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The DNA damage response (DDR) plays crucial roles in cancer prevention and therapy. Poly(ADP-ribose) polymerase 1 (PARP1) mediates multiple signal transduction in the DDR as a master regulator. Uncovering the regulatory factors of PARP1 contributes to a more comprehensive view of tumorigenesis and treatment strategies. Here, we reveal that MARVELD1 acts as a mediator of DDR to perform early events and maintain genome stability. Mechanistically, PARP1 PARylates MARVELD1 at D102, D118 and D130, and in turn, MARVELD1 stabilizes PARP1 by enhancing NAA50-mediated acetylation, thus forming a positive feedback loop. MARVELD1 knockout mice and their embryo fibroblasts exhibit genomic instability and shorter half-life of PARP1. Moreover, MARVELD1 partnering with PARP1 facilitates resistance to genotoxic drugs and disrupts PARP inhibitor (PARPi) effect in PDX model of colorectal cancer (CRC). Overall, our results underline the link between MARVELD1 and PARP1 in therapeutic resistance based on DDR and provide new insights for clinical tumor therapy of PARPi.

The aim of this study was to investigate the role of RKHog1 in the cold adaptation of Rhodosporidium kratochvilovae strain YM25235 and elucidate the correlation of biosynthesis of polyunsaturated fatty acids (PUFAs) and glycerol with its cold adaptation. The YM25235 strain was subjected to salt, osmotic, and cold stress tolerance analyses. mRNA levels of RKhog1, Δ

Neodymium oxide nanoparticles (NPs-Nd

MiRNA expression was determined in both proliferating and differentiated cardiac stem cells (CSCs) through a comprehensive miRNA microarray analysis. We selected miR218 for functional follow-up studies to examine its significance in CSCs. First, we observed that the expression of miR218 was altered in CSCs during differentiation into cardiomyocytes, and transfection of an miR218 mimic or miR218 inhibitor affected the myocardial differentiation of CSCs. Furthermore, we observed that a negative regulator of Wnt signaling, sFRP2, was a direct target of miR218, and the protein levels of sFRP2 were increased in cells transfected with the synthetic miR218 inhibitor. In contrast, transfection with the miR218 mimic decreased the expression of sFRP2 and potentiated Wnt signaling. The subsequent down-regulation of sFRP2 by shRNA potentiated Wnt signaling, contributing to a gene expression program that is important for CSC proliferation and cardiac differentiation. Specifically, canonical Wnt signaling induced miR218 transcription. Thus, miR218 and Wnt signaling were coupled through a feed-forward positive feedback loop, forming a biological regulatory circuit. Together, these results provide the first evidence that miR218 plays an important role in CSC proliferation and differentiation through the canonical Wnt signaling pathway.

Introduction Mesenchymal stem cell (MSC)-based therapies have demonstrated positive outcomes for treating cardiovascular disease. However, the proliferative ability of MSCs decreases during chronic exposure to hyperglycaemia; their ability to contribute to endogenous injury repair is thus reduced. Erythropoietin (EPO) was recently reported to protect against hyperglycaemia-related injury in various cells and may be a good candidate for enhancing MSC functions under hyperglycaemic conditions. Methods Bone marrow-derived MSCs were isolated from male donor rats weighing 60–80 g. The roles of EPO in regulating cell viability, senescence, angiogenesis and inflammation were investigated using the Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) assays; senescence-associated β-galactosidase (SA-β-gal) staining; VEGF, HGF, IGF, bFGF ELISAs and TNF-α ELISA, respectively. ROS production was measured by flow cytometry. The expression levels of Akt, forkhead box class O3a (FoxO3a) and VEGF proteins in MSCs were analysed by western blotting. Matrigel was used for tube formation assays. Results The results of the current study showed that EPO has beneficial effects on MSCs exposed to hyperglycaemia by promoting proliferation, inhibiting senescence and the release of pro-inflammatory factors, increasing the secretion of proangiogenic cytokines, and enhancing the ability of MSCs to stimulate tube formation among human umbilical vein endothelial cells (HUVECs). In addition, the beneficial effects of EPO may result from the activation of the Akt/FoxO3a signalling pathway. Conclusions Our study demonstrates for the first time that EPO protects MSCs from hyperglycaemia-induced damage by targeting the Akt/FoxO3a signalling pathway.

