摘要
Objective:To investigate the protective mechanism of TRPV4 channel inhibitor on blood-brain barrier(BBB)damage after traumatic brain injury(TBI).Methods:The TBI rat model was established.TRPV4 channel inhibitor HC067047 or PKC-δ inhibitor Rottlerin was used to detect changes in BBB permeability,neurological function score,and the expression of microvascular endothelial tight junction proteins ZO-1 and ZO-2 in brain injury areas after TBI.Results:Compared with the Sham group,BBB permeability significantly increased,brain neurological function score significantly decreased,and the expression of ZO-1 and ZO-2 significantly decreased in TBI group(P＜0.05).Compared with the TBI group,after administration of HC067047 or Rottlerin,changes in BBB permeability,brain neurological function score,the expression of ZO-1 and ZO-2 were partially reversed(P＜0.05).Conclusions:TBI-induced BBB injury may be mediated by TRPV4 channel regulating PKC-δ signaling pathway to affect the expression of tight junction proteins ZO-1 and ZO-2.Inhibition of TRPV4 channel function or PKC-δ signal molecule can partially alleviate BBB damage induced by TBI.This study may provide new ideas for the treatment of clinical TBI.
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BACKGROUND:Growth differentiation factor 5 is a member of the transforming growth factor superfamily and one of the earliest markers of joint development.Growth differentiation factor 5 has an important role in cartilage repair. OBJECTIVE:To explore the action mechanism of growth differentiation factor 5-induced chondrogenic differentiation of bone marrow mesenchymal stem cells. METHODS:Rabbit bone marrow mesenchymal stem cells were isolated and cultured.CCK-8 assay was used to detect the effect of different mass concentrations of growth differentiation factor 5 on the proliferation activity of bone marrow mesenchymal stem cells.RT-PCR was utilized to detect the expression of genes related to chondrogenic differentiation of bone marrow mesenchymal stem cells induced by different mass concentrations of growth differentiation factor 5.To further investigate the action mechanism of growth differentiation factor 5-induced chondrogenic differentiation of bone marrow mesenchymal stem cells,we added inhibitor XAV-939 and activator Laduviglusib of Wnt/β-catenin signaling pathways to induce cell culture for 14 days.RT-PCR and western blot assay were performed to detect the expression of cartilage-related genes and Wnt/β-catenin signaling pathway proteins. RESULTS AND CONCLUSION:(1)CCK-8 results showed no significant effect of growth differentiation factor 5 on the proliferation of bone marrow mesenchymal stem cells.(2)Growth differentiation factor 5 promoted the expression of cartilage-related genes type Ⅱ collagen,aggrecan and Sox9,among which growth differentiation factor 5 induced a significant upregulation of cartilage-related genes in the 50 ng/mL group.(3)Addition of Laduviglusib,an activator of Wnt/β-catenin signaling pathway,upregulated Sox9,β-catenin and type Ⅱ collagen expression(P<0.05).Addition of XAV939,an inhibitor of Wnt/β-catenin signaling pathway,down-regulated Sox9,β-catenin and type Ⅱ collagen expression(P<0.05).(4)Taken together,growth differentiation factor 5-induced chondrogenic differentiation of bone marrow mesenchymal stem cells may be associated with the activation of the Wnt/β-catenin signaling pathway.
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[This corrects the article DOI: 10.1016/j.apsb.2021.04.022.].
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Insurmountable blood‒brain barrier (BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease (AD). Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing A
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Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor.