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The clinicopathological features of early gastric cancer (EGC) with mixed-type histology (differentiated and undifferentiated) are incompletely understood, and the capacity of endoscopic submucosal dissection (ESD) to treat mixed-type cancer remains controversial. This systematic review analyzed the rate of lymph node metastasis (LNM) in mixed-type EGC. We gathered articles published up to February 21, 2021, that analyzed the relationship between LNM and mixed-type EGC from Embase, PubMed, and Web of Science. The primary outcome was the LNM rate associated with different histological types of EGC, and the secondary outcomes were the odds ratios (ORs) for LNM risk factors among EGC patients. From the 24 studies included in this meta-analysis, the overall rate of LNM in predominantly differentiated mixed-type (MD) EGC was 12%, whereas the LNM rate in predominantly undifferentiated mixed-type (MU) EGC was 22%. We further divided these studies into 2 groups according to the depth of invasion. In mixed-type mucosal EGC, the pooled LNM rate was 15%; in submucosal EGC, the rate was 33% for MU, which was higher than the rates for pure types (pure differentiated type, 13%; pure undifferentiated type, 21%; p

Mesenchymal stem cells (MSCs) play an important role in cutaneous wound healing; however, the functional mechanisms involved in the healing process are poorly understood. A series of studies indicate that keratinocytes that migrate into the wound bed rely on an epithelial-mesenchymal transition (EMT)-like process to initiate re-epithelialization. We therefore examined whether bone marrow-derived MSCs (BMSCs) could affect biological behavior and induce EMT-like characteristics in the human epidermal keratinocytes (HEKs) and in the immortalized human keratinocyte cell line HaCaT cells, and we investigated the signaling pathways of BMSC-mediated phenotypic changes. By assessing the expression of EMT-related markers including E-cadherin, α-SMA, and Snail family transcription factors by β2-adrenergic receptor (β2-AR) blockage using ICI-118,551, a β2-AR selective antagonist, or β2-AR small interfering RNA (siRNA), we showed an involvement of β2-AR signaling in the induction of EMT-like alterations in human keratinocytes in vitro. β2-AR signaling also affected collective and individual cell migration in human keratinocyte cell lines, which was attenuated by administration of ICI-118,551. Treating the cells with BMSC-conditioned media (BMSC-CM) not only recapitulated the effect of isoproterenol (ISO) on cell migration but also induced the expression of β2-AR and a panel of proteins associated with mesenchymal phenotype in HEKs and HaCaT cells. Similarly, a blockade of the β2-AR by either ICI-118,551 or β2-AR siRNAs reversed both responses of the epidermal keratinocyte cell lines relative to BMSC-CM exposure. These results were further verified in our vivo findings and indicated that the exogenous application of MSCs promoted cutaneous wound healing and endowed the keratinocytes surrounding the wound area with an increased migratory phenotype through activation of β2-AR signaling. Our findings suggest a biochemical mechanism underlying the function of MSCs in wound re-epithelization, which provides a reliable theoretical basis for the wide application of MSCs in the treatment of chronic wounds.

Mesenchymal stem cells (MSCs) play an important role in cutaneous wound healing; however, the functional mechanisms involved in the healing process are poorly understood. A series of studies indicate that keratinocytes that migrate into the wound bed rely on an epithelial-mesenchymal transition (EMT)-like process to initiate re-epithelialization. We therefore examined whether bone marrow-derived MSCs (BMSCs) could affect biological behavior and induce EMT-like characteristics in the human epidermal keratinocytes (HEKs) and in the immortalized human keratinocyte cell line HaCaT cells, and we investigated the signaling pathways of BMSC-mediated phenotypic changes. By assessing the expression of EMT-related markers including E-cadherin, α-SMA, and Snail family transcription factors by β

Immunofluorescence staining of Ki67 for stabilized re-epithelialization site. (PPTX 4167 kb)

Identification of BM-MSCs. Flow cytometry analysis was used to identify phenotypes of BM-MSCs. The cells were labeled with the following biomarkers: FITC-conjugated anti-HLA-DR, anti-CD34, anti-CD45, anti-CD90, and PE-conjugated anti-CD73, and anti-CD90. BM-MSCs were positive for all three MSCs biomarkers, but negative for hematological, pan-leukocyte and HLA-DR markers (A). Multipotent differentiation capacity of BM-MSCs. BM-MSCs were cultured in osteogenic and adipogenic induction medium for 4 weeks. The differentiated cells were positive by specific methods: alkaline phosphatase for osteogenic cells (B) and Oil Red O for adipogenic cells (C). Scale bars = 50 μm. (PPTX 1177 kb)

Hematoxylin and eosin staining for paw re-epithelialization after scald injury. The paws of each mice treated with or without Dox-induced dCas9-E BM-MSCs were collected after scald injury for 7 to 21Â days. The complete healing epithelial layer is labeled with a dotted line. (PPTX 2327 kb)

Background Patients with a deep burn injury are characterized by losing the function of perspiration and being unable to regenerate the sweat glands. Because of their easy accession, multipotency, and lower immunogenicity, bone marrow-derived mesenchymal stem cells (BM-MSCs) represent as an ideal biological source for cell therapy. The aim of this study was to identify whether targeting the promotor of ectodysplasin (EDA) by CRISPR/dCas9-effector (dCas9-E) could induce the BM-MSCs to differentiate into sweat gland-like cells (SGCs). Methods Activation of EDA transcription in BM-MSCs was attained by transfection of naive BM-MSCs with the lenti-CRISPR/dCas9-effector and single-guide RNAs (sgRNAs). The impact of dCas9-E BM-MSCs on the formation of SGCs and repair of burn injury was identified and evaluated both in vitro and in a mouse model. Results After transfection with sgRNA-guided dCas9-E, the BM-MSCs acquired significantly higher transcription and expression of EDA by doxycycline (Dox) induction. Intriguingly, the specific markers (CEA, CK7, CK14, and CK19) of sweat glands were also positive in the transfected BM-MSCs, suggesting that EDA plays a critical role in promoting BM-MSC differentiation into sweat glands. Furthermore, when the dCas9-E BM-MSCs with Dox induction were implanted into a wound in a laboratory animal model, iodine-starch perspiration tests revealed that the treated paws were positive for perspiration, while the paws treated with saline showed a negative manifestation. For the regulatory mechanism, the expression of downstream genes of NF-κB (Shh and cyclin D1) was also enhanced accordingly. Conclusions These results suggest that EDA is a pivotal factor for sweat gland regeneration from BM-MSCs and may also offer a new approach for destroyed sweat glands and extensive deep burns. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0758-0) contains supplementary material, which is available to authorized users.