Stem cells from exfoliated deciduous teeth (SHED) possess multipotent differentiation and immunomodulatory properties. They have been used for orofacial bone regeneration and autoimmune disease treatment. In this study, we show that acetylsalicylic acid (ASA) treatment is able to significantly improve SHED-mediated osteogenic differentiation and immunomodulation. Mechanistically, ASA treatment upregulates the telomerase reverse transcriptase (TERT)/Wnt/β-catenin cascade, leading to improvement of SHED-mediated bone regeneration, and also upregulates TERT/FASL signaling, leading to improvement of SHED-mediated T-cell apoptosis and ameliorating disease phenotypes in dextran sodium sulfate-induced colitis mice. These data indicate that ASA treatment is a practical approach to improving SHED-based cell therapy.
BackgroundThe symptoms of major depression (MD) are clinically diverse. Do they form coherent factors that might clarify the underlying nature of this important psychiatric syndrome?MethodSymptoms at lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years with recurrent DSM-IV MD. Exploratory factor analysis (EFA) and confirmatoryfactor analysis (CFA) were performed in Mplus in random split-half samples.ResultsThe preliminary EFA results were consistently supported by the findings from CFA. Analyses of the nine DSM-IV MD symptomatic A criteria revealed two factors loading on: (i) general depressive symptoms; and (ii) guilt/suicidal ideation. Examining 14 disaggregated DSM-IV criteria revealed three factors reflecting: (i) weight/appetite disturbance; (ii) general depressive symptoms; and (iii) sleep disturbance. Using all symptoms (n = 27), we identified five factors that reflected: (i) weight/appetite symptoms; (ii) general retarded depressive symptoms; (iii) atypical vegetative symptoms; (iv) suicidality/hopelessness; and (v) symptoms of agitation and anxiety.ConclusionsMD is a clinically complex syndrome with several underlying correlated symptom dimensions. In addition to a general depressive symptom factor, a complete picture must include factors reflecting typical/atypical vegetative symptoms, cognitive symptoms (hopelessness/suicidal ideation), and an agitated symptom factor characterized by anxiety, guilt, helplessness and irritability. Prior cross-cultural studies, factor analyses of MD in Western populations and empirical findings in this sample showing risk factor profiles similar to those seen in Western populations suggest that our results are likely to be broadly representative of the human depressive syndrome.
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.
Aim
To investigate the in vitro biological effects of a nanoparticle bioceramic material, iRoot Fast Set root repair material (iRoot FS), on the proliferation, migration and osteo/odontogenic differentiation of human stem cells from the apical papilla (hSCAP), and to further explore the mechanism involved in osteo/odontogenic induction of iRoot FS.
Methodology
hSCAP were isolated and characterized in vitro. iRoot FS conditioned medium were prepared and used to treat hSCAP, while using mineral trioxide aggregate (MTA) conditioned medium as the positive control and regular medium as the negative control. MTT assay and BrdU labelling assay were performed to determine cell proliferation. Wound healing assay and transwell assay were conducted to evaluate cell migration. The osteo/odontogenic differentiation of hSCAP was evaluated by qPCR, Western blot and Alizarin red S staining. Wnt inhibitor was used for downregulating the expression level of β‐catenin of hSCAP.
Results
The cell proliferation of hSACP in the iRoot FS group was not significantly different compared with the control groups. The cell migration of hSCAP in the iRoot FS group was significantly increased than the MTA and negative control groups (P < 0.01). The expression levels of osteo/odontogenic markers and mineralization nodule formation of hSCAP in the iRoot FS group were significantly elevated (P < 0.01). Furthermore, iRoot FS enhanced the osteo/odontogenic differentiation of hSCAP by activating Wnt/β‐catenin signalling.
Conclusions
iRoot FS promoted the cell migration of hSCAP and enhanced their oseto/odontogenesis potential via the Wnt/β‐catenin pathway without cytotoxicity. iRoot FS had satisfactory biological properties and has potential to be used as an apical barrier in apexification or as a coronal sealing material in regenerative endodontic treatment.
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