Association between lactate/albumin ratio and mortality in patients with heart failure after myocardial infarction.

AIMS: Lactate/albumin ratio (L/A) is a recognized prognostic index of patients with heart failure (HF) after myocardial infarction (MI). We aim to evaluate the prognostic value of L/A ratio in predicting in-hospital mortality for those patients. METHODS AND RESULTS: We enrolled qualified patients from Medical Information Mart for Intensive Care IV database for retrospective study. A receiver operating characteristic (ROC) curve of the subjects was applied to determine the predicted value and the best cut-off value of L/A on admission. Univariate/multivariate Cox regression analysis and restricted cubic splines (RCS) were performed to identify the association between hospital admission and hospital mortality. The Kaplan-Meier (KM) method was used to draw the survival curve of the two groups with different L/A levels at admission. L/A values at admission were significantly higher in the death groups than the survival groups [1.36 (1.20) vs. 0.62 (0.36), P < 0.05], and area under the ROC curve [0.780 (95% confidence interval, 0.772-0.827)] was better than other indicators, and the best the cut-off value was 0.671. Data of Cox regression analysis showed that higher L/A value supposed to be an independent risk factor for in-hospital mortality. RCS analysis showed evidence of an increasing trend and a non-linear relationship between L/A and in-hospital mortality (P value was non-linear <0.05). KM survival curves were significantly lower in the high L/A group than the low L/A group (P < 0.001), and the former group had an increased risk of in-hospital mortality compared with the latter one (log rank P < 0.001). CONCLUSIONS: Elevated L/A ratio on admission is an independent predictor of high in-hospital mortality in post-MI heart failure patients, which proved to be better than lactate, Sequential Organ Failure Assessment score and other related indicators.

Adipose mesenchymal stem cells and gingival mesenchymal stem cells have a comparable effect in endothelium repair.

Restenosis is the major factor influencing the long-term success rate of angioplasty and stent implantation and effective strategies to prevent restenosis remain limited. Mesenchymal stem cells (MSCs) are pluripotent stem cells capable of self-renewal and multidirectional differentiation, which may be able to promote endothelium repair, thereby reducing restenosis. The present study aimed to evaluate the effects of adipose MSCs (AMSCs) and gingival MSCs (GMSCs) on endothelium repair. MSCs were isolated from two human tissue types, namely adipose tissue and gingival tissue, and the effects of AMSCs and GMSCs in ex vivo endothelium repair and on vascular smooth muscle cell (SMC) growth were examined. To compare the feasibility of using AMSCs and GMSCs for the repair of endothelium damage in endothelial cell (EC) damage and vasoproliferative disorders, an ex vivo model of endothelium repair in a co-culture system was developed. It was indicated that AMSCs and GMSCs expressed characteristic MSC markers (CD105 and CD166). 3H-thymidine incorporation in the co-culture group of AMSCs and SMCs in the presence of ECs was lower compared with that in the GMSC and SMC co-culture group. The protein expression level of proliferating cell nuclear antigen in the co-culture group of AMSCs and SMCs in the presence of ECs were lower compared with that in the GMSC and SMC co-culture group. After co-culture with ECs for 5 days, 25.71±3.08% of AMSCs began to express CD31 protein and 20.06±2.09% of GMSCs began to express CD31 protein. Furthermore, anti-VEGF antibody was able to inhibit MSC differentiation. Collectively, the present results suggested that seeding of AMSCs had a stronger effect to inhibit the proliferation and migration of SMCs compared with GMSCs.

Cardiac Derived CD51-Positive Mesenchymal Stem Cells Enhance the Cardiac Repair Through SCF-Mediated Angiogenesis in Mice With Myocardial Infarction.

