Skin is the largest organ of the human body. Skin wound is one of the most common forms of wound. Mesenchymal stromal cells (MSCs) have been used to aid skin wound healing via their paracrine factors. Because the secretome of MSCs can be greatly enriched and amplified by treatment with IFN-γ and TNF-α (IT), we here tested whether supernatant derived from MSCs pretreated with IT, designated as S-MSCs-IT, possesses improved wound healing effect by using a murine model of cutaneous excision, S-MSCs-IT was found to be more potent in promoting angiogenesis, constricting collagen deposition and accelerating wound closure than control supernatant (S-MSCs) during the healing of skin wound. VEGFC, but not VEGFA, was greatly upregulated by IT and was found to be a key factor in mediating the improved wound healing effect of S-MSCs-IT. Our results indicate that the beneficial paracrine effect of MSCs on wound healing can be enhanced by pretreatment with inflammatory cytokines. IT treatment may represent a new strategy for optimizing the therapeutic effect of MSCs on skin injuries.

The dome-shaped cornea is a transparent, non-vascularized, and epithelialized highly organized tissue. Physical and chemical injuries may trigger corneal wound healing (CWH) response and result in neovascularization that impairs the visual function. CWH involves not only migration, proliferation, and differentiation of the cells in different layers of cornea, but also the mobilization of immune cells. We demonstrated here that human adipose-derived mesenchymal stromal cells (ADSCs) could effectively inhibit neovascularization during ethanol-induced injury in mouse cornea. Importantly, we found that while neutrophils are essential for CWH, excessive and prolonged neutrophil retention during the granulation stage contributes to neovascularization. ADSCs were found to promote the clearance of neutrophils in the cornea during the granulation stage, likely via increasing the reverse transendothelial cell migration of CXCR4 high neutrophils from cornea to the lung. Our results demonstrate that ADSCs are effective in treating CWHinduced neovascularization and modulation of neutrophil clearance could be novel strategies for better vision recovery after injury.

Submandibular glands (SMGs) are one of the primary components of salivary glands in goats. The proteins and biologically active substances secreted by the SMGs change with growth and development. Our previous studies showed that most of the differentially expressed genes in the SMGs of goats at different developmental stages are involved in immune-related signaling pathways, but the miRNA expression patterns in the same tissues are unknown. The aim of this study was to reveal the expression profile of miRNAs at three different developmental stages, detect differentially expressed miRNAs (DE miRNAs) and predict disease-related DE miRNAs. SMG tissue samples were collected from groups of 1-month-old kids, 12-month-old maiden goats and 24-month-old adult goats (three samples from each group), and high-throughout transcriptome sequencing was conducted. A total of 178, 241 and 7 DE miRNAs were discovered between 1-month-old kids and 12-month-old maiden goats, between 1-month-old kids and 24-month-old adult goats, and between 12-month-old maiden goats and 24-month-old adult goats, respectively. Among these DE miRNAs, 88 DE miRNAs with medium or high expression levels (TPM ≥50) were classified into five expression pattern clusters. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that some of the predicted target genes of the DE miRNAs in the five clusters were enriched in disease-related GO terms and pathways. MiRNA target genes in significant pathways were significantly enriched in Hepatitis B (FDR = 9.03E-10) and Pathways in cancer (FDR = 4.2E-10). Further analysis was performed with a PPI network, and 10 miRNAs were predicted to play an important role in the occurrence and prevention of diseases during the growth and development of goats.

The occurrence of metastasis is a serious risk for renal cell carcinoma (RCC) patients. In order to develop novel therapeutic approaches to control the progression of metastatic RCC, it is of urgent need to understand the molecular mechanisms underlying RCC metastasis and identify prognostic markers of metastatic risk. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been known to be closely associated with extracellular matrix (ECM) turnover, which plays a highly active role in tumor metastasis. Recent studies have shown that immunophilin FK-506-binding protein 51 (FKBP51) may be important for the regulation of ECM function, and exert effects on the invasion and migration of tumor cells. However, the mechanisms underlying these activities remain unclear. The present study detected the role of FKBP51 in clear cell renal cell carcinoma (ccRCC), the most common subtype of RCC, and found that FKBP51 significantly promotes ccRCC invasion and migration by binding with the TIMP3, connecting TIMP3 with Beclin1 complex and increasing autophagic degradation of TIMP3. Given the important roles that TIMPs/MMPs play in ECM regulation and remodeling, our findings will provide new perspective for future investigation of the regulation of metastasis of kidney cancer and other types of cancer.

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