FISH & SHELLFISH IMMUNOLOGY
·
2026
·
IF 4.2
Yujun Liu,Gengrong Zhang,Haozhe Qu,Ziyu Hu,Maosheng He,Fei Ling,Gaoxue Wang,Tianqiang Liu
The mRNA vaccine can induce specific antibodies in Largemouth bass. • mRNA Cap (1) and poly (A) mRNA reduce RIG-I recognition of foreign mRNA in Largemouth bass. • The mRNA vaccine triggered a rapid immune response in bony fish. • Improved the survival rate of largemouth bass to 57% in LMBV infection. Largemouth bass virus (LMBV) infection poses a significant threat to largemouth bass farming in China, yet effective and safe vaccines remain scarce. In this study, we designed and evaluated four mRNA vaccine candidates against LMBV, all encoding the viral major capsid protein (MCP). The fully configured construct (LMUM) contained a 5′ cap1, untranslated regions (UTRs), and a poly(A) tail, and was produced by in vitro transcription. Each mRNA was encapsulated into lipid nanoparticles (LNPs), yielding homogeneous particles (∼110 nm diameter, ∼54 mV zeta potential) with >96% encapsulation efficiency that provided substantial protection against RNase degradation (43% of mRNA remained intact in LNP-encapsulated groups versus 10% in unprotected controls). Intramuscular immunization of largemouth bass with LNP-encapsulated LMUM (0.2 μg/g body weight) induced MCP-specific serum antibodies after primary immunization, with a strong booster response after the second dose. In the LMUM-immunized group, spleen mRNA levels of IgM and CD4 were upregulated 3.4-fold and 3.2-fold, respectively, by day 14, while the groups lacking UTR or cap/poly(A) tail failed to induce these adaptive immune markers. Interestingly, the incomplete constructs triggered stronger activation of the RIG-I pathway (RIG-I, MAVS, TBK1) than the fully modified LMUM, suggesting that the combination of cap1, UTR, and poly(A) tail helps dampen excessive innate sensing. Following a lethal LMBV challenge, the LMUM vaccine conferred 45–50% relative survival after primary immunization, which increased to 53–57% after the booster dose. In contrast, the incomplete vaccine constructs and naked mRNA gave only 10–15% survival, and control groups experienced nearly complete mortality. These results demonstrate that a fully modified mRNA-LNP vaccine against LMBV induces robust humoral and cellular immune responses and provides significant protective efficacy in largemouth bass.
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高影响因子
JOURNAL OF TOXICOLOGICAL SCIENCES
·
2019
·
IF 1.732
Nana Long,Huaqiao Tang,Lin Lin,Jianlong Li,Lijuan Guo,Fenghui Sun,Min Dai
Methicillin-resistant Staphylococcus aureus (MRSA) leads to serious infections, but it is not known whether it changes the expression of kidney drug metabolizing enzymes during infection. The mice were infected with different doses of MRSA and the oxidative stress and inflammation levels in the kidney were examined. The mRNA expression and activity of cytochrome P450 enzyme was analysed. Mice infected with high levels of MRSA showed a decrease in renal antioxidant capability and an elevated level of oxidative metabolites, which was accompanied by the release of inflammatory cytokines. The levels of interleukin 1β, tumour necrosis factor alpha, and macrophage inflammatory protein-1α were significantly increased along with the levels of nitric oxide and malondialdehyde. On day 7, mRNA expression of Cyp1a2, 2d22, and 3a11 were decreased by the high level of MRSA, but the low level of MRSA increased their expressions. Cyp2e1 mRNA expression was increased by MRSA in the kidney of mice. High dose of MRSA infection increased the oxidative stress and inflammatory response in mouse kidney, leading to the decrease in the expression of renal drug-metabolizing enzymes and no recovery within 7 days.
