scholarly journals Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Xing Li ◽  
Dan Luo ◽  
Yu Hou ◽  
Yonghui Hou ◽  
Shudong Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Endothelial Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Tanshinone Iia ◽  
Protective Effects ◽  
Cord Injury

Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.

Adipose mesenchymal stem cell transplantation alleviates spinal cord injury-induced neuroinflammation partly by suppressing the Jagged1/Notch pathway

2019 ◽  
Author(s):  
Zhou Zhilai ◽  
Tian Xiaobo ◽  
Mo Biling ◽  
Xu Huali ◽  
Yao Shun ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Therapeutic Effects ◽  
Mesenchymal Stem Cell Transplantation ◽  
Cord Injury

Abstract Background The therapeutic effects of adipose-derived mesenchymal stem cell (ADSC) transplantation have been demonstrated in several models of central nervous system (CNS) injury and are thought to involve the modulation of the inflammatory response. However, the exact underlying molecular mechanism is poorly understood. Activation of the Jagged1/Notch signaling pathway is thought to involve inflammatory and gliotic events in the CNS. Here, we elucidated the effect of ADSC transplantation on the inflammatory reaction after spinal cord injury (SCI) and the potential mechanism mediated by Jagged1/Notch signaling pathway suppression.Methods Using a mouse model of compression SCI, ADSCs and Jagged1 small interfering RNA (siRNA) were injected into the spinal cord. Locomotor function, spinal cord tissue morphology and the levels of various proteins and transcripts were compared between groups.Results ADSC treatment resulted in significant downregulation of proinflammatory mediator expression and reduced ionized calcium binding adapter molecule 1 (Iba1) and ED1 staining in the injured spinal cord, promoting the survival of neurons. These changes were accompanied by improved functional recovery. The augmentation of the Jagged1/Notch signaling pathway after SCI was suppressed by ADSC transplantation. The inhibition of the Jagged1/Notch signaling pathway by Jagged1 siRNA resulted in a decrease in SCI-induced proinflammatory cytokines as well as the activation of microglia. Furthermore, Jagged1 knockdown suppressed the phosphorylation of JAK/STAT3 following SCI.Conclusion The results of this study demonstrated that the therapeutic effects of ADSCs in SCI mice were partly due to Jagged1/notch signaling pathway inhibition and a subsequent reduction in JAK/STAT3 phosphorylation.

Treatment of Intrauterine Adhesions with Human Amnion Mesenchymal Stromal Cells (hAMSCs) on Promoting Endometrial Regeneration and Repair Via Notch Signaling Pathway Regulation

2020 ◽  
Author(s):  
Jie Yu ◽  
Wenwen Zhang ◽  
Jiayue Huang ◽  
Yating Gou ◽  
Congcong Sun ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Intrauterine Adhesions ◽  
Epithelial Markers ◽  
Qrt Pcr ◽  
Endometrial Epithelial Cells

Abstract Background: Human amniotic mesenchymal stem cells(hAMSCs) can repair and improve the damaged endometrium which its aplastic disorder is the main reason for intrauterine adhesions(IUAs).Methods: We conducted in vivo and in vitro experiments. In vivo experiments: 45 female Sprague-Dawley(SD) rats were involved and randomized equally into Sham group, IUA group, Estradiol(E2) group, hAMSCs group, and E2 + hAMSCs group. The effect of hAMSCs and E2 only or combined was evaluated by Hematoxylin-eosin(HE) and Masson staining. The expression of epithelial markers and key proteins of Notch signaling pathway by Immunohistochemistry. In vitro experiments: Firstly, the hAMSCs cells were taken and divided into control group and induced group in which hAMSCs were differentiated into endometrial epithelial cells in induced microenvironment, and extracted their RNA respectively. The expression of epithelial markers and Notch1 messenger RNA (mRNA) was detected by Real-time quantitative polymerase chain reaction(qRT-PCR). and the changes in expression position of Notch intracellular domain(NICD) and expression amount of target gene, hairy enhancer of split 1(Hes1) were detected by Immunofluorescence. Then, Activated and inhibited the Notch signaling pathway while induction, and detected mRNA expression of hAMSCs epithelial markers by quantitative real-time polymerase chainreaction (qRT-PCR) respectively and detected hAMSCs cell cycle by flow cytometric. Results:This study showed that hAMSCs alone or combined with E2 could promote endometrial repair, and Notch signaling pathway a great role in it. And otherwise, the activation or habitation of Notch signaling pathway determines whether hAMSCs could differentiate into endometrial epithelial cells or not.Conclusion: we concluded that activate the Notch signaling pathway promote the differentiation of hAMSCs into endometrial epithelial cells, and further treat IUAs.

