Advanced Healthcare Materials
·
2022
·Vol. 11
·期 23
·2201615
·
IF 11.092
Geng Yang,Mengyue Li,Ting Song,Xiangyan Chen,Hanxi Zhang,Xiaodan Wei,Ningxi Li,Tingting Li,Xiang Qin,Shun Li,Fengming You,Chunhui Wu,Wei Zhang,Yiyao Liu,Hong Yang
The combination of photothermal therapy (PTT) and chemotherapy is considered a promising tumor treatment modality, nevertheless, cellular resistance induced by heat shock proteins (HSPs) overexpressed in tumor cells will restrict the therapeutic effect. Herein, a multifunctional nanobeacon DOX/HCuS@PDA-MB (D/CP-MB) with a scout function for HSP90 mRNA fluorescence detection and near-infrared (NIR) triggered drug release for sensitizing chemo–photothermal therapy, is proposed. In the theranostic nanobeacons, HSP90MBs not only enable fluorescence detection of intracellular HSP90 mRNAs, but also downregulate the expression of HSP90 to reduce cell resistance. With the assistance of NIR and guidance of fluorescence imaging, spatiotemporal doxorubicin release can be achieved by the trigger of the photothermal effect, allowing for combined chemotherapy and photothermal treatment. Furthermore, the dual photothermal effect of hollow mesoporous CuS (HCuS) and polydopamine will lead to a better photothermal effect. Moreover, compared with other control groups, D/CP-MB nanobeacons exhibit effective boost therapeutic efficacy by inducing significant suppression of tumor proliferation and enhancement of apoptosis both in vitro and in vivo. In summary, this work provides novel theranostic nanobeacons that integrate imaging and therapy in a single nanoparticle, this strategy of imaging-guided therapy can enable precise tumor treatment and effectively improve tumor treatment efficacy.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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分子生物学
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诊疗学
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yu Han,Kai Zhang,Ning Xin,Xintao Gao,Guohua Ma,Jingtong An,Yantao Li
Despite recent advancements in lipid nanoparticles (LNPs)-based messenger RNA (mRNA) delivery, significant challenges persist in the structural optimization and functional modulation of their components for cancer immunotherapy, particularly regarding inadequate organ-specific targeting, and insufficient immune activation. Notably, metal ions have demonstrated emerging immunomodulatory potential, yet their coordinated self-assembly within LNPs as adjuvants to enhance the immunotherapeutic efficacy remains largely unexplored. To address these limitations, we combine newly designed imidazole-based LNPs with functional metal ions (Zn 2+ ) to develop novel Zn-coordinated LNP-based mRNA vaccines. A total of 48 imidazole-based ionizable lipids were designed and synthesized, among which C2–13 LNPs emerged as the top-performing formulation in terms of transfection efficiency. By innovatively incorporating Zn 2+ into C2–13 LNPs via coordination interaction, we further developed the novel metal-coordinated mRNA delivery systems, referred to as Zn-C2–13 LNPs. Compared to their non-metal counterparts, Zn-C2–13 LNPs exhibited markedly improved transfection efficiency and antigen presentation in vitro . Impressively, the synergistic effect of the optimized LNP formulation and Zn 2+ in the Zn-C2–13/mOVA systems (Zn-C2–13 LNPs loading ovalbumin mRNA) resulted in superior spleen-selective expression and immune response, significantly boosting the efficacy of cancer immunotherapy in the B16F10 ovalbumin-expressing (B16F10-OVA) melanoma tumor model. Collectively, this novel metal-coordinated LNPs improve specific organ targeting and immune responses, presenting a promising strategy to advance mRNA vaccine-based cancer immunotherapy.
