Human endometrial stem cells (EnSCs) have the potential to be ‘off the shelf’ clinical reagents for the treatment of heart failure. Here, using an immunocompetent rat model of myocardial infarction ...(MI), we provide evidence that the functional benefits of EnSC transplantation are principally and possibly exclusively through a paracrine effect. Human EnSCs were delivered by intramyocardial injection into rats 30 min. after coronary ligation. EnSC therapy significantly preserved viable myocardium in the infarct zone and improved cardiac function at 28 days. Despite increased viable myocardium and vascular density, there was scant evidence of differentiation of EnSCs into any cardiovascular cell type. Cultured human EnSCs expressed a distinctive profile of cytokines that enhanced the survival, proliferation and function of endothelial cells in vitro. When injected into the peri‐infarct zone, human EnSCs activated AKT, ERK1/2 and STAT3 and inhibited the p38 signalling pathway. EnSC therapy decreased apoptosis and promoted cell proliferation and c‐kit+ cell recruitment in vivo. Myocardial protection and enhanced post‐infarction regeneration by EnSCs is mediated primarily by paracrine effects conferred by secreted cytokines that activate survival pathways and recruit endogenous progenitor stem cells. Menstrual blood provides a potentially limitless source of biologically competent ‘off the shelf’ EnSCs for allogeneic myocardial regenerative medicine.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper studies the distributed bipartite output formation control problem of heterogeneous discrete-time linear multi-agent systems (MASs) via cooperative output regulation theory. To construct ...the bipartite formation, under the structurally-balanced augmented directed signed graph, the followers of two antagonistic subgroups are supposed to respectively keep the desired relative positions with the leader, also called as the exosystem, in the same magnitude but the opposite sign. Since the information of exosystem can not be directly obtained by all followers, the distributed exosystem observer based on the discrete-time algebraic Riccati equality (ARE) is presented and the distributed state feedback controller is further designed. Moreover, consider the case where the states of followers are not available, the distributed output feedback controller is proposed by introducing the state estimator. Finally, two numerical examples are given to demonstrate the effectiveness of analytic results.
Prehypertension is a common condition, but the extent to which it increases the risk for coronary heart disease (CHD) is unclear. The aim of this study was to determine the association between ...baseline prehypertension and risk for CHD by performing a meta-analysis of prospective cohort studies. A systematic search of published research was conducted through January 2013, using electronic databases and bibliographies of retrieved reports. Studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs) of CHD with respect to prehypertension. A random-effects model was used to combine the study-specific risk estimates. Eighteen studies, consisting of 934,106 participants and 14,952 cases, with a median follow-up period of 8.8 years, were included. Prehypertension was associated with a significantly elevated risk for CHD (RR 1.36, 95% CI 1.22 to 1.53). Eight studies consisting of 12 cohorts further provided risk estimates for low-range prehypertension (120/80 to 129/84 mm Hg) and high-range prehypertension (130/85 to 139/89 mm Hg) separately. The risk for CHD increased significantly in high-range prehypertensive populations (RR 1.53, 95% CI 1.19 to 1.97) but not in low-range prehypertensive populations (RR 1.16, 95% CI 0.96 to 1.42). In conclusion, prehypertension is associated with a significantly increased risk for developing CHD, particularly high-range prehypertension. Further well-designed randomized controlled trials are needed to clarify the efficacy of blood pressure reduction in subjects with prehypertension.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Toll‐like receptors transduce their signals through the adaptor molecule MyD88 and members of the IL‐1R‐associated kinase family (IRAK‐1, 2, M and 4). IRAK‐1 and IRAK‐2, known to form Myddosomes with ...MyD88–IRAK‐4, mediate TLR7‐induced TAK1‐dependent NFκB activation. IRAK‐M was previously known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signalling. However, we now found that IRAK‐M was also able to interact with MyD88–IRAK‐4 to form IRAK‐M Myddosome to mediate TLR7‐induced MEKK3‐dependent second wave NFκB activation, which is uncoupled from post‐transcriptional regulation. As a result, the IRAK‐M‐dependent pathway only induced expression of genes that are not regulated at the post‐transcriptional levels (including inhibitory molecules SOCS1, SHIP1, A20 and IκBα), exerting an overall inhibitory effect on inflammatory response. On the other hand, through interaction with IRAK‐2, IRAK‐M inhibited TLR7‐mediated production of cytokines and chemokines at translational levels. Taken together, IRAK‐M mediates TLR7‐induced MEKK3‐dependent second wave NFκB activation to produce inhibitory molecules as a negative feedback for the pathway, while exerting inhibitory effect on translational control of cytokines and chemokines.
IRAK‐M was reported to inhibit TLR signalling. Now, IRAK‐M is shown to activate NFκB via interaction with MyD88/IRAK‐4 leading to the induction of a negative feedback loop that limits the inflammatory response.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, ...SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.
This paper deals with the delay-dependent stability analysis problem for neural network with a time-varying delay. A proper Lyapunov-Krasovskii functional (LKF) is established by revealing the ...features of the improved Jensen integral inequality and considering two complementary integral couples with more cross information. Based on the improved Jensen inequality, a generalized integral inequality involving more free matrices is developed. With the help of the new LKF and integral inequality, some improved stability conditions with less conservatism are derived in terms of linear matrix inequality (LMI). The efficiency of theoretical results is verified by three typical numerical examples.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this paper, the synchronization stability problem for a class of general complex dynamical networks with interval time-varying coupling delay and delay in the dynamical node is investigated. By ...dividing the delay interval into two variable subintervals, slightly different Lyapunov–Krasovskii functionals are constructed on these two subintervals. Then several less conservative delay-dependent synchronization stability criteria are derived in terms of linear matrix inequality via reciprocally convex approach, which can be easily solved by using the standard numerical software. Numerical examples are given to illustrate the effectiveness and less conservatism of the proposed method.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives
This study sought to compare the efficacy and clinical safety of the LONGTY drug‐coated balloon (DCB) with those of SeQuent Please DCB in patients with in‐stent restenosis (ISR).
...Background
Although DCB technologies have evolved, little is known about the clinical efficacy of the new‐generation LONGTY DCB.
Methods
This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow‐up.
Results
A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow‐up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority <.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow‐up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups.
Conclusions
In this multicenter, head‐to‐head, randomized trial, the new‐generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcεR1. In addition to mast cells, many cell types implicated in atherogenesis ...express FcεR1, but whether IgE has a role in this disease has not been determined. Here, we demonstrate that serum IgE levels are elevated in patients with myocardial infarction or unstable angina pectoris. We found that IgE and the FcεR1 subunit FcεR1α were present in human atherosclerotic lesions and that they localized particularly to macrophage-rich areas. In mice, absence of FcεR1α reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcεR1 activity. IgE stimulated the interaction between FcεR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcεR1 or TLR4. Furthermore, IgE activated macrophages by enhancing Na+/H+ exchanger 1 (NHE1) activity. Inactivation of NHE1 blocked IgE-induced macrophage production of inflammatory molecules and apoptosis. Cultured human aortic SMCs (HuSMCs) and ECs also exhibited IgE-induced signal transduction, cytokine expression, and apoptosis. In human atherosclerotic lesions, SMCs and ECs colocalized with IgE and TUNEL staining. This study reveals what we believe to be several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases.
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