scholarly journals Effects of Notch Signaling Pathway in Cervical Cancer by Curcumin Mediated Photodynamic Therapy and Its Possible Mechanisms in Vitro and in Vivo

2019 ◽  
Vol 10 (17) ◽  
pp. 4114-4122 ◽  
Author(s):  
Guifang He ◽  
Tianlong Mu ◽  
Yali Yuan ◽  
Wenyan Yang ◽  
Yuan Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Photodynamic Therapy ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway

Resveratrol can inhibit Notch signaling pathway to improve spinal cord injury

2019 ◽  
Vol 223 ◽  
pp. 100-107 ◽  
Author(s):  
Songou Zhang ◽  
Benson O.A. Botchway ◽  
Yong Zhang ◽  
Xuehong Liu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Cord Injury

Circ-Ctnnb1 regulates neuronal injury in spinal cord injury through Wnt/β-catenin signaling pathway

2021 ◽  
Author(s):  
Jialong Qi ◽  
Tao Wang ◽  
Zhidong Zhang ◽  
Zongsheng Yin ◽  
Yiming Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Rat Model ◽  
Cell Model ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Cord Injury

Study design: Spinal cord injury (SCI) rat model and cell model were established for in vivo and in vitro experiments. Functional assays were utilized to explore the role of the circRNAs derived from catenin beta 1 (mmu_circ_0001859, circ-Ctnnb1 herein) in regulating neuronal cell viability and apoptosis. Bioinformatics analysis and mechanism experiments were conducted to assess the underlying molecular mechanism of circ-Ctnnb1. Objective: We aimed to probe into the biological function of circ-Ctnnb1 in neuronal cells of SCI. Methods: The rat model of SCI and hypoxia-induced cell model were constructed to examine circ-Ctnnb1 expression in SCI through quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). Basso, Beattie and Bresnahan (BBB) score was utilized for evaluating the neurological function. Terminal-deoxynucleoitidyl Transferase Mediated Nick End labeling (TUNEL) assays were performed to assess the apoptosis of neuronal cells. RNase R and Actinomycin D (ActD) were used to treat cells to evaluate the stability of circ-Ctnnb1. Results: Circ-Ctnnb1 was highly expressed in SCI rat models and hypoxia-induced neuronal cells, and its deletion elevated the apoptosis rate of hypoxia-induced neuronal cells. Furthermore, circ-Ctnnb1 activated the Wnt/β-catenin signaling pathway via sponging mircoRNA-205-5p (miR-205-5p) to up-regulate Ctnnb1 and Wnt family member 2B (Wnt2b). Conclusion: Circ-Ctnnb1 promotes SCI through regulating Wnt/β-catenin signaling via modulating the miR-205-5p/Ctnnb1/Wnt2b axis.

scholarly journals Protective Effects of CISD2 and Influence of Curcumin on CISD2 Expression in Aged Animals and Inflammatory Cell Model

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 700 ◽  
Author(s):  
Chai-Ching Lin ◽  
Tien-Huang Chiang ◽  
Yu-Yo Sun ◽  
Muh-Shi Lin
Keyword(s):  
Spinal Cord ◽  
Mitochondrial Dysfunction ◽  
Cell Model ◽  
Neural Cells ◽  
Protective Effects ◽  
Curcumin Treatment ◽  
Cord Injury

Background: Inflammation and mitochondrial dysfunction have been linked to trauma, neurodegeneration, and aging. Impairment of CISD2 expression may trigger the aforementioned pathological conditions in neural cells. We previously reported that curcumin attenuates the downregulation of CISD2 in animal models of spinal cord injury and lipopolysaccharide (LPS)-treated neuronal cells. In this study, we investigate (1) the role of CISD2 and (2) how curcumin regulates CISD2 in the aging process. Materials and methods: The serial expression of CISD2 and the efficacy of curcumin treatment were evaluated in old (104 weeks) mice and long-term cultures of neural cells (35 days in vitro, DIV). LPS-challenged neural cells (with or without siCISD2 transfection) were used to verify the role of curcumin on CISD2 underlying mitochondrial dysfunction. Results: In the brain and spinal cord of mice aged P2, 8, 25, and 104 weeks, we observed a significant decrease in CISD2 expression with age. Curcumin treatment in vivo and in vitro was shown to upregulate CISD2 expression; attenuate inflammatory response in neural cells. Moreover, curcumin treatment elevated CISD2 expression levels and prevented mitochondrial dysfunction in LPS-challenged neural cells. The beneficial effects of curcumin in either non-stressed or LPS-challenged cells that underwent siCISD2 transfection were significantly lower than in respective groups of cells that underwent scrambled siRNA-transfection. Conclusions: We hypothesize that the protective effects of curcumin treatment in reducing cellular inflammation associated trauma, degenerative, and aging processes can be partially attributed to elevated CISD2 expression. We observed a reduction in the protective effects of curcumin against injury-induced inflammation and mitochondrial dysfunction in cells where CISD2 expression was reduced by siCISD2.

