SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Qin Ma,Yilong Tu,Wen Yun,Mingming Zhang
A self-driven and self-catalytic (SDSC) tripedal DNA nanomachine was developed for microRNA-21 (miR-21) detection. The microRNA could open one arm of tripedal DNA nanomachine to form DNAzyme with a nearby arm through the proximity effect. After DNAzyme’s cleavage, the exposed DNA arm region competed with the third arm and produced a DNA segment (sequence Q). The released sequence Q initiated the next SDSC cycle of tripedal DNA nanomachine. In the special DNA nanomachines design, the components with close spatial localization were constructed on a single nanostructure, which significantly increased local reactant concentrations and reaction rates. A dynamic correlation was obtained from 10 pM to 50 nM between fluorescence signal and miR-21 concentration. The effective concentration of reactant greatly increased, compared with the free diffusible reactants. Consequently, the incubation time was significantly shorted to 35 min. This strategy showed a promising potential in miRNA detection and disease diagnosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Pulmonary Medicine
·
2024
·Vol. 24
·期 1
·1-16
·
IF 2.6
Sun Lili,Liu Lihua,Liang Dongxue,Liu Linlin
Pulmonary hypertension (PH) is a chronic pulmonary vascular disease and causes massive deaths. Here, we intended to investigate the function and mechanism of SOCS5 in PH. We engineered a hypoxia-induced PH model in mice. HE staining were implemented to evaluate pathological alterations in the lung tissues. The potential mechanism of SOCS5 in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was explored in vitro. RT-qPCR and western blot revealed that the level of SOCS5 was decreased both in PH mice and hypoxia-induced HPASMCs. Functional assays were performed for confirming the role of SOCS5 in modulating the cell phenotype and JAK2/STAT3 pathway in HPASMCs. Results revealed that overexpression of SOCS5 suppressed proliferation, migration and contraction of HPASMCs and negatively regulated the JAK2/STAT3 signaling pathway in HPASMCs under hypoxia in vitro, while knockdown of SOCS5 accelerated it. As evidenced by mechanism studies, SOCS5 was targeted and regulated by miR-155-5p, hence affecting on HPASMC proliferation, migration and contraction. These outcomes indicated that the decreased level of SOCS5 in hypoxia-induced HPASMCs promoted the cell proliferation, cell migration, and cell contraction through activating JAK2/STAT3 signaling pathway. Moreover, SOCS5 was targeted by miR-155-5p. All in all, our work hinted that miR-155-5p/SOCS5/JAK2/STAT3 axis played a crucial part in PH.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Ying Wen,Zhen Zou,Yitong Li,Danhua Zhang,Ziru Liu,Hong Liu,Xiejia Li,Wei Wu,Liyun Zeng,Qiongyan Zou,Wenjun Yi
The combination of photodynamic therapy (PDT) and gene therapy is a viable therapeutic approach for the management of secondary hyperparathyroidism (SHPT). Nevertheless, the effective delivery of photosensitizers or nucleotide drugs remains a crucial limitation in achieving therapeutic efficacy. MiR-146b-3p directly targeted BCL2, and its overexpression enhanced the antiproliferative, proautophagic, and proapoptotic effects during 5-aminolevulinic acid (5-ALA)-mediated PDT in this study. Herein, we investigated the potential of codelivering 5-ALA and miR-146b-3p to SHPT primary cells via polyamidoamine (PAMAM) and achieving enhanced therapeutic efficacy relative to that of monotreatment. The fabrication of the PAMAM-based 5-ALA and miR-146b-3p dual-delivery system (5-ALA@PAMAM/miR) involved the use of covalent condensation reactions and electrostatic self-assembly. The nanoparticles were characterized by various analytical techniques, including transmission electron microscopy (TEM), zeta potential measurements, and size measurements. Fluorescence and confocal laser scanning microscopy demonstrated a greater degree of cellular uptake of nanoparticles. Moreover, the synthesized nanoparticles considerably enhanced the effectiveness of PDT without systemic toxicity both in vitro and in vivo. Overall, the nanocarrier-gene-photosensitizer coloaded system is a promising platform for the efficient simultaneous delivery of miR-146b-3p and 5-ALA and achieves synergistic therapeutic effects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Junling An,Hao Li,Wenjing Wen,Gaojian Liu,Zixuan Huang,Xinwei Zhao,Gaofeng Liang
