection and malignancy. Antigen-specific tolerance induction presents a promising alternative. Here, we developed a messenger RNA-lipid nanoparticle (mRNA-LNP) vaccine (LiH-LNPs) encoding a tandem fusion of epitopes from three MS-associated myelin antigens. LiH-LNPs alleviated inflammatory infiltration and demyelination in experimental autoimmune encephalomyelitis (EAE). Single-cell RNA sequencing revealed that LiH-LNPs reshaped the spinal cord microenvironment toward inflammation resolution by reducing the abundance and inflammatory activity of infiltrating myeloid cells and activated microglia, inducing apoptosis of encephalitogenic T cells while increasing regulatory T (Treg) cell abundance and suppressive activity. These findings provide mechanistic insights into antigen-specific immunotherapy for MS and highlight the potential application of mRNA vaccine-based antigen-specific therapy for autoimmune diseases. Download: Download high-res image (292KB) Download: Download full-size image
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-23
·
IF 17.694
Hao WeiChao,Dian MeiJuan,Zhou Ying,Zhong QiuLing,Pang WenQian,Li ZiJian,Zhao YaYan,Ma JiaCheng,Lin XiaoLin,Luo RenRu,Li YongLong,Jia JunShuang,Shen HongFen,Huang ShiHao,Dai GuanQi,Wang JiaHong,Sun Yan,Xiao Dong
Autophagy is crucial for maintaining cellular energy homeostasis and for cells to adapt to nutrient deficiency, and nutrient sensors regulating autophagy have been reported previously. However, the role of eiptranscriptomic modifications such as m 6 A in the regulation of starvation-induced autophagy is unclear. Here, we show that the m 6 A reader YTHDF3 is essential for autophagy induction. m 6 A modification is up-regulated to promote autophagosome formation and lysosomal degradation upon nutrient deficiency. METTL3 depletion leads to a loss of functional m 6 A modification and inhibits YTHDF3-mediated autophagy flux. YTHDF3 promotes autophagy by recognizing m 6 A modification sites around the stop codon of FOXO3 mRNA. YTHDF3 also recruits eIF3a and eIF4B to facilitate FOXO3 translation, subsequently initiating autophagy. Overall, our study demonstrates that the epitranscriptome regulator YTHDF3 functions as a nutrient responder, providing a glimpse into the post-transcriptional RNA modifications that regulate metabolic homeostasis.
研究领域:
细胞生物学
·
分子生物学
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Lei huang,Siyuan Tang,Jiachen Guo,Yixing Tu,Sian Li,Taihua Yang,Dong Zhao,Chao Wang
Localized delivery of mRNA-based therapies has shown promise in cancer treatment, but challenges such as drug leakage and systemic toxicity remain. This study aimed to develop a locally retained lipid nanoparticle (LNP) system for the co-delivery of mRNA and the photosensitizer indocyanine green (ICG) to treat superficial tumors. By systematically optimizing the lipid composition and mRNA-to-ICG ratio, we achieved high encapsulation efficiency and localized protein expression. The LNP system demonstrated robust transfection efficiency and photothermal effects, with minimal off-target distribution. In vivo studies revealed significant tumor growth inhibition, highlighting the potential of this approach for localized cancer therapy. This study provides a novel strategy for the co-delivery of mRNA and photosensitizers, offering a promising avenue for the treatment of superficial tumors with minimal systemic exposure.