Background: Multiple atrial tachycardias (ATs) in one patient usually require more complex ablation procedures. Despite the superior accuracy and understanding of conduction features provided by high-resolution mapping, Multiple ATs are still associated with high recurrence rates, and other mechanisms may play a role. Therefore, we aimed to uncover the substrates maintaining these multiple reentrant circuits and the probable mechanisms for the high occurrence of arrhythmia. Methods: Mapping via the Carto system was carried out in 8 patients with more than two types of reentrant circuits during ablation. Functional conduction block (FCB) regions were marked and further analyzed. Results: Twenty sustained ATs were mapped in the 8 patients. Five of these patients exhibited a potential FCB region that changed between different ATs. The potentials of these regions converted between double potentials (DPs), fractionated potentials (FPs) and normal potential due to the different ATs. The FCB regions were the main obstacles and the center of the reentrant circuit in 8 of 14 ATs, and in the other ATs, these regions played a role in reorganizing the conduction pathway. In the activation mapping, the FCB areas were never the target ablation site. Conclusion: The potential FCB region is common in ATs with more than two types of reentrant circuits, especially in scar-related localized reentry. The convertibility of FCB regions provide one of the critical substrates in maintaining multiple ATs. The changefulness of this substrate may be one of the important causes of the high recurrence of related ATs

Background Erythropoietin (EPO), which is clinically used for renal anaemia, reportedly exerts beneficial pleiotropic effects in atherosclerosis. This aim of this study was to investigate the effects of EPO on macrophage inflammation and polarization under hyperglycaemic conditions and to identify the effects of EPO-treated macrophage supernatants (SNs) on endothelial cell (EC) function. Methods Peritoneal macrophages (pMΦs) were isolated from normal, diabetic or EPO-injected mice. Pro-inflammatory factors were detected by qRT-PCR and ELISA, and macrophage phenotype markers were evaluated by flow cytometry. High glucose culture was used to mimic the hyperglycaemic microenvironment of diabetes mellitus (DM) in vitro . After exposure to various doses of stimuli, macrophage inflammation and phenotype were detected via ELISA, qRT-PCR and flow cytometry. The underlying mechanism was investigated through western blotting. To examine the communication between macrophages and ECs, ECs were cultured with the SN of macrophages treated with different stimuli, and the tube formation ability of ECs was detected using Matrigel. The VEGF, ICAM-1 and VCAM-1 protein expression levels were determined by western blotting, and the nitric oxide (NO) and endothelin-1 (ET-1) expression levels were measured with a nitric oxide indicator and by ELISA, respectively. Results EPO treatment increased the M2 macrophage population and decreased the number of M1 macrophages. EPO decreased the secretion of pro-inflammatory factors, including TNF-α, iNOS and IL-6. The JAK2/STAT3 signalling pathway was also identified as being involved in the M1 macrophage transition. The SN of macrophages treated with EPO (SN-EPO) presented increased NO and ET-1 levels and decreased ICAM-1 and VCAM-1 levels. Tube formation assays revealed that the SN-EPO promoted the ability of ECs to form capillary-like structures in vitro . In contrast, AZD1480, a JAK2 inhibitor, abolished this SN-EPO effect. Conclusion EPO treatment alleviated the inflammatory reaction in DM mice and inhibited M1 polarization through the JAK2/STAT3 pathway. Moreover, EPO treatment promoted the tube formation ability of ECs in a VEGF-dependent manner and decreased the production of adhesion molecules, a vasodilator and a vasoconstrictor.