研究领域:
药理学
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微生物学
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病理学
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高影响因子
Human Cell
·
2025
·Vol. 38
·期 3
·1-14
·
IF 3.1
Zhu Xiao-Yu,Li Pi-Song,Qu Hui,Ai Xing,Zhao Zi-Ting,He Jia-Bei
Radiotherapy resistance, is usually caused by enhanced tumor stemness and poses a significant challenge in treating breast cancer (BRCA). In this study, we investigated the molecular regulatory mechanism of radiotherapy sensitivity in BRCA associated with replication factor C4 (RFC4) and insulin-like growth factor 2 mRNA binding protein 2 mRNA Binding Protein 2 (IGF2BP2). RFC4 expression was increased in BRCA cell lines and tissues, and high RFC4 expression in BRCA patients predicted the occurrence of lymphatic metastasis. RFC4-specific short hairpin RNA sequences or RFC4 coding sequences were subsequently cloned and inserted into plasmid vectors to downregulate or upregulate RFC4 expression. Knockdown of RFC4 attenuated stemness, as evidenced by a reduction in sphere formation and the downregulation of CD44 and SOX2. RFC4 silencing inhibited migration and invasion, promoted apoptosis, and improved sensitivity to radiotherapy (4-Gy X-ray). The results were detected by a wound healing assay, a transwell assay, and flow cytometry. The overexpression of RFC4 had the opposite effect on BRCA cells. Like RFC4 expression, IGF2BP2 expression was also increased in the cancer tissues of breast cancer patients. The results of the dual luciferase assay and RIP assay confirmed the binding of IGF2BP2 to the RFC4 mRNA coding sequence. Knockdown of RFC4 eliminated the effects of IGF2BP2 overexpression on increasing cell viability, invasion, the expression of stemness markers and radioresistance, suggesting that the effect of RFC4 on the stemness of BRCA cells was regulated by IGF2BP2. In conclusion, we reported that RFC4, a key regulator of BRCA progression, promoted radioresistance in BRCA and was positively regulated by IGF2BP2.
研究领域:
肿瘤学
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分子生物学
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医学
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高影响因子
PULMONARY PHARMACOLOGY & THERAPEUTICS
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2024
·
IF 3.3
Huijuan Zhang,Jianli Qiu,Qianyi Zhao,Yong Zhang,Haitao Zheng,Ziying Dou,Yongbin Yan
Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased. HE and Masson staining revealed that pathological symptoms of lung histopathology were relieved after Zbtb16 knockdown. Protein expressions of α-SMA, Collagen I and Fibronectin were significantly decreased after Zbtb16 knockdown in vivo and in vitro . Meanwhile, the protein content of TGF-β1 and the phosphorylation of Smad2/3 were inhibited by Zbtb16 knockdown. Conversely, under the treatment of Tan IIA and TGF-β1, overexpression of Zbtb16 improved cell viability, increased the expression of fibrosis-related proteins, and promoted the phosphorylation of Smad 2/3. All above demonstrates that Zbtb16 inhibition ameliorates pulmonary fibrosis and suppresses the TGF-β/Smad pathway. Furthermore, Zbtb16 mediates the inhibitory process of Tan IIA on pulmonary fibrosis. This study provides a novel candidate therapeutic target for pulmonary fibrosis.
研究领域:
药理学
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肺病学
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分子生物学
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病理学
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高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
MingJu Chen,Yuxiao Wu,Hongxuan Yang,Tianfeng Liu,Tongkun Han,Wangqiang Dai,Junyue Cen,Fan Ouyang,Jingjing Chen,Jianxin Liu,Lin Zhou,Xuguang Hu
Introduction: This study aimed to establish a fermentation system based on Lactobacillus casei (LC) and Arctium lappa L. root (AR) to investigate its effects. The objectives included comparing metabolite profiles pre- and post-fermentation using untargeted metabolomics and evaluating the impact of LC-AR in high-fat diet-induced hyperlipidemic mice.Methods: Untargeted metabolomics was used to analyze differences in metabolites before and after fermentation. In vitro antioxidant activity, liver injury, lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA expression were assessed. 16S rRNA sequencing was conducted to evaluate changes in gut microbiota composition.Results: LC-AR exhibited stronger antioxidant activity and higher metabolite levels than AR. It also improved liver injury as well as better regulation of lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA. 16S rRNA analysis revealed that LC-AR decreased the Firmicutes/Bacteroidetes ratio, which correlated negatively with triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels.Discussion: These findings suggest that LC-AR may serve as a promising functional food and drug raw material for improving hyperlipidemia, particularly through its beneficial effects on gut microbiota and lipid regulation.