研究领域:
癌症研究
·
纳米医学
·
药剂学
·
分子治疗
✓ 已验证
产品关联
DOI
高影响因子
Small Methods
·
2023
·
IF 12.4
Jianhai Chen,Jianwei Tan,Jian Li,Wenxiang Cheng,Liqing Ke,Anqiao Wang,Qiqing Wang,Sien Lin,Gang Li,Benguo Wang,Jingqin Chen,Peng Zhang
In addition to inhibiting persistent inflammation, phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is known as an important therapeutic target for alleviating rheumatoid arthritis (RA) symptoms. Modulation of PTEN gene expression in synovial tissue using messenger RNA (mRNA) is a promising approach to combat RA. However, mRNA therapeutics are often hampered by unsatisfactory stability and inefficient localization in synovial tissue. In this study, a genetically engineered biomimetic membrane-coated mRNA (MR@P-mPTEN) carrier that effectively delivers mRNA-PTEN (mPTEN) directly to the RA joint is presented. By overexpressing tumor necrosis factor (TNF-α) receptors on macrophage biomimetic membranes via plasmid transfection, decoys that reduce inflammatory pathway activation are prepared for TNF-α. The resulting construct, MR@P-mPTEN, shows good stability and RA targeting based on in vivo fluorescence imaging. It is also found that MR@P-mPTEN competitively binds TNF-α and activates the PTEN pathway in vitro and in vivo, thereby inhibiting synovitis and joint damage. Clinical micro-computed tomography and histological analyses confirm the treatment effects. These results suggest that the genetically engineered biomimetic therapeutic platform MR@P-mPTEN both inhibits pro-inflammatory cytokines and upregulates PTEN protein expression to alleviate RA damage, providing a new a new combination strategy for RA treatment.
研究领域:
生物技术
·
药理学
·
分子生物学
·
纳米技术
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2020
·
IF 5.186
Zhang Yan,Wang Yanfei,Yao Xuebo,Wang Changquan,Chen Fangyi,Liu Dong,Shao Ming,Xu Zhigang
Hair cells in the inner ear and lateral lines are mechanosensitive receptor cells whose development and function are tightly regulated. Several transcription factors as well as splicing factors have been identified to play important roles in hair cell development, whereas the role of RNA stability in this process is poorly understood. In the present work, we report that RNA-binding motif protein 24a (Rbm24a) is indispensable for hair cell development in zebrafish. Rbm24a expression is detected in the inner ear as well as lateral line neuromasts. Albeit rbm24a deficient zebrafish do not survive beyond 9 days post fertilization (dpf) due to effects outside of the inner ear, rbm24a deficiency does not affect the early development of inner ear except for delayed otolith formation and semicircular canal fusion. However, hair cell development is severely affected and hair bundle is disorganized in rbm24a mutants. As a result, the auditory and vestibular function of rbm24a mutants are compromised. RNAseq analyses identified several Rbm24a-target mRNAs that are directly bound by Rbm24a and are dysregulated in rbm24a mutants. Among the identified Rbm24a-target genes, lrrc23, dfna5b, and smpx are particularly interesting as their dysregulation might contribute to the inner ear phenotypes in rbm24a mutants. In conclusion, our data suggest that Rbm24a affects hair cell development in zebrafish through regulating mRNA stability.
研究领域:
发育生物学
·
分子生物学
·
神经科学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2021
·
IF 5.037
Rui Huang,Qixia Yang,Tiantian Wang
Aims Norcantharidin (NCTD) exhibits antitumor, anti-inflammatory, and anti-fibrosis properties, which makes NCTD an attractive candidate for the treatment of pathological scars. This study was designed to investigate the potential effects of NCTD on fibroblast proliferation and explore the underlying mechanisms. Materials and methods First, cell viability and cell apoptosis were evaluated to determine the effects of NCTD on human skin fibroblasts, at 10, 50, and 100 μM. To explore the mechanism, bioinformatics analyses, chromatin immunoprecipitation, RNA immunoprecipitation, and RNA pulldown assays, and luciferase reporter assays were performed to verify the relationships among NCTD, signal transducer and activator of transcription 3 (STAT3), annexin A2 pseudogene 2 (ANXA2P2), and ubiquitin-associated protein 2-like (UBAP2L) mRNA in fibroblasts. Loss-of-function experiments