Plaque vulnerability indicates the risk of a cardiovascular event. In the present study, we sought to analyze the relationship between trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, and vulnerable plaque characteristics in patients with coronary artery disease (CAD).One hundred eighty non-culprit plaques from 90 patients with ACS or with stable angina were assessed by optical coherence tomography (OCT). The plasma TMAO levels were measured using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-QTOF/MS).Patients were divided into two groups (high TMAO group and low TMAO group) according to the median plasma TMAO level (114.73 μg/L). The non-culprit plaques in the high TMAO group exhibited a thinner fibrous cap thickness (FCT) (65.97 ± 25.89 vs. 93.0 ± 28.28 μm, P 0.001), higher frequency of microvessels (75.6% vs. 31.1%, P 0.001, per-patient) and increased incidence of thin-cap fibroatheroma (TCFA) (69.2% vs. 18.4%, P 0.001, per-patient) compared with the low TMAO group. Moreover, the level of TMAO was negatively associated with FCT (r = -0.418, P 0.001). Furthermore, multivariate regression analysis results showed that TMAO (OR: 7.455, 95% CI: 2.753-20.189, P 0.001) had a significant association with TCFA, with a cut-off point of 118.34 μg/L, specificity of 72.6% and sensitivity of 79.5% in predicting the prevalence of TCFA.In conclusion, these findings suggest that the level of TMAO is significantly correlated with the incidence of TCFA. New biomarkers acquired through non-invasive means, such as TMAO, offer the potential to improve risk stratification and clinical management in patients with CAD.

As an integral part of the Earth's climate system, the Kuroshio Current (KC) plays a crucial role in shaping the regional oceanography and climate in the Northern Hemisphere. However, how the KC dynamics have varied over glacial-interglacial cycles is still under debate. The dynamic transfer and accumulation of submarine hydrothermal source materials by deep-reaching KC offer us a unique opportunity to examine the variations in dynamics of the KC. Here, we used novel proxies of sedimentary mercury (Hg) and antimony (Sb) in core MD01-2404 retrieved from the middle Okinawa Trough (OT) to reconstruct the evolution of the KC hydrodynamics over the last 92,000 years. We infer the enrichments of sedimentary Hg and Sb to signify hydrothermal input, which is delivered laterally to the study site by deep circulation in association with the KC, thus indicating the dynamics of KC. Overall, both the sedimentary Hg and Sb in core MD01-2404 indicate a persistent influence on the KC dynamics within the OT over the last glacial-interglacial cycles. Furthermore, our Hg and Sb proxies suggest a significantly weakened influence during the last deglaciation and last glacial period while a strengthened influence during the Holocene and late Marine Isotope Stage 5. Our studies imply that the orbital-scale dynamics of KC are controlled by tropical atmosphere-ocean interactions induced by sea surface temperature changes and regulated by the extratropical climate conditions.

Background The mechanism of cholesteryl ester transfer protein (CETP) in lipid metabolism is still unclear. Furthermore, the relationship of CETP and atherosclerosis (AS) has been controversial. As pigs are a good model for both lipid and AS research, we investigated the lipid metabolism of human CETP (hCETP) transgenic pigs and explored the mechanism of CETP in lipid modulation. Methods Plasmids expressing the hCETP gene were designed, successfully constructed, and transfected into porcine fetal fibroblasts by liposomes. Using somatic cell nuclear transfer technology and embryonic transfer, hCETP transgenic pigs were generated. After the DNA, RNA, and protein levels were identified, positive hCETP transgenic pigs were selected. Blood samples were collected at different ages to evaluate the phenotypes of biochemical markers, and the metabolomes of plasma samples were analyzed by liquid mass spectrometry. Results Eight positive hCETP transgenic pigs and five negative cloned pigs were generated by transgenic technology. Finally, five hCETP transgenic and five cloned pigs were grown healthily. After feeding with a normal diet, hCETP transgenic pigs compared with unmodified pigs had no significant differences in body weight, liver function, kidney function, or plasma ions, while total cholesterol and low-density lipoprotein were higher than in unmodified pigs, and high-density lipoprotein was significantly decreased. Metabolomics analysis showed that there were differences in metabolic components between hCETP transgenic pigs, cloned pigs, and unmodified pigs. Conclusions In this study, we created hCETP transgenic pigs that could serve as an excellent model for lipid disorders and atherosclerosis. Electronic supplementary material The online version of this article (10.1186/s12944-017-0563-x) contains supplementary material, which is available to authorized users.