Liver cancer, particularly hepatocellular carcinoma (HCC), presents significant therapeutic challenges due to factors such as drug resistance and systemic toxicity. Ferroptosis, an iron-dependent form of cell death, offers a promising alternative to overcome these challenges. This study investigates the use of folic acid-modified iron oxide nanoparticles as a delivery system for miR-214-3p to promote ferroptosis in liver cancer cells. The folic acid modification enhances the efficiency of nanoparticle-mediated miR-214-3p delivery, thereby improving its therapeutic potential. miR-214-3p plays a dual role in promoting ferroptosis: first, by downregulating lipocalin-2 (LCN2), it acts synergistically with iron oxide nanoparticles to increase intracellular iron levels, reduce iron excretion, and promotes the Fenton reaction; second, by inhibiting glutathione peroxidase 4 (GPX4), it weakens cellular antioxidant defenses, further promoting ferroptosis. Our in vitro experiments demonstrated that the folic acid-modified nanoparticles effectively delivered miR-214-3p, resulting in significant ferroptosis in liver cancer cells. Animal models showed that FeNP/miR could effectively target tumors and had excellent tumor suppressive effects. This research highlights a promising approach for targeting HCC through enhanced nanoparticle-based gene therapy, offering a potential strategy in cancer treatment.
✓ 已验证
产品关联
DOI
高影响因子
SHOCK
·
2023
·Vol. 60
·期 5
·713
·
IF 3.1
Zhao Jinghong,Hu Jilin,Zhang Rongyi,Deng Jianping
Hypertension seems to inevitably cause cardiac remodeling, increasing the mortality of patients. This study aimed to explore the molecular mechanism of CCAAT/enhancer-binding protein delta (CEBPD)–mediated oxidative stress and inflammation in hypertensive cardiac remodeling. The hypertensive murine model was established through angiotensin-II injection, and hypertensive mice underwent overexpressed CEBPD vector injection, cardiac function evaluation, and observation of histological changes. The cell model was established by angiotensin-II treatment and transfected with overexpressed CEBPD vector. Cell viability and surface area and oxidative stress (reactive oxygen species/superoxide dismutase/lactate dehydrogenase/malondialdehyde) were assessed, and inflammatory factors (TNF-α/IL-1β/IL-6/IL-10) were determined both in vivo and in vitro . The levels of CEBPD, miR-96-5p, inositol 1,4,5-trisphosphate receptor 1 (IP3R), natriuretic peptide B, and natriuretic peptide A, collagen I, and collagen III in tissues and cells were determined. The binding relationships of CEBPD/miR-96-5p/IP3R 3′ untranslated region were validated. CEBPD was reduced in cardiac tissue of hypertensive mice, and CEBPD upregulation improved cardiac function and attenuated fibrosis and hypertrophy, along with reductions of reactive oxygen species/lactate dehydrogenase/malondialdehyde/TNF-α/IL-1β/IL-6 and increases in superoxide dismutase/IL-10. CEBPD enriched on the miR-96-5p promoter to promote miR-96-5p expression, whereas CEBPD and miR-96-5p negatively regulated IP3R. miR-96-5p silencing/IP3R overexpression reversed the alleviative role of CEBPD overexpression in hypertensive mice. In summary, CEBPD promoted miR-96-5p to negatively regulate IP3R expression to inhibit oxidative stress and inflammation, thereby alleviating hypertensive cardiac remodeling.