were performed to investigate the roles played by STAT3, ANXA2P2, and UBAP2L in the proliferation and apoptosis of fibroblasts. Key findings We found that NCTD administration induced fibroblast apoptosis and inhibited fibroblast proliferation in a dose-dependent manner. Mechanistically, NCTD inhibited ANXA2P2 transcription through the inhibition of STAT3 phosphorylation. Subsequently, ANXA2P2 was found to enhance the physical interaction between UBAP2L mRNA and lin-28 homolog B (LIN28B), which increased the stability and levels of UBAP2L mRNA. Loss-of-function assays demonstrated that ANXA2P2 and UBAP2L knockdown induced fibroblast apoptosis and suppressed fibroblast proliferation. Significance In conclusion, we confirmed that NCTD inhibits fibroblast proliferation by inhibiting the STAT3/ANXA2P2/UBAP2L axis, which suggested that NCTD could represent a new candidate for the treatment of pathological scars.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2024
·
IF 12.4
Yixuan Huang,Jiacai Wu,Sanpeng Li,Zhen Liu,Zhenghua Li,Boping Zhou,Bin Li
Background: As the overwhelming majority of advanced mRNA delivery systems are preferentially accumulated in the liver, there is an accelerating growth in the demand for the development of non-liver mRNA delivery platforms. Methods: In this study, we prepared cationic lipid-like nanoassemblies through a N-quaternizing strategy. Their physicochemical properties, in vitro mRNA delivery efficiency, and organ tropism in mice were investigated. Results: Introduction of quaternary ammonium groups onto lipid-like nanoassemblies not only enhances their mRNA delivery performance in vitro, but also completely alters their tropism from the spleen to the lung after intravenous administration in mice. Quaternized lipid-like nanoassemblies exhibit ultra-high specificity to the lung and are predominantly taken up by pulmonary immune cells, leading to over 95% of exogenous mRNA translation in the lungs. Such mRNA delivery carriers are stable even after more than one-year storage at ambient temperature. Conclusions: Quaternization provides an alternative method for design of new lung-targeted mRNA delivery systems without incorporation of targeting ligands, which should extend the therapeutic applicability of mRNA to lung diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2023
·
IF 4.7
Zhikai Liu,Mei Yang,Wang Yao,Tingting Wang,Guangwen Chen
Controllable and scalable synthesis of biomedical organic nanoparticles (NPs) with tailored properties is critical for their clinical translation. However, the existing microfluidics-based synthesis is challenged by clogging and limited throughput, while the traditional ultrasound-assisted synthesis suffers from inhomogeneous cavitation activity, leading to wide particle size distribution. Herein, a series of biomedical organic NPs were successfully synthesized in a controlled, clog-free and scalable manner via a versatile microfluidic ultrasonic cavitation (MUC) approach. First, the effects of microchannel dimension and operating conditions on ultrasonic cavitation behavior and mixing performance was systematically studied. Cavitation pattern maps were developed for different operating conditions. By adjusting microchannel dimension and operating parameters, rapid mixing on a millisecond scale can be accomplished across an extensive range of conditions, including flow rates between 4 and 24 mL/min and flow rate ratios from 5:1 to 1:1. Then, the MUC approach was utilized to synthesize polymeric NPs, lipopolymeric NPs and lipid NPs encapsulating mRNA (mRNA-LNP). Compared to traditional microfluidics and ultrasound-based methods, NPs synthesized by MUC approach showed smaller sizes and more uniform distributions. The ability of MUC approach for clog-free and scalable production was demonstrated by the continuous synthesis of lipopolymeric NPs at a throughput of 1.6 g/h with desired properties. The successful synthesis of soft and fragile mRNA-LNPs has been accomplished by tailoring the cavitation pattern of MUC approach. The resultant mRNA-LNPs showed a mRNA encapsulation rate as high as 98.3%, over 99% transfection efficiency of cell with 0.5 μg dosage, and robust luciferase expression with 10 μg dosage at the injection site of BALB/c mice 24 h after injection.