The increasing wall stress as is elicited by arterial hypertension promotes their reorganization in the vessel wall which may lead to arterial stiffening and contractile dysfunction. The nuclear factor of activated T cells 5 (NFAT5) pathway plays a role in regulating growth and differentiation in various cell types. We investigated whether the NFAT5 pathway was involved in the regulation of biomechanical stretch-induced human arterial smooth muscle cell (HUASMC) proliferation, inflammation, and migration. Herein, we showed that stretch promoted the expression of NFAT5 in human arterial smooth muscle cells and regulated through activation of c-Jun N-terminal kinase under these conditions. This may contribute to an improved activity of HUASMCs and thus promote reorganization in vascular remodeling processes such as hypertension-induced arterial stiffening and contractile dysfunction.

Nicorandil, a drug with both nitrate-like and ATP-sensitive potassium (KATP) channel-activating properties, has been well demonstrated in various aspects of myocardial infarction (MI), especially in inhibiting cell apoptosis and increasing coronary flow. However, the role of nicorandil in regulating inflammation and angiogenesis following myocardial infarction is still unrevealed. In the present study, we explored the effect of nicorandil on macrophage phenotype transition and inflammation regulation and the potential underlying mechanisms. For the phenotype transition and phagocytosis ability of macrophages detection, flow cytometry analysis was used. The inflammation factors were measured with ELISA and qRT-PCR. Western blot was used to assess the levels of NF-κb and its target genes and VEGF expression. The tube formation ability of endothelial cells was examined on matrigel. We discovered that nicorandil can obviously inhibit the differentiation of monocytes into mature macrophages and decrease M1 phenotype transition both in peritoneal macrophages and cultured macrophage cell line in normal or hypoxia and serum deprivation (H/SD) conditions. Meanwhile, nicorandil can induce an anti-inflammatory M2 phenotype. Thereby, nicorandil regulated macrophages switching to M1/M2 status. Our data further showed that NF-κb and the expression of its target genes were pivotal players in the regulation of macrophages phenotype. Besides, we also showed that nicorandil can promote the tube formation and VEGF expression in endothelial cells. We concluded that nicorandil may serve as an effective modulator of NF-κb signaling pathway during the pathogenesis of MI via regulating M1/M2 status and promoting angiogenesis.

Aims Endothelial progenitor cell (EPC) dysfunction underlies a critical risk factor in diabetic vascular complications due to function defect in restoring endothelium injury. Crocetin has attracted increasing attention in several vascular-related diseases. In present study, we aimed to explore the role of crocetin in diabetic EPC dysfunction. Main methods EPCs were isolated from bone marrow in diabetic mice and identified using the fluorescence staining and flow cytometry. After exposure to various doses of crocetin, cell viability was detected by MTT assy. Then, colony formation, lactate dehydrogenase (LDH) release, cell apoptosis and caspase-3 activity were assessed. The underlying mechanism was also investigated by western blotting. Key findings EPCs from diabetic mice exhibited dysfunction under hyperglycemia condition. Interestingly, crocetin treatment alleviated the impairment in diabetic EPC proliferation and colony formation. Simultaneously, the increases in LDH release, cell apoptosis and caspase-3 activity were also restrained following crocetin stimulation. Additionally, EPC migration response to SDF-1 was also impaired under diabetic condition, which was partly restored by crocetin. Mechanism analysis manifested that administration with crocetin repaired the damage in the activation of PI3K/AKT-eNOS pathway and NO production, but attenuated ROS elevation in diabetic EPCs. Importantly, preconditioning with antagonist of LY294002 (for PI3K/AKT) or N G -monomethyl- l -arginine (for eNOS) antagonized the beneficial effect of crocetin on diabetic EPC dysfunction. Significance These data corroborated that crocetin could restore the dysfunction of diabetic EPCs by enhancing NO bioavailability via regulation of PI3K/AKT-eNOS and ROS pathways. Therefore, this research supports a potential promising therapeutic aspect for diabetic patients.