研究领域:
心脏病学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Hong Yu,Muyan Kong,Jinyi Chen,Jiyao Liu,Keyao Shan,Guiyu Zhang,Ruidi Jiang,Yinli Zheng,Qiulu Chen,Rong Zhang,Zhongqiu Liu,Jinjun Wu
Colorectal cancer (CRC), one of the primary causes of gastrointestinal malignancy-related mortality worldwide, encounters significant therapeutic challenges due to multidrug resistance. Multidrug resistance-associated protein 2 (MRP2), encoded by ABCC2, plays a crucial role in the development of drug resistance during clinical CRC treatment. This study elucidates a novel mechanism by which formononetin (FMNT), a bioactive isoflavone commonly found in food and medicinal-related plants, suppresses CRC via microRNA-490-3p (miR-490-3p)-mediated regulation of ABCC2 and synergizes with 5-fluorouracil (5-FU). HCT116 and SW480 cell lines as well as AOM/DSS-induced CRC models in wild-type and Mrp2 -/- mice were employed. The results demonstrated that FMNT markedly suppresses CRC proliferation in vitro and tumorigenesis in vivo . Transcriptomic profiling identified ABCC2 as the top target associated with FMNT’s efficacy. This finding was validated in clinical specimens, which revealed significant upregulation of MRP2 in human CRC tissues. FMNT markedly downregulated the MRP2 expression. Genetic ablation experiments further confirmed enhanced FMNT sensitivity in Mrp2 -/- mice and MRP2 silencing CRC cells. Mechanistically, FMNT upregulated tumor-suppressive miR-490-3p, which directly targets the ABCC2 3′UTR, thereby establishing a regulatory axis corroborated by gain/loss-of-function experiments. Notably, overexpression of miR-490-3p augmented FMNT’s antitumor effects, whereas inhibition of miR-490-3p diminished its efficacy. Therapeutic combination index analysis indicated robust synergy between FMNT and 5-FU, with combination therapy achieving superior tumor growth inhibition compared to monotherapies. Collectively, our findings uncover a novel miR-490-3p/ABCC2 regulatory mechanism underlying FMNT’s antitumor activity and highlight its potential for chemosensitization through ABCC2 inhibition, providing a strong rationale for flavonoid-based adjuvant therapy in CRC management.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
癌症研究
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2019
·Vol. 38
·期 1
·1-12
·
IF 5.646
Shi Weidong,Zhang Chenyue,Ning Zhouyu,Hua Yongqiang,Li Ye,Chen Lianyu,Liu Luming,Chen Zhen,Meng Zhiqiang
Background Long non-coding RNA LINC00346 has been recently suggested as a prognostic marker in pancreatic cancer. However, its biological function in pancreatic cancer has not yet been determined. In this study, we attempted to ascertain the role of LINC00346 in regulating the aggressiveness of pancreatic cancer.Methods The effects of overexpression and knockdown of LINC00346 on the proliferation, cell cycle progression, apoptosis, and gemcitabine resistance were investigated. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation assay were performed to search for potential microRNAs (miRs) that can interact with LINC00346.Results Overexpression of LINC00346 significantly enhanced the proliferation, colony formation, and tumorigenesis of pancreatic cancer cells. Conversely, knockdown of LINC00346 suppressed pancreatic cancer cell proliferation and caused a cell-cycle arrest at the G2/M-phase. Depletion of LINC00346 also enhanced gemcitabine sensitivity in pancreatic cancer cells both in vitro and in vivo. Mechanistic investigation revealed that LINC00346 acted as a sponge for miR-188-3p and blocked the repression of BRD4 by miR-188-3p in pancreatic cancer cells. Clinical evidence indicated a negative correlation between LINC00346 and miR-188-3p in pancreatic cancer specimens. Rescue experiments showed that LINC00346 attenuated the growth-suppressing and chemosensitizing effects of miR-188-3p on pancreatic cancer cells. In addition, silencing of BRD4 significantly inhibited LINC00346-induced pancreatic cancer cell proliferation and colony formation.Conclusion sLINC00346 shows the ability to promote pancreatic cancer growth and gemcitabine resistance, which is in part mediated by antagonization of miR-188-3p and induction of BRD4. Targeting LINC00346 may improve gemcitabine-based therapeutic efficacy.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
✓ 已验证
DOI
PubMed
高影响因子
BIOMARKERS
·
2026
·
IF 1.9
Yang Jiang,Xiaosheng Jin