研究领域:
药理学
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营养学
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微生物学
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代谢组学
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Frontiers in Oncology
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2022
·
IF 5.738
Youfu Zhang,Xuyang Wang,Huaxiang Wang,Yi Jiang,Zhidan Xu,Laibang Luo
Background Elevated Small Nuclear Ribonucleoprotein Polypeptide A ( SNRPA ) can enhance tumor cell growth and proliferation in various cancers. However, rarely studies focus on the comprehensive analysis of SNRPA in hepatocellular carcinoma (HCC). Methods TCGA and GEO databases were used to analyze the mRNA expression of SNRPA in HCC. Protein expression of SNAPA was validated using immunohistochemistry. Stably transfected HCC cells were used to investigate the role of SNRPA in the progression of HCC. The functional enrichment analysis was utilized for the biological function prediction. The CIBERSORT and ssGSEA algorithms were used to evaluate the composition of the tumor microenvironment and immunocyte infiltration ratio. Results The SNRPA expression was upregulated in HCC and positively correlated with tumor stage and grade. SNRPA overexpression were independent risk factors for poor overall survival (OS) and recurrence-free survival (RFS). In patients with early-stage disease, low alpha-fetoprotein expression, and better differentiation, SNRPA still exhibited the excellent prognostic value. Knockdown of SNRPA inhibited the proliferation and migration while promoting the apoptosis of HCC cells. Higher methylation of the CpG site cg16596691 correlated with longer OS in HCC patients. Genes co-expressed with SNRPA were overexpressed in HCC and correlated with shorter OS. The GO and KEGG enrichment analysis showed that SNRPA expression was related to mRNA splicing, spliceosome signaling. GSEA demonstrated that the main enrichment pathway of SNRPA-related differential genes was spliceosome signaling, cell cycle signaling, P53 signaling pathway, T cell receptor signaling pathway, natural killer cell-mediated signaling. CIBERSORT and ssGSEA algorithm revealed that SNRPA was mainly associated with the higher proportion of CD8+T cells, T cells follicular helper, T cells regulatory, Macrophages M0, and the lower proportion of T cells CD4 memory resting, NK cells resting, Monocytes, and Mast cells resting. Conclusion Elevated SNRPA enhances tumor cell proliferation and correlated with poor prognosis and immune infiltrates in patients with HCC.
研究领域:
肿瘤学
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分子生物学
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免疫学
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生物信息学
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ANALYTICA CHIMICA ACTA
·
2020
·
IF 5.977
Hongyan Jiang,Qing Xia,Daojun Liu,Kai Ling
Many polymer decorated/modified 2D nanomaterials have been developed as enhanced drug delivery systems and photothermal theranostic nanoagents. However, few reports describe the use of these novel nanomaterials as nanoplatforms for biomolecule sensing. Herein, we used calcium-cation-doped polydopamine-modified (PDA-modified) 2D black phosphorus (BP) nanosheets ( [email protected] ) as a sensing nanoplatform for the detection of nucleic acids and proteins in complex biological samples. Fluorescent-dye-labeled single-strand DNA aptamer/probes are adsorbed by the Ca 2+ -doped [email protected] mediated by calcium-cation coordination. The PDA coating enhances the stability of the inner BP, provides binding sites to DNA nucleobases, and quenches fluorescence. Without any chemical conjugation, this sensing nanoplatform selectively and specifically detects protein (human thrombin, linear range: 10–25 nM, detection limit: 0.02 nM), single-strand DNA (linear range: 1–10 nM, detection limit: 0.52 nM) in 1% serum diluted samples, and senses intracellular mRNAs (C-myc, and actin) in living cells. The nanoplatform exhibits the advantages of both the 2D nanomaterial (BP) and the coating polymer (PDA), naturally enters living cells unaided by transfection agents, resists enzymatic lysis and shows high biocompatibility. This nanoplatform design contributes towards future biomolecule analytical method development based on polymer decorated/modified 2D nanomaterials.
研究领域:
纳米技术
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生物传感
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材料科学
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分析化学
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高影响因子
Advanced Healthcare Materials
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2024
·
IF 10
Hao Fang,Tingting Wang,Jun Dai,Jing-Jing Hu,Zhaojun Chen,Lizhen Yuan,Yuning Hong,Fan Xia,Xiaoding Lou
Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1 O 2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.
研究领域:
癌症生物学
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分子生物学
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治疗学
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光动力疗法
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蛋白质组学
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高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Yi Wang,Nahui Liu,Lifan Hu,Jingsong Yang,Mengmeng Han,Tianjiao Zhou,Lei Xing,Hulin Jiang
Leber’s hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing it. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON. The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer, along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process. In a mouse model induced with a complex I inhibitor (rotenone, Rot), mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity (76.5%) compared to the group exposed to Rot damage (29.5%), which greatly promoted the restoration of ATP generation and mitigation of ocular mitochondrial disease-related phenotypes. This study highlights the significance of nanoengineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.
