Mineral trioxide aggregate promoted odonto/osteogenic capacity of craniofacial BMSCs via JNK and ERK MAPK signalling pathways.

IL-35 is a newly discovered inhibitory cytokine secreted by regulatory T cells (Tregs) and may have therapeutic potential in several inflammatory disorders. Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation and caused by donor T cells and inflammatory cytokines. The role of IL-35 in aGVHD is still unknown. Here we demonstrate that IL-35 overexpression suppresses CD4+ effector T cell activation, leading to a reduction in alloreactive T-cell responses and aGVHD severity. It also leads to the expansion of CD4+Foxp3+ Tregs in the aGVHD target organs. Furthermore, IL-35 overexpression results in a selective decrease in the frequency of Th1 cells and an increase of IL-10-producing CD4+ T cells in aGVHD target tissues. Serum levels of TNF-α, IFN-γ, IL-6, IL-22 and IL-23 decrease and IL-10 increases in response to IL-35. Most importantly, IL-35 preserves graft versus leukemia effect. Finally, aGVHD grade 2-4 patients have decreased serum IL-35 levels comparing with time-matched patients with aGVHD grade 0-1. Our findings indicate that IL-35 plays an important role in reducing aGVHD through promoting the expansion of Tregs and repressing Th1 responses, and should be investigated as the therapeutic strategy for aGVHD.

Mineral trioxide aggregate enhances the odonto/osteogenic capacity of DPSCs from inflammatory sites via activating the NF-κB pathway.

No abstract

The pathology underlying schizophrenia (SCZ) involves cell type-specific and developmental stage-specific dysregulation of multiple gene regulatory networks dominated by some key transcription factors, such as SCZ risk gene transcription factor 4 (TCF4). Previous studies on the regulatory mechanism of TCF4 use SY5Y as the cellular model, which could not reflect its cell type-specific role in the real world. Using the transcriptional profile of whole brain during development stages and single-cell transcriptome data in the developing human prefrontal cortex, we found that TCF4 was preferentially expressed in the interneuron. Chromatin immunoprecipitation combined with sequencing (ChIP-Seq) in human embryonic stem cells (hESC)-derived interneurons revealed that TCF4 primarily activate transcription of genes associated with cortex development and telencephalon regionalization in a long-range manner. As expected, the downstream targets of TCF4 were distinct in inhibitory neurons and neural stem cells during early neurodevelopment, justifying the importance of our study. Deeper investigation further revealed that TCF4 regulate genes related to neurotransmission distally in interneuron in a c-FOS dependent manner, while TCF4 and TCF3 synergistically regulate genes associated with cell proliferation associated proximally in neural stem cells. Our findings suggested that defects in development of interneuron, for instance as a result of TCF4 abnormality, may break excitation and inhibition balance and contribute significantly to the risk of SCZ.