研究领域:
免疫学
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肿瘤学
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纳米医学
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分子生物学
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转化医学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Jingwen Shi,Wenda Jing,Yueyun He,Ying Huang
Despite decades of research, endometriosis remains a mysterious gynecological disease with unknown etiology and pathogenesis. Krüppel-like Factor 6 (KLF6), a transcription factor, has a wide expression profile and regulates a variety of biological processes. Here, we investigated the expression and function of KLF6 and its possible regulatory mechanisms in endometriosis. To determine the function of KLF6, knockdown and overexpression experiments were performed in eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (EC-ESCs), respectively. Cell viability, apoptosis, migration, invasion, and angiogenesis assays were conducted in ESCs. ChIP-sequencing and mRNA-sequencing were performed to investigate the functional mechanism of KLF6 in regulating ESCs. We found that KLF6 was highly expressed in eutopic endometrium of endometriosis patients, compared with ectopic endometrium. Similarly, the same was true in EU-ESCs, which was compared with EC-ESCs. Overexpression of KLF6 significantly suppressed EC-ESC proliferation, migration and invasion and induced cell apoptosis, while knockdown of KLF6 resulted in the opposite effects on EU-ESCs. Overexpression of KLF6 significantly inhibited EC-ESC angiogenesis. Mechanistically, the results of ChIP sequencing and mRNA sequencing revealed that CTNNB1 may be a transcriptional target regulated by KLF6. Reintroduction of KLF6 reversed the effects of KLF6 knockdown on EU-ESCs. KLF6 inhibited the proliferation, migration and angiogenesis of EC-ESCs by inhibiting the expression of CTNNB1. Our findings provided a new perspective on the role of KLF6 in endometriosis progression and inspire potential targeted therapeutic strategies.
研究领域:
妇科学
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分子生物学
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转录因子
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疾病发病机制
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产品关联
DOI
PubMed
高影响因子
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
·
2020
·
IF 2.074
AiJun Huang,LiPing Chen,YiMing Wang,ShuQiang Ma,Song Jin,Hanzhou Cai,Xingzhong Huang,Hongbo Zhang,ZengRong Wang,Kun Lin,Fangsiyu Lin
Background:5-fluorouracil (5-FU) is a widely used drug for cancer treatment, but its effect and underlying mechanisms on osteosarcoma (OS) cells remain unclear.Methods:U2OS and MG63 cells were treated with 0, 50, 100, and 500 μM 5-FU. MTS and flow cytometry were used to examine the effect of 5-FU on cell viability and apoptosis, respectively. Circular RNA (circRNA) expression was detected using RNA sequencing and quantitative real-time PCR (qPCR). Differentially expressed circRNAs were further subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to predict their functions. A circRNA–miRNA–mRNA interaction network was generated to analyze the regulatory networks of 5-FU–induced differentially expressed circRNAs. Western blotting (WB) was used to verify the protein in the downstream of circRNAs.Results:5-FU inhibited the cell viability of the MG63 cells in a concentration-dependent manner. The most significant effect was observed in the cells treated with 500 μM 5-FU. Apoptosis was also increased in the MG63 cells after 500 μM 5-FU treatment for 3 days. RNA sequencing results showed that 183 differentially expressed circRNAs (172 upregulated and 11 downregulated) in 5-FU–treated cells. KEGG and GO analysis showed that the differentially expressed circRNAs were primarily enriched in proliferation-, apoptosis-, and metabolism-related functions. qPCR was used to verify the most upregulated and downregulated circRNAs. The circRNA–miRNA–mRNA interaction network showed that these 8 circRNAs had a sizable regulatory network that links a series of genes involved in tumor suppression.Conclusion:5-FU treatment resulted in the differentially expressed circRNAs that were proliferation- and apoptosis-associated and were involved in the 5-FU–induced inhibition of tumor proliferation in OS cells.
研究领域:
肿瘤学
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分子生物学
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基因组学
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癌症治疗
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2024
·
IF 3.3
Liyuan Zhao,Lei Shi,Zixuan Yang,Minhui Zheng,Zhimin Sun,Luyao Sun,Mengyun Gu,Xin Song,Gang Liu,Feng Miao,Ming Wang,Shaoqiu Zheng,Peng Zhang,Naping Tang,Kelan Liu
Isoprenaline hydrochloride (IH) is a β-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague–Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.
研究领域:
心脏病学
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分子生物学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2018
·Vol. 9
·期 1
·1-15
·
IF 12.353
Usman Waqas Muhammad,Pham Tin Chanh,Kwok Yuk Yan,Vu Luyen Tien,Ma Victor,Peng Boya,Chan Yuen San,Wei Likun,Chin Siew Mei,Azad Ajijur,He Alex Bai-Liang,Leung Anskar Y. H.,Yang Mengsu,Shyh-Chang Ng,Cho William C.,Shi Jiahai,Le Minh T. N.
Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR–Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.
