Interleukin-10 delivered by mesenchymal stem cells attenuates experimental autoimmune myocarditis.

BACKGROUNDS: Autoimmune myocarditis is characterized by over-activated immune system attacking the cardiomyocytes, resulting in heart function decline. In the current study, we investigated the therapeutic advantages of delivering Interleukin-10 (IL-10) by mesenchymal stem cells (MSCs), both of which had immune suppression functions, in treating experimental autoimmune myocarditis. METHODS: The mouse model of autoimmune myocarditis was established by subcutaneous injection of troponin I in A/J mice. Mouse bone marrow derived mesenchymal stem cells (BM-MSCs) with or without IL-10 overexpression, or the recombinant IL-10 protein were delivered into the mice via tail-vein injection. The inflammation and fibrosis levels of the heart were evaluated with qPCR, ELISA and histological staining. Serum level of anti-troponin-I was assessed by ELISA. Heart function analysis was conducted with echocardiography. RESULTS: BM-MSCs overexpressing IL-10 had enhanced immune suppression functions. They also showed improved therapeutic effects from the perspective of heart function and cardiac fibrosis. The anti-troponin-I level was significantly reduced by MSCs overexpressing IL-10 when comparing with the MSCs or IL-10 protein injection. CONCLUSION: IL-10 delivered by MSCs showed therapeutic advantages in treating experimental autoimmune myocarditis.

Combined prediction of miR-210 and miR-374a for severity and prognosis of hypoxic-ischemic encephalopathy.

Background and Aim: Hypoxic-ischemic encephalopathy (HIE) is a disorder featured by hypoxic and ischemic damages during the perinatal period and its high mortality (i.e., 15%-20%) could be partly attributed to late diagnosis. Therefore, miR-210 and miR-374a were investigated to find if they could improve the diagnostic values of S100B protein and neuron-specific enolase (NSE) for HIE. Methods: Altogether 167 HIE newborns and 82 healthy newborns were recruited, and their blood were sampled for determining the levels of biomarkers. Specifically, S100B protein and NSE levels were detected based on the enzyme-linked immunosorbent assay (ELISA) kit, while the expressions of miR-210 and miR-374a were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, the receiver operating characteristic (ROC) curves were established to assess the diagnostic values of the above biomarkers for HIE. Finally, the correlation analysis between miR-210/miR-374 and Neonatal Behavioral Neurological Assessment (NBNA) scoring or Gesell intellectual development were also conducted. Results: The levels of miR-210, miR-374a, S100B protein, and NSE were significantly distinct between HIE patients and healthy newborns (p < .05). Besides, miR-210 (rs = .573), miR-374a (rs = .651), NSE level (rs = -.622), and S100B level (rs = -.55) were all, respectively, correlated with NBNA scoring with statistical significance (p < .05). Furthermore, it was revealed that the combined diagnosis of miR-210, miR-374a, S100B protein, and NSE could obtain the highest accuracy regarding pairs of mild HIE versus moderate HIE (AUC = 0.898), moderate HIE versus severe HIE (AUC = 0.922), mild HIE versus severe HIE (AUC = 0.996), and HIE versus control (AUC = 0.960). More than that, the four molecules were also remarkably associated with Gesell intellectual development (p < .05). Conclusion: MiR-210 and miR-374a could help to elevate the diagnostic value and prognostic prediction of S100B protein and NSE for HIE.

Promotion of Wilms' tumor cells migration and invasion by mono-2-ethyhexyl phthalate (MEHP) via activation of NF-κB signals.

Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5-10% of cases. There is an urgent need to illustrate risk factors which can trigger the motility of Wilms tumor cells. Our present study revealed that mono-(2-ethylhexyl) phthalate (MEHP) exposure can significantly increase the in vitro migration and invasion of G401 and WiT49 cells. Real time PCR and western blot analysis revealed that MEHP treatment can increase the expression of metalloproteinase-2 (MMP-2) and MMP-9, while had no effect on the expression of MMP-1, MMP-3, or MMP-12. The si-MMP-2 and si-MMP-9 can reverse MEHP induced migration and invasion of G401 cells. MEHP can activate both ERK1/2 and p65 in WT cells, while had no obvious effect on Akt or PKA. However, only BAY 11-7082, the inhibitor of NF-κB, while not ERK1/2 (PD 98059), can reverse MEHP induced migration and invasion of WT cells. BAY 11-7082 also can attenuate MEHP induced up regulation of MMP-2 and MMP-9. The inhibitor of estrogen receptor reversed MEHP induced activation of NF-κB and up regulation of MMP-2/-9. In addition, MEHP also increased the mRNA and protein expression, nuclear translocation, and transcriptional activities of NF-κB in WT cells. Collectively, our study found that MEHP stimulated the Wilms' tumor progression via NF-κB signals.