scholarly journals Gal-3 is a potential biomarker for spinal cord injury and Gal-3 deficiency attenuates neuroinflammation through ROS/TXNIP/NLRP3 signaling pathway

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Zhouliang Ren ◽  
Weidong Liang ◽  
Jun Sheng ◽  
Chuanhui Xun ◽  
Tao Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
In Vitro Model ◽  
Sd Rat ◽  
Potential Biomarker ◽  
Cord Injury ◽  
Vitro Model

Abstract Spinal cord injury (SCI) often occurs in young and middle-aged population. The present study aimed to clarify the function of Galectin-3 (Gal-3) in neuroinflammation of SCI. Sprague–Dawley (SD) rat models with SCI were established in vivo. PC12 cell model in vitro was induced by lipopolysaccharide (LPS). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Gene chip were used to analyze the expression levels of genes in the signaling pathway. Histological assessment, ELISA and Western blotting were conducted to evaluate the effects of Gal-3 upon the SCI model. In the in vivo SD rat model, Gal-3 expression level was up-regulated. The inhibition of Gal-3 attenuated the neuroinflammation in SCI model. The inhibition of Gal-3 could also mitigate the neuroinflammation and reactive oxygen species (ROS) in in vitro model. ROS reduced the effect of Gal-3 on oxidative stress in in vitro model. Down-regulating the content of TXNIP decreased the effect of Gal-3 on neuroinflammation in in vitro model. Suppressing the level of NLRP3 could weaken the effect of Gal-3 on neuroinflammation in in vitro model. Our data highlight that the Gal-3 plays a vital role in regulating the severity of neuroinflammation of SCI by enhancing the activation of ROS/TXNIP/NLRP3 signaling pathway. In addition, inflammasome/IL-1β production probably acts as the therapeutic target in SCI.

scholarly journals RBP-J Deficiency Promoted The Proliferation and Differentiation of CD133-Positive Ependymal Cells In Vitro and In Vivo Studies

2021 ◽  
Author(s):  
Xin Ye ◽  
Mengyi Li ◽  
Wei Bian ◽  
Junwei Li ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
In Vivo Studies ◽  
Ependymal Cells ◽  
Ependymal Layer ◽  
Proliferation And Differentiation ◽  
Mature Neurons

Abstract Although the ependymal cells were reported to have the characteristics of neural stem cells (NSCs), the properties of CD133-ependymal cells have not been uncovered, in particular, it is largely unknown about the effect of Notch signaling pathway on the neurogenesis of CD133-positive ependymal cells. By using the transgenic mouse and primarily cultured ependymal cells, we found that the immunoreactivity for prominin-1/CD133 was exclusively localized in the subventricular zone (SVZ) and ependymal layer of ventricles, moreover, most CD133-positive ependymal cells were co-labeled with Nestin. In addition, RBP-J, a key nuclear effector of Notch signaling pathway, was highly active in CD133-positive ependymal cells. Our results demonstrated that CD133-positive ependymal cells can differentiate into the immature and mature neurons, in particular, the number of CD133-positive ependymal cells differentiating into the immature and mature neurons was significantly increased following the deficiency or interference of RBP-J in vivo or in vitro. By using real-time qPCR and Western blot, we found that RBP-J and Hes1 were down-regulated while Notch1 was up-regulated in the expression levels of mRNAs and proteins following the deficiency or interference of RBP-J in vivo or in vitro. These results demonstrated RBP-J deficiency promoted the proliferation and differentiation of CD133-positive ependymal cells. Therefore, we speculated that RBP-J could maintain CD133-positive ependymal cells in the characteristics of NSCs possibly by regulating Notch1/RBP-J/Hes1 pathway.

scholarly journals Corilagin suppresses cholangiocarcinoma progression through Notch signaling pathway in vitro and in vivo

2016 ◽  
Vol 48 (5) ◽  
pp. 1868-1876 ◽  
Author(s):  
YUE GU ◽  
LINFENG XIAO ◽  
YANLIN MING ◽  
ZHIZHONG ZHENG ◽  
WENGANG LI
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway
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