Cardiac stem cells (CSCs) are the most promising and effective candidates for the therapy of cardiac regenerative diseases; however, they have marked limitations. For instance, the implantation of CSCs is hampered by factors such as their sustainability and long-term durability. Gene modification appears to be the most effective method of optimizing CSCs and gene therapy trials have demonstrated that efficient gene transfer is key to achieving therapeutic efficacy. However, the transduction ability of adenovirus (Ad) is limited. Previous studies have reported that low expression of coxsackie and adenovirus receptor (CAR) in target cells decreases the transduction efficiency. A promising method for improving Ad-mediated gene transfer is to increase CAR expression in target cells. The present study investigated the effect of the Raf-mitogen-associated protein kinase (MAPK) kinase (MEK)-extracellular signal-associated protein kinase (ERK) signaling pathway on the expression of CAR on CSCs, as this pathway decreases cell-cell adhesion via cell surface molecules. The results demonstrated that interference with the Raf-MEK-ERK signaling pathway by knockdown of ERK1/2 upregulated the expression of CAR. The entry of the Ad into the cells was increased following inhibition of ERK1/2. Moreover, following knockdown of CAR, the entry of Ad into cells was decreased. However, knockdown of c-Jun N-terminal kinase and p38 as other components of the MAPK pathway did not affect CAR expression. Therefore, CAR expression in CSCs may be mediated via the Raf-MEK-ERK signaling pathway. Upregulation of CAR by knockdown of ERK1/2 may significantly improve Ad-mediated genetic modification of CSCs in the treatment of cardiovascular diseases.

Cables1 (Cdk5 and Abl enzyme substrate 1) is a vital cell cycle regulator and a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Here, we report on the critical role of the Cables1/p21 pathway, which inhibits cell proliferation and induces cell senescence in human umbilical vein endothelial cells. Moreover, we confirmed that silencing of Cables1 promoted cell proliferation as well as increased resistance to angiotensin II-induced senescence, at least in part, by altering Cables1 activation. We further demonstrated that knockdown of p21 reverses Cables1-mediated cell growth inhibition and cell senescence. Taken together, these results suggest that the Cables1/p21 pathway has a strong effect on the induction of cell senescence and inhibition of cell growth, and acts as a novel regulatory mechanism in which p21 is probably one of several downstream effector molecules to mediate Cables1.

After the publication of our article, we became aware that there were errors in Fig. 3c and 3d were incorrectly presented.

Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality in diabetic patients. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been reported to be effective in protecting the heart against ROS accumulation during the development of DCM. We hypothesize that the AMPK/PGC-1α axis may play a crucial role in exercise-induced bioenergetic metabolism and aerobic respiration on oxidative stress parameters in the development of diabetic cardiomyopathy. Using a streptozotocin/high-fat diet mouse to generate a diabetic model, our aim was to evaluate the effects of exercise on the cardiac function, mitochondrial oxidative capacity, mitochondrial function, and cardiac expression of PGC-1α. Mice fed a high-fat diet were given MO-siPGC-1α or treated with AMPK inhibitor. Mitochondrial structure and effects of switching between the Warburg effect and aerobic respiration were analysed. Exercise improved blood pressure and systolic dysfunction in diabetic mouse hearts. The beneficial effects of exercise were also observed in a mitochondrial function study, as reflected by an enhanced oxidative phosphorylation level, increased membrane potential, and decreased ROS level and oxygen consumption. On the other hand, depletion of PGC-1α attenuated the effects of exercise on the enhancement of mitochondrial function. In addition, PGC-1α may be responsible for reversing the Warburg effect to aerobic respiration, thus enhancing mitochondrial metabolism and energy homoeostasis. In this study, we demonstrate the protective effects of exercise on shifting energy metabolism from fatty acid oxidation to glucose oxidation in an established diabetic stage. These data suggest that exercise is effective at ameliorating diabetic cardiomyopathy by improving mitochondrial function and reducing metabolic disturbances.