研究领域:
药理学
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分子生物学
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基因治疗
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生物技术
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产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Hong Jiang,Chen Zhang,Wen He
Background Dracocephalum heterophyllum Benth flavonoid (DHBF) is a Tibetan and Uighur traditional medicine used to treat various disorders such as hypertension, lung heat, cough, and bronchitis; it has good antioxidant activity. Previous studies have shown that DHBF can reduce blood pressure in renovascular hypertensive rats, improve left ventricular systolic and diastolic function, and improve myocardial contractility. Therefore, we aimed to study the effect of DHBF on cardiomyocyte hypertrophy in cultured cells. Material/Methods Neonatal rat cardiomyocytes were cultured, and hypertrophy was induced by angiotensin II (Ang II), with or without varying concentrations of the DHBF extract. Cell Counting Kit-8 assay was used to assess cell viability, RT-qPCR was used to determine mRNA levels, confocal laser scanning microscopy was used to measure cell surface area and intracellular Ca 2+ concentrations ([Ca 2+ ] i ), and colorimetric assays were used to assess nitric oxide (NO) levels and nitric oxide synthase (NOS) activity. Results Ang II treatment of cardiomyocytes reduced cell viability to ~75% that of controls. Ang II treatment also increased cell surface area; increased mRNA expression of c-jun, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC); increased [Ca 2+ ] i ; and reduced NOS activity and NO production. DHBF treatment could reverse these effects in a concentration-dependent manner. Conclusions These results showed that DHBF can ameliorate cardiomyocyte hypertrophy induced by Ang II, as indicated by the downregulation of cardiac hypertrophy genes ( ANP , BNP , and β -MHC ) and reduction in cell surface area. The mechanism may be related to NO release and [Ca 2+ ] I regulation.
研究领域:
心脏病学
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药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Jing Cong,Mubai Li,Yu Wang,Hongli Ma,Xinming Yang,Jingshu Gao,Long Wang,Xiaoke Wu
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women at reproductive age. The therapeutic effect of electroacupuncture (EA) on PCOS has been revealed, while the anti-PCOS mechanisms of EA have not been fully explored. In this study, PCOS were induced in rats by daily injection with dehydroepiandrosterone (DHEA) for 20 days and EA treatment was performed for 5 weeks. The mRNA expression profiles in ovarian tissues from control, PCOS, and EA-treated rats were examined by high-throughput mRNA sequencing. 5'-aminolevulinate synthase 2 (Alas2), a vital rate-limiting enzyme of the heme synthesis pathway, was selected to be further studied. PCOS led to the upregulation of Alas2 mRNA, whereas EA treatment restored this change. In vitro, primary ovarian granulosa cells (GCs) were challenged with H 2 O 2 to mimic the oxidative stress (OS) state in PCOS. H 2 O 2 induced apoptosis, OS, mitochondrial dysfunction, as well as Alas2 overexpression in GCs, while lentivirus-mediated Alas2 knockdown evidently restrained the above impairments. In summary, this study highlights the crucial role of Alas2 in cell apoptosis, OS, and mitochondrial dysfunction of PCOS GCs and provides potential therapeutic candidates for further investigation on PCOS treatment.
研究领域:
生殖医学
·
内分泌学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Wenyi Wang,Junli Chang,Hongfeng Ruan,Xingyuan Sun,Fulai Zhao,Peng Zhao,Chujie Zhou,Junjie Tong,Suxia Guo,Qi Shi,Yongjun Wang,Weian Zhang,Yanping Yang
Cancer is a global leading cause of death, with nearly 10 million people dying from cancer in 2020. Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, the potential molecular mechanisms remain obscure. Herein, we designed a near-infrared (NIR) light-activated nanoplatform (TPBC-PEG) to explore the therapeutic effects and mechanisms of PDT by using a model of intratibial primary and pulmonary metastasis osteosarcoma. Under laser irradiation, TPBC-PEG photosensitizer dose-dependently inhibited proliferative and metastatic capabilities while promoting apoptosis of osteosarcoma cells in vitro, and also effectively suppressed carcinogenesis and pulmonary metastasis in osteosarcoma xenograft mouse model. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis after high-throughput mRNA-seq indicated that the HIPPO signaling pathway was one of the 20 most significantly related signaling pathways. And a series of experiments for determining the HIPPO signaling activity were conducted to reconfirm the specificity. Collectively, PDT of TPBC-PEG micelles against carcinogenesis and pulmonary metastasis of deep-seated intratibial osteosarcoma was achieved by activating HIPPO signaling pathway. Our study identified a hitherto uncharacterized molecular mechanism of PDT, which may provide new insights to understand and design promising nanoplatforms for future cancer therapies.