Objective: Many tissues contained resident mesenchymal stromal/stem cells (MSCs) that facilitated tissue hemostasis and repair. However, there is no typical marker to identify the resident cardiac MSCs. We aimed to determine if CD51 could be an optimal marker of cardiac MSCs and assess their therapeutic potential for mice with acute myocardial infarction (AMI). Methods: Cardiac-derived CD51+CD31-CD45-Ter119- cells (named CD51+cMSCs) were isolated from C57BL/6 mice(7-day-old) by flow cytometry. The CD51+cMSCs were characterized by proliferation capacity, multi-differentiation potential, and expression of typical MSC-related markers. Adult C57BL/6 mice (12-week-old) were utilized for an AMI model via permanently ligating the left anterior descending coronary artery. The therapeutic efficacy of CD51+cMSCs was estimated by echocardiography and pathological staining. To determine the underlying mechanism, lentiviruses were utilized to knock down gene (stem cell factor [SCF]) expression of CD51+cMSCs. Results: In this study, CD51 was expressed in the entire layers of the cardiac wall in mice, including endocardium, epicardium, and myocardium, and its expression was decreased with age. Importantly, the CD51+cMSCs possessed potent self-renewal potential and multi-lineage differentiation capacity in vitro and also expressed typical MSC-related surface proteins. Furthermore, CD51+cMSC transplantation significantly improved cardiac function and attenuated cardiac fibrosis through pro-angiogenesis activity after myocardial infarction in mice. Moreover, SCF secreted by CD51+cMSCs played an important role in angiogenesis both in vivo and in vitro. Conclusions: Collectively, CD51 is a novel marker of cardiac resident MSCs, and CD51+cMSC therapy enhances cardiac repair at least partly through SCF-mediated angiogenesis.

Upregulation of MicroRNA-125b Leads to the Resistance to Inflammatory Injury in Endothelial Progenitor Cells.

OBJECTIVES: MicroRNA-125b (miR-125b) has been recognized as one of the key regulators of the inflammatory responses in cardiovascular diseases recently. This study sought to dissect the role of miR-125b in modulating the function of endothelial progenitor cells (EPCs) in the inflammatory environment of ischemic hearts. METHODS: EPCs were cultured and transfected with miR-125b mimic and negative control mimic. Cell migration and adhesion assays were performed after tumor necrosis factor-α (TNF-α) treatment to determine EPC function. Cell apoptosis was analyzed by flow cytometry. The activation of the NF-κB pathway was measured by western blotting. EPC-mediated neovascularization in vivo was studied by using a myocardial infarction model. RESULTS: miR-125b-overexpressed EPCs displayed improved cell migration, adhesion abilities, and reduced cell apoptosis compared with those of the NC group after TNF-α treatment. miR-125b overexpression in EPCs ameliorated TNF-α-induced activation of the NF-κB pathway. Mice transplanted with miR-125b-overexpressed EPCs showed improved cardiac function recovery and capillary vessel density than the ones transplanted with NC EPCs. CONCLUSIONS: miR-125b protects EPCs against TNF-α-induced inflammation and cell apoptosis by attenuating the activation of NF-κB pathway and consequently improves the cardiac function recovery and EPC-mediated neovascularization in the ischemic hearts.

Cardiac Nestin+ Mesenchymal Stromal Cells Enhance Healing of Ischemic Heart through Periostin-Mediated M2 Macrophage Polarization.

Mesenchymal stromal cells (MSCs) show potential for treating cardiovascular diseases, but their therapeutic efficacy exhibits significant heterogeneity depending on the tissue of origin. This study sought to identify an optimal source of MSCs for cardiovascular disease therapy. We demonstrated that Nestin was a suitable marker for cardiac MSCs (Nes+cMSCs), which were identified by their self-renewal ability, tri-lineage differentiation potential, and expression of MSC markers. Furthermore, compared with bone marrow-derived MSCs (Nes+bmMSCs) or saline-treated myocardial infarction (MI) controls, intramyocardial injection of Nes+cMSCs significantly improved cardiac function and decreased infarct size after acute MI (AMI) through paracrine actions, rather than transdifferentiation into cardiac cells in infarcted heart. We further revealed that Nes+cMSC treatment notably reduced pan-macrophage infiltration while inducing macrophages toward an anti-inflammatory M2 phenotype in ischemic myocardium. Interestingly, Periostin, which was highly expressed in Nes+cMSCs, could promote the polarization of M2-subtype macrophages, and knockdown or neutralization of Periostin remarkably reduced the therapeutic effects of Nes+cMSCs by decreasing M2 macrophages at lesion sites. Thus, the present work systemically shows that Nes+cMSCs have greater efficacy than do Nes+bmMSCs for cardiac healing after AMI, and that this occurs at least partly through Periostin-mediated M2 macrophage polarization.