The environmental-friendly scale and corrosion inhibitors have been a hot topic in research. Four carboxylic acid type scale and corrosion inhibitors are introduced in this study, including polyaspartic acid (PASP), polyepoxysuccinic acid (PESA), oxidized starch (OS), and carboxymethyl cellulose (CMC). The scale and corrosion inhibition performance of PASP, PESA, OS, and CMC were investigated by molecular dynamics (MD) simulation and density functional theory (DFT) calculation. The interaction between the inhibitor and the surface of CaCO3 (1 1 0), CaCO3 (1 0 4), CaSO4 (0 2 0), and Fe (1 1 0) was explored with and without water, respectively. The results indicate that the binding energy of the inhibitor onto the surface of CaCO3 (1 1 0), CaCO3 (1 0 4), and CaSO4 (0 2 0) is as follows: PESA > PASP > OS > CMC. The binding energy onto the Fe (1 1 0) surface is: PASP > OS > CMC > PESA. It is worth noting that the influence of water molecules cannot be ignored. Besides, the global reactivity parameters of four inhibitors were also calculated to further explain the corrosion inhibition performance and mechanism, such as EHOMO, ELUMO, ΔE, χ.

Macrophage migration inhibitory factor (MIF) has pleiotropic immune functions in a number of inflammatory diseases. Recent evidence from expression and functional studies has indicated that MIF is involved in various aspects of cardiovascular disease. In this study, we aimed to determine whether MIF supports in vitro c-kit+CD45- cardiac stem cell (CSC) survival, proliferation and differentiation into endothelial cells, as well as the possible mechanisms involved. We observed MIF receptor (CD74) expression in mouse CSCs (mCSCs) using PCR and immunofluorescence staining, and MIF secretion by mCSCs using PCR and ELISA in vitro. Increasing amounts of exogenous MIF did not affect CD74 expression, but promoted mCSC survival, proliferation and endothelial differentiation. By contrast, treatment with an MIF inhibitor (ISO-1) or siRNA targeting CD74 (CD74‑siRNA) suppressed the biological changes induced by MIF in the mCSCs. Increasing amounts of MIF increased the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which are known to support cell survival, proliferation and differentiation. These effects of MIF on the mCSCs were abolished by LY294002 [a phosphoinositide 3-kinase (PI3K) inhibitor] and MK-2206 (an Akt inhibitor). Moreover, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation increased following treatment with MIF. The AMPK inhibitor, compound C, partly blocked the pro-proliferative effects of MIF on the mCSCs. In conclusion, our results suggest that MIF promotes mCSC survival, proliferation and endothelial differentiation through the activation of the PI3K/Akt/mTOR and AMPK signaling pathways. Thus, MIF may prove to be a potential therapeutic factor in the treatment of heart failure and myocardial infarction by activating CSCs.

Mesenchymal stem cell (MSC)-based therapies have had positive outcomes both in animal models of cardiovascular diseases and in clinical patients. However, the number and function of MSCs decline during hypoxia and serum deprivation (H/SD), reducing their ability to contribute to endogenous injury repair. MicroRNA-34a (miR-34a) is originally identified as a TP53-targeted miRNA that modulates cell functions, including apoptosis, proliferation, and senescence via several signaling pathways, and hence is an appealing target for MSC-based therapy for myocardial infarction.Bone marrow-derived MSCs were isolated from 60-80 g male donor rats. Expression levels of miR-34a were determined by qRT-PCR. The roles of miR-34a in regulating cell vitality, apoptosis and senescence were investigated using the cell counting kit (CCK-8) assay, flow cytometric analysis of Annexin V-FITC/PI staining and senescence-associated β-galactosidase (SA-β-gal) staining, respectively. The expression of silent information regulator 1 (SIRT1) and forkhead box class O 3a (FOXO3a) and of apoptosis- and senescence-associated proteins in MSCs were analyzed by western blotting.The results of the current study showed that miR-34a was significantly up-regulated under H/SD conditions in MSCs, while overexpression of miR-34a was significantly associated with increased apoptosis, impaired cell vitality and aggravated senescence. Moreover, we found that the mechanism underlying the proapoptotic function of miR-34a involves activation of the SIRT1/FOXO3a pathway, mitochondrial dysfunction and finally, activation of the intrinsic apoptosis pathway. Further study showed that miR-34a can also aggravate MSC senescence, an effect which was partly abolished by the reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC).Our study demonstrates for the first time that miR-34a plays pro-apoptotic and pro-senescence roles in MSCs by targeting SIRT1. Thus, inhibition of miR-34a might have important therapeutic implications in MSC-based therapy for myocardial infarction.