Background PM2.5-induced COPD lacks effective therapies due to unclear pathogenesis. This study explores the role of miR-122 and PTEN in PM2.5-related COPD.Methods Using a combination of in vitro and in vivo assays, including cigarette smoke extract (CSE)-induced NR8383 cells and a rat smoke model, combined with MTT, qPCR, flow cytometry, WB, HE staining, Masson staining, HIC, and TUNEL assays, we investigated the role of microRNA-122 (miR-122) and phosphatase and tensin homolog (PTEN) in the molecular mechanisms underlying PM2.5-induced COPD.Results Our findings demonstrate that CSE-induced the down-regulated expression of miR-122 leads to the activation of PTEN, which in turn regulates the AKT signaling pathway in NR8383 cells. This modulation results in decreased expression of B-cell lymphoma 2 (BCL2), promoting cell apoptosis. Besides, the result from a rat model of COPD exposed to smoke also confirms this molecular axis which ultimately exacerbating COPD. Specifically, compared with the control, there is significant pulmonary structural damage in model rats exposed to PM2.5, including enlarged alveolar intervals, increased alveolar cavity size, pulmonary fibrosis, and evidence of alveolar destruction with concomitant parabronchial inflammation.Conclusion Our research reveals novel insights of PM2.5-induced COPD and proposes the miR-122/PTEN pathway as a potential therapeutic target.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2026
·
IF 3.5
Li Yuejin,Ouyang Yiming,Zhu Yu,Hou Dezhi,Li Xing,Guo Xiaodong,Sheng Ping,Wu Hailong,Liao Yingzhong,Gong Kunmei,Li Linhai
Natural killer (NK) cells play a crucial role in combating gastric cancer (GC). However, they undergo ferroptosis in the tumor microenvironment of GC, which weakens their antitumor effects. Exosomal circRNA influences GC progression. Previous studies have reported the cancer-promoting role of circPDSS1 in GC, but whether it is involved in NK cell ferroptosis remains unclear. This study aimed to investigate the role of GC cell-derived exosomal circPDSS1 in NK cell ferroptosis. A noncontact coculture system of GC cells (HGC-27, AGS, and MKN-45 cells) and human NK-92 cells was established, and humanized mouse and cell-derived xenograft (CDX) tumor models were constructed for joint investigation. Cell death and viability were assessed via flow cytometry, LDH release assays and CCK-8 assays; circPDSS1 stability was determined by agarose gel electrophoresis and actinomycin D treatment; ferroptosis was determined by measuring lipid ROS, MDA, and Fe 2+ levels; and key molecular interactions were determined by performing dual-luciferase reporter assays and RIP and RNA pull-down experiments. CD56 and CD16 expression was reduced in clinical tumor tissues. In vitro experiments revealed that the proportion of 7-AAD + NK-92 cells cocultured with GC cells was significantly increased, accompanied by increased cell mortality and decreased IFN-γ and TNF-α secretion. Further studies revealed that circPDSS1 expression was abnormally elevated in GC tissues and cells and was particularly enriched in MKN-45 cell-derived exosomes (Exos). Knockdown of circPDSS1 alleviated MKN-45-Exo-induced cell damage; reduced lipid ROS, MDA, and Fe 2+ levels in NK-92 cells; and delayed tumor progression. Furthermore, a ferroptosis inhibitor suppressed circPDSS1 overexpression-induced cell death. Mechanistically, circPDSS1 sponged miR-142-3p to upregulate ACSL4 expression, promoting NK cell ferroptosis. Exosomal circPDSS1 derived from GC cells contributes to NK cell ferroptosis by sponging miR-142-3p to increase ACSL4 expression and exacerbate GC.
✓ 已验证
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2026
·
IF 7.8
Li Xiao-huan,Lian Fu-wei,Lv Feng,Luo Xiao-Ling,Hu Bang-li,Zhang Li-tu,Ning Shu-fang
Background Mesenchymal stem cells (MSCs)-derived exosomes present great potential as nanocarriers for targeted drug delivery. Moreover, the therapeutic efficacy of exosomes can be substantially enhanced through functional modifications and the incorporation of bioactive molecules. Methods In this study, the MSCs were cultured under two-dimensional (2D) and three-dimensional (3D) cell culture conditions. The culture supernatants were collected for isolating exosomes. The characteristics and yields of exosomes from 2D and 3D cultures were detected by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), western blot analysis, and bicinchoninic acid (BCA) assay. Subsequently, 3D exosomes were loaded with miR-99b-5p and modified with iRGD peptide were formed into a new engineered exosome, designated as iRGD-Exo-miR-99b-5p. The effects of these engineered exosomes on the progression of colorectal cancer (CRC) were assessed through a series of in vivo and in vitro experiments. Results The 3D-cultured MSCs exhibited a higher yield of exosomes and enhanced uptake by CRC