Quantitative Determination of Acetamiprid in Pollen Based on a Sensitive Enzyme-Linked Immunosorbent Assay.

A sensitive biotinylated indirect competitive enzyme-linked immunosorbent assay (Bic-ELISA) was developed to detect acetamiprid pesticides in pollen, based on the heterogeneous coating antigen and biotinylated anti-acetamiprid monoclonal antibody. Under optimized experimental conditions, the detection limit for the Bic-ELISA was 0.17 ng/mL and the linear range was 0.25⁻25 ng/mL. The cross-reactivities could be regarded as negligible for the biotinylated antibodies with their analogues except for thiacloprid (1.66%). Analyte recoveries for extracts of spiked pollen (camellia pollen, lotus pollen, rape pollen) ranged from 81.1% to 108.0%, with intra-day relative standard deviations (RSDs) of 4.8% to 10.9%, and the average reproducibility was 85.4% to 110.9% with inter-assay and inter-assay RSDs of 6.1% to 11.7%. The results of Bic-ELISA methods for the Taobao's website samples were largely consistent with HPLC-MS/MS. Therefore, the established Bic-ELISA methods would be conducive to the monitoring of acetamiprid in pollen.

Cardiac Nestin+ Cells Derived from Early Stage of Dilated Cardiomyopathy Enhanced the Survival of the Doxorubicin-Injured Cardiac Muscle HL-1 Cells.

Dilated cardiomyopathy (DCM), as one of the common cardiomyopathies, is a disease of the heart muscle; however, the etiology and pathogenesis of DCM were still poorly understood. Nestin has been reported a special marker of stem/progenitor cells in various tissues, and the tissue resident Nestin+ cells could promote the wound healing and tissue remodeling. However, it remains unclear whether Nestin+ cells participate in the protection of cardiomyocytes during the pathogenesis of DCM. Here the model of mice DCM was induced by doxorubicin (DOX) intraperitoneal injection and observed heart failure and ventricular enlargement via echocardiography and histologic analysis, respectively. During DCM pathogenesis, the number of Nestin+ cells showed a significant peak on day 6 after DOX treatment, which then gradually decreases to lower than normal levels after day 30 in the total population of the heart. Furthermore, we found that the isolated increased heart-derived Nestin+ cells are mesenchymal property and could protect DOX-induced HL-1 cells toxicity in vitro by promoting their proliferation and inhibiting their apoptosis. Collectively, our results showed that Nestin+ cells increased during DCM pathogenesis and played an important role in protecting against the DOX-induced HL-1 cells loss via regulating proliferation and apoptosis. Thus, the loss of Nestin+ cells might be an etiology to DCM pathogenesis, and these cells could be a promising candidate cell source for study and treatment of DCM patients.

Mesenchymal Stromal Cells Mitigate Experimental Colitis via Insulin-like Growth Factor Binding Protein 7-mediated Immunosuppression.

Mesenchymal stromal cells (MSCs) have shown great potential for treating inflammatory bowel disease, which is ameliorated through paracrine cross talk between MSCs and T-cells. Members of the insulin-like growth factor binding protein (IGFBP) family have important immunomodulatory functions in MSCs, but the underlying mechanisms behind these functions have not yet been clearly elucidated. In this study, we investigate whether MSC-produced IGFBP7 is involved in immune modulation using a mouse experimental colitis model. Gene expression profiling revealed that IGFBP7 was highly expressed in MSCs. Consistent with this findings, IGFBP7 knockdown in MSCs significantly decreased their immunomodulatory properties, decreasing the antiproliferative functions of MSCs against T-cells, while also having an effect on the proinflammatory cytokine production of the T-cells. Furthermore, in the mouse experimental colitis model, MSC-derived IGFBP7 ameliorated the clinical and histopathological severity of induced colonic inflammation and also restored the injured gastrointestinal mucosal tissues. In conclusion, IGFBP7 contributes significantly to MSC-mediated immune modulation, as is shown by the ability of IGFBP7 knockdown in MSCs to restore proliferation and cytokine production in T-cells. These results suggest that IGFBP7 may act as a novel MSC-secreted immunomodulatory factor.