BackgroundChromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L), also known as ALC1 (amplified in liver cancer 1 gene), is a new oncogene amplified in many solid tumors. Whether this gene plays a role in invasion and metastasis of breast cancer is unknown.MethodsImmunohistochemistry was performed to detect the expression of CHD1L in patients with invasive ductal carcinoma and normal mammary glands. Chemotaxis, wound healing, and Transwell invasion assays were also performed to examine cell migration and invasion. Western blot analysis was conducted to detect the expression of CHD1L, MMP-2, MMP-9, pAkt/Akt, pARK5/ARK5, and pmTOR/mTOR. Moreover, ELISA was carried out to detect the expression levels of MMP-2 and MMP-9. Nude mice xenograft model was used to detect the invasion and metastasis of breast cancer cell lines.ResultsCHD1L overexpression was observed in 112 of 268 patients (41.8%). This overexpression was associated with lymph node metastasis (P = 0.008), tumor differentiation (P = 0.020), distant metastasis (P = 0.026), MMP-2 (P = 0.035), and MMP-9 expression (P = 0.022). In the cell experiment, reduction of CHD1L inhibited the invasion and metastasis of breast cancer cells by mediating MMP-2 and MMP-9 expression. CHD1L knockdown via siRNA suppressed EGF-induced pAkt, pARK5, and pmTOR. This knockdown inhibited the metastasis of breast cancer cells into the lungs of SCID mice.ConclusionsCHD1L promoted the invasion and metastasis of breast cancer cells via the PI3K/Akt/ARK5/mTOR/MMP signaling pathway. This study identified CHD1L as a potential anti-metastasis target for therapeutic intervention in breast cancer.

The effects of transplanting bone marrow mesenchymal stromal cells (BMSCs) for the treatment of white matter damage are not well understood, nor are the underlying mechanisms. Recent studies showed that endogenous oligodendrocyte progenitor cells (OPCs) can be stimulated to proliferate. Therefore, we explore the effects of BMSCs transplantation on white matter damage and the proliferation of OPCs in transient focal cerebral ischemic rats. BMSCs were transplanted into a group of rats that had undergone middle cerebral artery occlusion (MCAO) 24 h after reperfusion. The ratswere examined by MRI-T2 and DTI sequencesdynamically. The proliferating cells were labeled by 5-Bromo-2'-deoxyuridine (BrdU). The effects of BMSC transplantation on neurons, axons, myelination, and proliferating OPCs were examined by Nissl staining, MBP/NF-H and BrdU/NG2 immunofluorescence staining7 days after transplantation. More Nissl-stained neuronswere found and the FA value of MRI-DTI was significantly higher in the MCAO + BMSCs group than in the MCAOgroup (both P < .01). The fold change of MBP protein was significantly higher in the MCAO + BMSCs group than in the MCAO group (P < .01); the same was true of NF-H protein. Additionally, there were more BrdUNG2 cells in the SVZ areas of the MCAO + BMSCs group than in the MCAO group (P < .01). BMSCs thus were shown to alleviate neuronal/axonal injury and promote the proliferation of OPCs and formation of myelin sheath, significantly alleviating white matter damage in focal cerebral ischemic rats.

Background Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model. Methods LPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved. Results Rev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF-α and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS. Conclusions These findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway. Electronic supplementary material The online version of this article (10.1186/s12931-019-1099-6) contains supplementary material, which is available to authorized users.

SummaryThe anti-contractile property of perivascular adipose tissue (PVAT) is abolished through an endothelium-dependent pathway in obesity. C1q/tumor necrosis factorrelated protein (CTRP)9 improved endothelial function by promoting endotheliumdependent vasodilatation. The aims of this study were to investigate whether CTRP9 improves the anti-contractile effect of PVAT and protects against PVAT dysfunction in obese mice. The mice were treated with a high-fat diet with or without CTRP9 treatment. Thoracic aortas with or without PVAT (PVAT+ or PVAT−) were prepared, and concentration-dependent responses to phenylephrine were measured. Obese mice showed a significantly increased contractile response, which was suppressed by CTRP9 treatment both with and without PVAT. PVAT significantly reduced the anticontractile effect in obese mice, which was partially restored by CTRP9 treatment. Treatment of the aortic rings (PVAT+) with inhibitors of AMP protein kinase (AMPK),Akt and endothelial nitric oxide synthase (eNOS) attenuated the beneficial effect of CTRP9 on PVAT. Similar results were observed when we pretreated the aortic rings with CTRP9 ex vivo. CTRP9 significantly enhanced the phosphorylation levels of AMPK, Akt and eNOS, and reduced superoxide production and TNF-α levels in PVAT from obese mice. Our study suggests that CTRP9 enhanced the anti-contractile effect of PVAT and improved PVAT function by activating the AMPK-eNOS pathway in obese mice.