研究领域:
眼科学
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线粒体生物学
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纳米技术
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治疗学
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高影响因子
JOURNAL OF GENERAL VIROLOGY
·
2024
·Vol. 105
·期 5
·001996
·
IF 3.6
Yuting Duan,Haichuan Li,Shuai Huang,Yaoming Li,Shuyi Chen,Lilan Xie
Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, has caused huge economic losses to the pig industry, with 100% mortality in piglets aged 2 weeks and intestinal injury in pigs of other ages. However, there is still a shortage of safe and effective anti-TGEV drugs in clinics. In this study, phloretin, a naturally occurring dihydrochalcone glycoside, was identified as a potent antagonist of TGEV. Specifically, we found phloretin effectively inhibited TGEV proliferation in PK-15 cells, dose-dependently reducing the expression of TGEV N protein, mRNA, and virus titer. The anti-TGEV activity of phloretin was furthermore refined to target the internalization and replication stages. Moreover, we also found that phloretin could decrease the expression levels of proinflammatory cytokines induced by TGEV infection. In addition, we expanded the potential key targets associated with the anti-TGEV effect of phloretin to AR, CDK2, INS, ESR1, ESR2, EGFR, PGR, PPARG, PRKACA, and MAPK14 with the help of network pharmacology and molecular docking techniques. Furthermore, resistant viruses have been selected by culturing TGEV with increasing concentrations of phloretin. Resistance mutations were reproducibly mapped to the residue (S242) of main protease (Mpro). Molecular docking analysis showed that the mutation (S242F) significantly disrupted phloretin binding to Mpro, suggesting Mpromight be a potent target of phloretin. In summary, our findings indicate that phloretin is a promising drug candidate for combating TGEV, which may be helpful for developing pharmacotherapies for TGEV and other coronavirus infections.
研究领域:
病毒学
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药理学
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分子生物学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhicheng Le,Jiang Qian,Haolin Chen,Zepeng He,Runcheng Tan,Hong Liu,Zhenfu Wen,Yi Shi,Zhijia Liu,Yongming Chen
Encouraging results from clinical trials have underscored the potential of gene-pulsed dendritic cell (DC) vaccines as a viable approach for immunotherapy. However, insufficient gene delivery and functional deficiencies in antigen presentation, migratory capacity and cytokine release of DC vaccines limited its broader clinical application. Here, a combinatorial design of cationic gemini amphiphile (GA) molecular library based on the four-component Ugi reaction (Ugi-4CR) has been developed to identify versatile non-viral vectors for gene-engineered DC vaccines. We demonstrated that the leading GA enabled robust transfection of plasmid DNA or mRNA into the DCs through the formation of minimalist binary complexes, which exhibited great advantages of low carrier/gene ratios, high gene loading efficiency and well biocompatibility. The identified GA stimulated strong type I interferon (IFN) expression via the intracellular stimulator of interferon genes (STING) pathway and enhanced DC maturation and activation, which could potentially facilitate strong immunogenicity of DC vaccines. Importantly, DC maturation and activation could be further strengthened by co-delivering maturation stimuli with mRNA/GA complexes, and adoptive transfer of gene-engineered DC vaccines elicited strong T cell responses and thus inhibited tumor growth in vivo . The further studies indicated GAs can be formulated into lipid nanoparticle (LNP)-like quinary complexes that presented 6.9-fold higher mRNA delivery efficiency on the DCs than the commercial Lipofectamine 2000. These results suggest that GA-based molecular library is a powerful platform to develop versatile gene delivery vectors for immune cell engineering.
研究领域:
免疫学
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分子生物学
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药学
·
癌症研究
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高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2022
·
IF 4.46
Shaoxiong Chen,Zhanbing Sun,Weihua Deng,Guilan Li,Xiuli Liu,Zhaohui Zhang
Beryllium and its compounds can cause pulmonary interstitial fibrosis through mechanisms that are not yet clear. Long non-coding RNA (lncRNA) is implicated in various diseases. The molecular toxicity of beryllium sulfate (BeSO 4 ) was investigated through the RNA-seq analysis of the lncRNA and mRNA whole-transcriptome of BeSO 4 -treated 16HBE cells. A total of 1014 lncRNAs (535 upregulated and 479 downregulated) and 4035 mRNAs (2224 upregulated and 1811 downregulated) were found to be significantly dysregulated (|logFC| ≥> 2.0, p < 0.05) in the BeSO 4 -treated groups when compared with the control group. Five differentially expressed lncRNAs and mRNAs were verified by qRT-PCR. KEGG analysis showed that lncRNA regulates the ECM receiver interaction and PI3K/AKT signaling pathways, etc. In addition, H19:17, lnc-C5orf13–1:1, lnc-CRYAA-17:1, lnc-VSTM5–1:11, and lnc-THSD7A-7:1 may regulate BeSO 4 -induced 16HBE cytotoxicity through ceRNA mechanism. The results of this study will provide some theoretical support for the study of the toxic mechanism of beryllium and its compounds.
研究领域:
毒理学
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分子生物学
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基因组学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）