ORAL DISEASES
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2022
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IF 4.068
Deao Gu,Hanxiao Liu,Xinyi Qiu,Yijun Yu,Xuna Tang,Chao Liu,Leiying Miao
Objectives Human-derived pulp stem cells play key roles during dentinogenesis. Erythropoietin is reportedly involved in osteoblastogenesis and facilitates bone formation. However, the mechanism is still unknown. This research was to study the potential of erythropoietin in enhancing odontoblastic differentiation of human-derived pulp stem cells and to determine the underlying mechanism. Methods The human-derived pulp stem cells were treated with erythropoietin, EphB4 inhibitor, and MAPK inhibitors, and the odontoblastic differentiation was measured by ALP staining, ALP activity assay, alizarin red S staining, and their quantitative analysis, and RT-qPCR of DSPP, DMP1, OCN, and RUNX2. The direct pulp capping model was established to evaluate the formation of tertiary dentin after treatment with erythropoietin. Western blot assay was conducted to assess relevant protein expressions in the phosphorylated EphB4 and MAPK pathway. Results The results showed that erythropoietin promoted odontoblastic differentiation of human-derived pulp stem cells at 20 U/ml. Erythropoietin induced tertiary dentin formation in vivo. The potential mechanism of this was upregulating phosphorylated EphB4 and phosphorylated MAPK; furthermore, this effect could be decreased by EphB4 inhibitors, which inhibited MAPK phosphorylation. Blockage of MAPK pathways attenuated human-derived pulp stem cells’ odontoblastic differentiation, suggesting that MAPK pathways are involved. Conclusion Erythropoietin induced tertiary dentin formation in vivo. And erythropoietin enhanced human-derived pulp stem cells' odontoblastic differentiation via the EphB4-mediated MAPK signaling pathway.
研究领域:
牙科学
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干细胞研究
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2018
·Vol. 42
·期 5
·2373-2382
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IF 2.784
Hao Liu,Xue Li,Wen Qian Yu,Cai Xia Liu
Congenital diaphragmatic hernia (CDH) is a common congenital malformation associated with high mortality rates, mainly due to pulmonary hypoplasia and persistent pulmonary hypertension following birth. The present study aimed to investigate abnormal lung development in a rat CDH model, and examine temporal and spatial changes in the expression of ephrin type‑B receptor 4 (EPHB4) and ephrin‑B2 (EFNB2) during fetal lung development, to elucidate the role of these factors during lung morphogenesis. Pregnant rats received nitrofen on embryonic day (E) 8.5 to induce CDH, and fetal lungs were collected on E13.5, E15.5, E17.5, E19.5, and E21.5. The mean linear intercept (MLI) and mean alveolar number (MAN) were observed in fetal lung tissue at E21.5 following hematoxylin and eosin staining. E13.5 fetal lungs were cultured for 96 h in serum‑free medium and branch development was observed under a microscope. The gene and protein expression levels of EPHB4 and EFNB2 were assessed by reverse transcription‑quantitative polymerase chain reaction analysis, and immunoblotting and immunohistochemistry, respectively. The fetal rat lungs were treated with EFNB2 and the activity of key signaling pathways was assessed. The lung index (lung weight/body weight) at E21.5 was significantly lower in the CDH rats, compared with that in the control fetal rats. The MLI and MAN were also lower in the CDH group. The number of lung terminal buds at E13.5 (embryonic stage), and the lung‑explant perimeter and surface were all smaller in the CDH group rats than in the control group at the same age. Pulmonary hypoplasia was observed following 96 h of in vitro culture. No significant differences were found in the expression levels of EFNB2 and EPHB4 between the CDH and control groups at E13.5 (embryonic stage) or E15.5 (pseudoglandular stage), however, EFNB2 and EPHB4 were significantly upregulated at E17.5 (canalicular stage), and at E19.5 and E21.5 (saccular/alveolar stages). EFNB2 stimulated pulmonary branching and EFNB2 supplementation decreased the activity of p38, c‑Jun NH2‑terminal kinase, extracellular signal‑regulated kinase, and signal transducer and activator of transcription. The CDH fetal rats developed pulmonary dysplasia at an early stage of fetal pulmonary development. Upregulated expression of EFNB2 and EPHB4 was observed in the rat lung of nitrofen‑induced CDH, and the increased expression of EFNB2 promoted rat lung development in the nitrofen‑induced CDH model.
研究领域:
发育生物学
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分子生物学
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儿科
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DOI
PubMed
高影响因子
DRUG DELIVERY
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2026
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IF 8
Wanting Jiang,Hao Zheng,Shengmei Wang,Rubing Xu,Xi Chen,Jing Yang,Xinhua Xia
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, yet conventional chemotherapy is limited by poor tumor specificity and severe toxicity. Cantharidin (CTD), a natural antitumor agent, is hindered by nephrotoxicity and hepatotoxicity. This study aimed to construct a dual-ligand-modified CTD-loaded solid lipid nanoparticle (GA-FA-CSLNs) using 18-glycyrrhetinic acid (GA) for hepatocyte targeting and folate-PEG3500-DSPE (FA) for long circulation, and to evaluate its antitumor efficacy, mechanism, and safety. GA-FA-CSLNs were prepared by emulsification-ultrasonication and optimized via Box-Behnken design. The nanoparticles were characterized. In vitro antitumor activity was assessed in Huh-7 cells using CCK-8, flow cytometry, and Western blotting. In vivo efficacy and safety were evaluated in Huh-7 tumor-bearing nude mice, and pharmacokinetics in SD rats. GA-FA-CSLNs exhibited favorable physicochemical properties. In vitro studies showed enhanced cellular uptake, the lowest IC50, and 43.2% apoptosis in Huh-7 cells. Mechanistically, GA-FA-CSLNs downregulated Eph receptor B4(EphB4) and Bcl-2, while upregulating caspase-3 and Bax. In vivo, the tumor inhibition rate reached 58.67%, superior to free CTD and sorafenib, with 100% 14-day survival and no significant abnormalities in serum biochemistry or histopathology. Pharmacokinetic analysis showed prolonged elimination half-life (2.54 h) and a 3.2-fold increase in area under the blood concentration-time curve versus unmodified CSLNs. GA-FA-CSLNs represent a promising actively targeted nanoplatform that enhances CTD antitumor efficacy against HCC via EphB4 pathway inhibition while reducing systemic toxicity, offering a potential strategy for targeted HCC therapy.
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DOI
PubMed
高影响因子
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