High glucose-induced endothelial dysfunction is a critical initiating factor in the development of diabetic vascular complications. Omentin-1 has been regarded as a novel biomarker of endothelial function in subjects with type-2 diabetes (T2D); however, it is unclear whether omentin-1 has any direct effect in ameliorating high glucose-induced endothelial dysfunction. In the present study, we analyzed the effect of omentin-1 on high glucose-induced endothelial dysfunction in isolated mouse aortas and mouse aortic endothelial cells (MAECs). Vascular reactivity in aortas was measured using wire myography. The expression levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor δ (PPARδ), Akt, endothelial nitric-oxide synthase (eNOS), and endoplasmic reticulum (ER)-stress markers in MAECs were determined by Western blotting. The production of reactive oxygen species (ROS) and nitric oxide (NO) was assessed by diluted fluoroprobe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM DA), respectively. We found that ex vivo treatment with omentin-1 reversed impaired endothelial-dependent relaxations (EDR) in mouse aortas after high-glucose insult. Elevated ER-stress markers, oxidative stress, and reduction of NO production induced by high glucose in MAECs were reversed by omentin-1 treatment. Omentin-1 also effectively reversed tunicamycin-induced ER stress responses in MAECs, as well as ameliorated impairment of endothelial-dependent relaxation in mouse aortas. Moreover, omentin-1 increased AMPK phosphorylation with a subsequent increase in PPARδ expression, while also restoring the decreased phosphorylation of Akt and eNOS. The effects of omentin-1 were abolished by cotreatment of compound C (AMPK inhibitor) and GSK0660 (PPARδ antagonist). These data indicate that omentin-1 protects against high glucose-induced vascular-endothelial dysfunction through inhibiting ER stress and oxidative stress and increasing NO production via activation of AMPK/PPARδ pathway.

This paper considers the problem of exponential stability control for nonlinear uncertain networked control systems. Based on the T-S method, a model of nonlinear networked control systems is obtained. Corresponding to the probability of the delays taking value in different interval, a stochastic variable satisfying Bernoulli distribution is introduced and a new fuzzy networked control systems is built by employing the information of the probability distribution. With the Lyapunov stability theorem, the mean-square exponential stability conditions and the state feedback fuzzy controller design methods are given in terms of LMI. Finally, a numerical example is given to demonstrate the validity of the results.

Limited angle tomography is a severely ill-posed problem yet practically significant in x-ray computed tomography. In recent development, limited angle tomography problem is casted in the form of convex optimization problem. In this paper, incorporating anisotropic total variation with Mumford-Shah functional, we propose a novel objective functional and develop the corresponding alternating optimization algorithm. The experimental results demonstrate the efficiency of Mumford-Shah functional minimization for limited angle tomography. Furthermore, we also get the segmentations of reconstructed images.

