This study tested the hypothesis that MMP-9^−/−tPA^−/− double knock out (i.e., MT^DKO) plays a crucial role in the prognostic outcome after acute myocardial infarction (AMI by ligation of left-coronary-artery) in MT^DKO mouse. Animals were categorized into sham-operated controls in MT^DKO animals (group 1) and in wild type (B6: group 2), AMI-MT^DKO (group 3) and AMI-B6 (group 4) animals. They were euthanized, and the ischemic myocardium was harvested, by day 60 post AMI. The mortality rate was significantly higher in group 3 than in other groups and significantly higher in group 4 than in groups 1/2, but it showed no difference in the latter two groups (all p < 0.01). By day 28, the left-ventricular (LV) ejection fraction displayed an opposite pattern, whereas by day 60, the gross anatomic infarct size displayed an identical pattern of mortality among the four groups (all p < 0.001). The ratio of heart weight to tibial length and the lung injury score exhibited an identical pattern of mortality (p < 0.01). The protein expressions of apoptosis (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP), fibrosis (Smad3/T-GF-ß), oxidative stress (NOX-1/NOX-2/oxidized-protein), inflammation (MMPs^2,9/TNF-α/p-NF-κB), heart failure/pressure overload (BNP/ß-MHC) and mitochondrial/DNA damage (cytosolic-cytochrome-C/γ-H2AX) biomarkers displayed identical patterns, whereas the angiogenesis markers (small vessel number/CD31+cells in LV myocardium) displayed opposite patterns of mortality among the groups (all p < 0.0001). The microscopic findings of fibrotic/collagen deposition/infarct areas and inflammatory cell infiltration of LV myocardium were similar to the mortality among the four groups (all p < 0.0001). MT^DKO strongly predicted unfavorable prognostic outcome after AMI.

This study tested whether the soluble (s)ST2 is a superb biomarker predictive of moderate to severe cerebral–cardiac syndrome (CCS) (defined as coexisting National Institute of Health Stroke Scale (NIHSS) >8 and left-ventricular ejection fraction (LVEF) <60%) in patients after acute ischemic stroke (IS). Between November 2015 and October 2017, a total of 99 IS patients were prospectively enrolled and categorized into three groups based on NIHSS, i.e., group 1 (NIHSS ≤ 8, n = 66), group 2 (NIHSS = 9-15, n = 14) and group 3 (NIHSS ≥ 16, n = 19), respectively. Blood samples were collected immediately after hospitalization, followed by transthoracic echocardiographic examination. The results showed that the flow cytometric analysis for assessment of inflammatory biomarkers of TLR2+/CD14+cells, TLR4+/CD14+cells, Ly6g+/CD14+cells, and MPO+/CD14+cells, and ELISA assessment for circulatory level of sST2 were significantly higher in groups 2/3 than in group 1 (all p < 0.01). However, these parameters did not show significant differences between groups 2 and 3 (all p > 0.05). The LVEF was significantly lower in group 3 than in group 1 (p < 0.001), but it displayed no difference between groups 1/2 or between groups 2/3. These inflammatory biomarkers ((TLR2+/CD14+cells// TLR4+/CD14+cells// MPO+/CD14+cells) and sST2)) were significantly positively correlated to NIHSS and strongly negatively correlated to LVEF (all p < 0.05). Multivariate analysis demonstrated that both MPO/CD14+cells >20% (p = 0.027) and sST2 ≥ 17,600 (p = 0.004) were significantly and independently predictive of moderate-severe CCS after acute IS. Receiver operating characteristic curve analysis demonstrated that sST2 was the most powerful predictor of CCS with a sensitivity of 0.929 and a specificity of 0.731 (p < 0.001). In conclusion, sST2 is a useful biomarker for prediction of CCS severity in patients after acute IS.

Background: This study investigated whether the double overexpression of decorin and IL-10 in human bone marrow-derived mesenchymal stem cells [HBMDMSCs ^{DO (DEC/IL-10)} ] can protect against bleomycin (BLM)-induced pulmonary fibrosis (PF) in mice. Methods: L2 and NR8383 cells were treated with BLM (0–2.5 μg/mL). In vivo , animals were assigned to four groups: Group 1 – sham control (SC); Group 2 – PF; Group 3 – PF + HBMDMSCs; Group 4 – PF + HBMDMSCs ^{DO (DEC/IL-10)} . Results: BLM, at its IC ₅₀ , significantly reduced the viability of L2 and NR8383 cells while increasing early and late apoptosis and TGF-β expression ( P < 0.001). BLM treatment in L2 cells induced oxidative stress (mitochondrial ROS, NOXs/p22 ^phox ), cell-stress signaling (MAPKs), and epithelial–mesenchymal transition (EMT) biomarkers, which were reversed by decorin, HBMDMSCs, decorin-overexpressing HBMDMSCs, or p22 ^phox silencing ( P < 0.001). Decorin silencing in L2 and CG1629 cells upregulated EMT and cell-stress markers, effects reversed by decorin treatment, decorin overexpression, or MSC ^{DO (DEC/IL-10)} ( P < 0.001). In BLM-induced PF mice, SaO ₂ was highest in Group 1, lowest in Group 2, and higher in Group 4 than Group 3, while lung injury, fibrosis, right-ventricular pressure, and inflammatory cells showed the opposite trend ( P < 0.0001). Lung expression of EMT/proliferation (c-Myc, Cyclin D/E, Wnt/β-catenin), oxidative stress (p22 ^phox , OxyBlot), and fibrosis (TGF-β, p-Smad3) proteins mirrored lung injury scores ( P < 0.0001). Conclusion: HBMDMSCs ^{DO (DEC/IL-10)} treatment effectively protected the lungs from BLM-induced PF in rodents.