cells. Further in vitro experiments demonstrated that 3D-exosomes loaded with miR-99b-5p effectively inhibit the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells. Results from a xenograft tumor model indicate that iRGD-modified exosomes were significantly enriched at tumor sites. Furthermore, exosomes modified with iRGD and loaded with miR-99b-5p were employed for CRC treatment, resulting in substantial tumor growth inhibition and enhanced the chemotherapy efficacy of 5-fluorouracil (5-FU) in vivo, without inducing notable toxicity or side effects. Mechanistically, exosome-mediated delivery of miR-99b-5p downregulated FGFR3 expression, thereby inhibiting the activation of the PI3K/AKt signaling pathway and promoting ferroptosis, ultimately attenuating CRC progression. Conclusions Collectively, iRGD-modified 3D exosomes loaded with miR-99b-5p were able to specifically target tumor sites, thereby significantly suppressing CRC growth through the induction of ferroptosis via regulating the FGFR3/PI3K/AKt signaling pathway. These findings suggest that functional engineering and bioactive loading of 3D-exosomes derived from MSCs represent a promising strategy for targeted cancer therapy. Graphical
✓ 已验证
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Wenjia Guo,Haifeng Huang,Hong Wang,Xiaodan Tan,Yujun Tu,Chao Gu,Pu Xiang,Lin Chen,Zhe Peng,Yang Yang,Dongzhi Ran,Yin Luo,Junqing Yang
The objective of this study was to explore the effects and underlying mechanisms of miR-690 on hepatic steatosis in db/db mice. Our findings revealed that miR-690 was downregulated in the liver of db/db mice and high-glucose (HG)-treated NCTC1469 cells. In vivo, miR-690 overexpression alleviated hyperglycemia, hyperlipidemia, and hyperinsulinemia, improved liver function, and mitigated steatosis and pathological damage. In vitro , miR-690 enhanced cell viability and glucose uptake while reducing lipid deposition. Mechanistically, bioinformatics analysis identified 15-LOX and NF-KappaB P65 as potential miR-690 targets, with their expression levels inversely correlated with miR-690. Furthermore, treatment with miR-690 agomir downregulated 15-LOX and NF-KappaB P65, although dual-luciferase reporter assays confirmed that 15-LOX is indirectly targeted by miR-690. Additionally, miR-690 agomir increased LC3BII/I and Beclin1 levels while decreased P62 and p-mTOR (Ser2448)/mTOR and induced autophagosome formation. Moreover, overexpression of 15-LOX or NF-KappaB P65 reversed the protective effects of miR-690 on autophagy. Collectively, these results suggest that miR-690 exerts hepatoprotective effects against diabetic hepatic steatosis by activating autophagy via modulating 15-LOX and NF-KappaB P65, providing experimental evidence for its potential use in the treatment of hepatic steatosis in diabetes, and new insight into diabetes drug development for targeting miR-690.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Stem Cells
·
2021
·
IF 2.5
Qiong Li,Lei Huang
Background and Objectives MiR-148a-3p has been reported to regulate the differentiation of marrow stromal cell osteoblast. In this study, whether miR-148a-3p regulated the odontoblastic differentiation of human dental pulp stem cells (hDPSCs) or not was explored. Methods and Results The hDPSCs were isolated and identified via flow cytometry. Targets of miR-148a-3p were identified via bioinformatics and dual-luciferase reporter assay. After the cell was cultured in the odontogenic differentiation medium or infected, cell viability, invasion, and odontoblastic differentiation were detected via MTT, transwell, and Alizarin Red S staining, respectively. The miR-148a-3p, Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions were determined by RT-qPCR and Western blot. The hDPSCs odontoblastic differentiation downregulated the miR-148a-3p expression and upregulated Wnt1 expression. Wnt1 was determined as the target for miR-148a-3p. MiR-148a-3p mimic and siWnt1 suppressed the cell viability, invasion, and odontoblastic differentiation of hDPSCs and inhibited the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. In contrast, miR-148a-3p inhibitor and overexpressed Wnt1 promoted the cell viability, invasion, and odontoblastic differentiation of hDPSCs, and upregulated the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. Also, miR-148a-3p mimic and inhibitor reversed the effects of Wnt1 overexpression and siWnt1. Conclusions MiR-148a-3p modulated the invasion and odontoblastic differentiation of hDPSCs through the Wnt1/β-catenin pathway.
研究领域:
牙科研究
·
干细胞生物学
·
分子生物学
·
细胞分化
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）