Background MicroRNAs (miRNAs) have emerged as crucial factors that regulate proliferation and apoptosis of cardiac c-kit+ cells. Although much is known about their role in maintaining cardiac c-kit+ cell pluripotency, the mechanisms by which they affect cell fate decisions that are an essential part of the repair of heart failure remain poorly understood. Methods Cardiac c-kit+ cells were obtained from Balb/c mice and cultured in vitro. Lentiviral vectors of miR199a-3p, its corresponding anti-miRNA, or short hairpin RNA against Cables1 were transfected into cells. The proliferation of cardiac c-kit+ cells was evaluated using EdU and flow cytometry. Furthermore, we examined cell apoptosis by flow cytometry under treatment with 200nM angiotensin II for 48 h. The levels of miR199a-3p and Cables1 mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to examine the expression of Cables1 and P53 proteins. Results We demonstrated a significantly decreased expression of miR199a-3p in heart failure samples compared with healthy donors. Meanwhile, we identified miR199a-3p as a proliferation- and apoptosis-associated regulator impacted through Cdk5 and Abl enzyme substrate 1 (CABLES1) targeting, and also attributed their repression to P53 protein expression. We further demonstrated that P53 induced miR199a-3p expression and, in turn, miR199-3p decreased P53 activity. Conclusion Collectively, our findings uncover one new mechanism by which P53 induced miR199a-3p expression and, in turn, miR199-3p decreased P53 activity. Therefore, miR199a-3p and P53 are coupled through CABLES1 and comprise a novel negative feedback loop that likely contributes to cardiac c-kit+ cell proliferation and apoptosis.

Potts model, also called piecewise-constant Mumford-Shah problem, belongs to the class of L0-regularized problems. It is non-smooth, non-convex and non-deterministic polynomial hard. Based on split Bregman method, this paper presents a new algorithm for Potts model. In view of the fact that Potts model tends to form edges in several directions, the weighted Potts model is proposed for limited angle tomography problem. The experimental results demonstrate the superiority of weighted Potts model.

Introduction Limited availability of suitable animal model of plaque disruption and thrombosis has hampered the study of mechanism and preclinical evaluation of plaque-stabilizing therapies. This study aims to develop an animal model of atherosclerotic plaque disruption and thrombosis in rabbit femoral artery. Methods Silastic collars were placed around the bilateral femoral arteries of rabbits, which had been fed with atherogenic diet for 7 days. After 28 days on the same diet, the rabbits received pharmacological triggering by intraperitoneal injection of Russell's viper venom (RVV, 0.15 mg/kg) followed by intravenous injection of histamine (0.02 mg/kg), and the animals were then processed for imageological and histological examinations. Results Perivascular collar placement of the femoral artery in high-cholesterol-fed rabbits for 28 days induced marked intimal hyperplasia, which was a lipid- and collagen-rich lesion that contained substantial amount of macrophages and smooth muscle cells. Subsequent histological analysis showed that the pharmacological triggering evoked plaque disruption and platelet- and fibrin-rich thrombi in the collared femoral arteries. Conclusion We demonstrated, for the first time, a rabbit model of plaque disruption and thrombosis induced by the combination of perivascular collar placement, RVV, and histamine injections. This model can be rapidly formed, easily operated, and site controlled.

Background The purpose was to develop a rabbit model of intimal hyperplasia with controllable lesion. Methods Following 1 week of a 2% cholesterol diet, 32 New Zealand White male rabbits underwent right femoral arteries surgical perfusion with distilled water for 1, 3, 5, or 7 min (n=8/group). After a further 4 weeks of the same diet, serum total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were measured in all rabbits. Intimal hyperplasia in histological sections of arteries were assessed by intimal proliferation ratio. Macrophage numbers and levels of proteins matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2, and alpha smooth muscle actin in lesions were analyzed by immunohistochemistry. Results Serum lipids levels showed no statistical difference between experimental groups. Intimal proliferation ratio increased gradually with perfusion time, and a positive linear correlation was calculated between intimal proliferation ratio and duration of distilled water perfusion. Similarly, number of macrophages and levels of matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2, and alpha smooth muscle actin in lesions increased with perfusion time. Conclusions A novel model of intimal hyperplasia was established by intravascular distilled water perfusion in high-cholesterol-fed rabbits. Importantly, this model exhibits time-dependent neointimal proliferation lesions that can be readily controlled in terms of extent, thus providing an avenue for further studies.