研究领域:
肿瘤学
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分子生物学
·
治疗学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
PEDIATRIC RESEARCH
·
2023
·
IF 3.6
Wang Qi,Shi Xulai,Li Ping-Ping,Gao Li,Zhou Yueyuan,Li Luyao,Ye Hao,Fu Xiaoqin,Li Peijun
Background Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. Methods miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride–pilocarpine. Results We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls ( p < 0.01), of which miR-27a-3p exhibited a very low p value ( p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased ( p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. Conclusions MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. Impact
A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children.
Plasma miR-27a-3p was one of the miRNAs with a low p value.
GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p.
miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.
研究领域:
神经科学
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分子生物学
·
儿科
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生物标志物研究
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 5
·3715-3722
·
IF 1.448
Haiming Yu,Yuefei Wang,Xiaoqing Wang,Junjie Guo,Hui Wang,Hao Zhang,Fengxia Du
Bacterial resistance to antimicrobial agents, including multidrug resistance, is an increasing problem in the treatment of infectious diseases. The development of resistance‑modifying agents represents a potential strategy to alleviate the spread of bacterial resistance to antibiotics. A checkerboard microdilution assay was used to determine the synergy of jatrorrhizine and the antibiotic, norfloxacin (NFX). A bacterial ethidium bromide efflux assay, reverse transcription semi‑quantitative polymerase chain reaction analysis and molecular docking study were performed. The three‑dimensional structure of NorA multidrug efflux pump (NorA) was generated using a multiple threading approach. A murine thigh infection model was used to evaluate the in vivo synergistic effect. As a natural product, jatrorrhizine exhibited little antibacterial activity against methicillin‑resistant Staphylococcus aureus (MRSA) SA1199B with a minimum inhibitory concentration (MIC) of 64 mg/l. According to the investigations of the mechanism, jatrorrhizine significantly inhibited bacterial drug efflux and the expression of NorA in the mRNA level as it can bind to NorA by hydrogen‑bonds, hydrophobic and electrostatic interactions. The in vivo synergistical bactericidal activity of jatrorrhizine and NFX against MRSA was confirmed in a murine thigh infection model. As a novel resistance‑modifying agent, jatrorrhizine exhibited in vitro and in vivo synergistic activities against MRSA, and inhibited bacterial drug efflux. The effects were mediated by the suppression of NorA mRNA expression and/or interactions with NorA efflux pump. These data support the hypothesis that jatrorrhizine is a potential agent for therapeutic use in infections caused by MRSA.
研究领域:
微生物学
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药理学
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传染病学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Xiaoting Liu,Xiaowen Xu,Yi Zhou,Nan Zhang,Wei Jiang
Overexpression of adenosine 5′-triphosphate-binding cassette transporters is one of the primary causes of drug resistance in cancer. Downregulating the expression of these transporters by inhibiting the mRNA translation process is an effective approach to cope up with this situation. Herein, multifunctional molecular beacons (MBs)-modified gold nanoparticle (AuNP) as a nanocarrier (MBs-AuNP) is developed for synergistic inhibition and in situ imaging of drug-resistant-related mRNAs in living cells. MBs-AuNP is composed of (i) triple specially designed molecular beacons modified on the surface of AuNP, for binding drug-resistant-related mRNAs, loading doxorubicin (Dox), and reporting the fluorescence signal, and (ii) AuNP, for loading MBs, introducing them into cells, and quenching their fluorescence. After uptake by cells, MBs-AuNP will hybridize with three different drug-resistant-related mRNAs (MDR1 mRNA, MRP1 mRNA, and BCRP mRNA), respectively, which could inhibit their translation to decrease efflux protein expression and lead to AuNP-quenched fluorescence recovery for in situ imaging. Real-time quantitative-polymerase chain reaction and western blot results showed that drug-resistant-related mRNAs and efflux proteins expression both decreased. Dox-loaded MBs-AuNP exhibited higher suppression efficacy compared to that of free Dox against HepG2/ADR (0.35 vs 1.06 μM of IC50) and MCF-7/ADR (2.78 vs >5 μM of IC50). Direct observation of intracellular hybridization events and differentiation of drug-resistant cancer cells or non-drug-resistant cancer cells could be accomplished through fluorescence imaging analysis. This nanocarrier is capable of downregulating the expression of multiple efflux proteins by gene silencing, allows in situ monitoring of silencing events, and thus provides a powerful strategy to cope up with drug resistance at the gene level.
研究领域:
纳米技术
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癌症生物学
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分子生物学
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药学
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生物医学工程
✓ 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）