研究领域:
纳米技术
·
生物医学工程
·
药物递送
✓ 已验证
产品关联
DOI
高影响因子
Advanced NanoBiomed Research
·
2025
·
IF 4.4
Kexin Deng,Juping Sun,Junyu Liu,Yuqi Zhang,Wanwan Liu,Xiaobin Li,Han Wu,Juan Li,Jisong Zhang,Chanyuan Jin,Can Yang Zhang
Despite triple-negative breast cancer (TNBC) is the most heterogeneous and aggressive subtype of breast cancer, immunotherapy is emerging as a promising therapy. Here, a mannose-modified cationic liposome (cLipo)-based mRNA therapeutics with dendritic cell (DC) targeting and high safety is developed for TNBC immunotherapy. The cLipos are fabricated using mannose-modified PEGylated lipids, DOPE, DOTAP, and cholesterol, followed by systematic screening of formulations based on mRNA loading capacity, cytotoxicity, and transfection efficacy. The mTEM8, which is related to tumor endothelial marker 8 (TEM8, known as Anthrax Toxin Receptor 1), can be efficiently encapsulated into the optimal cLipo to prepare the mRNA therapeutics (cLipo-Man/mTEM8), which can deliver mTEM8 to DCs with an eightfold higher delivery efficiency compared with the commercial Liposomes. The cLipo-Man/mTEM8 therapeutics elicited robust immune activation, significantly enhancing CD4 + and CD8 + T-cell responses and improving antitumor efficacy in TNBC-bearing mice. The tumor growth of TNBC-bearing mice treated with the cLipo-Man/mTEM8 therapeutics is obviously suppressed, and the survival rate is doubled compared to other controls. Furthermore, the mannose-modified cLipo system demonstrated excellent biosafety in vivo. Collectively, this study presents a safe and effective mannose-modified cLipo-based mRNA therapeutic with strong potential for advancing TNBC immunotherapy.
研究领域:
肿瘤学
·
免疫治疗
·
纳米医学
·
分子生物学
·
药物递送
✓ 已验证
产品关联
DOI
高影响因子
CELL RESEARCH
·
2026
·
IF 25.9
Liao Kun,Cao Fen,Wei Chen,Qian Zheng-Yu,Hu Hong-Rong,Pan Wen-Feng,Feng Zi-Qing,Lian Sen-mao,Xiao Zi-Xuan,Sheng Hui,Mo Hai-Yu,Zhao Yi-Xuan,Wu Qi-Nian,Zeng Zhao-Lei,Li Bo,Xu Rui-Hua,Ju Huai-Qiang
Methionine metabolism generates the substrate S-adenosylmethionine (SAM), which regulates epigenetic modifications crucial for various cellular processes, particularly tumorigenesis. However, whether methionine metabolism involves epigenetic mechanisms independent of SAM and what roles such mechanisms play in tumorigenesis remain unclear. We show here that the adenosylhomocysteinase (AHCY)–adenosine complex increases mRNA m 6 A levels in a non-global manner, promoting fatty acid synthesis and tumorigenesis. Adenosine increases mRNA m 6 A levels by binding to the methionine metabolism enzyme AHCY to form a complex, rather than depending on adenosine receptors. The AHCY–adenosine complex facilitates AHCY dimerization, with adenosine being crucial for dimer stability. AHCY dimers hinder the binding of fat mass and obesity-associated protein (FTO) at the Q86 site to RNA containing the VWDRACH motif, increasing m 6 A levels and upregulating lipogenesis genes, especially ACACA and SCD1, thus leading to reprogramming of lipid metabolism. Conversely, AHCY mutants that have lost dimerization or FTO-binding ability but retain hydrolase activity suppress lipogenesis and tumor growth without significantly affecting methionine catabolism mediated by AHCY. Loss of AHCY in mice and disruption of AHCY dimerization in tumor cells and patient-derived xenograft models restricted tumor growth. Our findings demonstrate a key SAM-independent link between methionine metabolism and mRNA m 6 A modification that affects demethylase substrate specificity. This novel link between the methionine cycle and lipid metabolism suggests new strategies for anticancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）