Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis.

CONTEXT: Concanavalin A (Con A) exhibited multiple roles in cancer cells. However, the role of Con A in endothelial cells was not reported. OBJECTIVE: Our present study investigated the potential angiogenic role of Con A in endothelial cells and ischaemic hind-limb mice. MATERIALS AND METHODS: Human umbilical vein endothelial cells and Ea.hy926 cells were employed to determine the effect of Con A (0.3, 1, and 3 µg/mL) or vehicle on angiogenesis and cell proliferation with tube formation, ELISA, flow cytometry, EdU, and western blot. Hind-limb ischaemic mice were conducted to determine the pro-angiogenic effect of Con A (10 mg/kg) for 7 days. RESULTS: Con A promoted tube formation to about three-fold higher than the control group and increased the secretion of VEGFa, PDGFaa, and bFGF in the medium. The cell viability was promoted to 1.3-fold by Con A 3 µg/mL, and cell cycle progression of G0G1 phase was decreased from 77% in the vehicle group to 70% in Con A 3 µg/mL, G2M was promoted from 15 to 19%, and S-phase was from 7 to 10%. Con A significantly stimulated phosphorylation of Akt and ERK1/2 and expression of cyclin D1 and decreased the expression of p27. These effects of Con A were antagonised by the PI3K inhibitor LY294002 (10 µM) and MEK pathway antagonist PD98059 (10 µM). Moreover, Con A (10 mg/kg) exhibited a repair effect in ischaemic hind-limb mice. DISCUSSION AND CONCLUSIONS: This study will provide a new option for treating ischaemic disease by local injection with Con A.

Ubiquitinated ligation protein NEDD4L participates in MiR-30a-5p attenuated atherosclerosis by regulating macrophage polarization and lipid metabolism.

MiR-30a-5p plays an important role in various cardiovascular diseases, but its effect in atherosclerosis has not been reported. Apolipoprotein E-deficient (Apo E-/-) mice were used to investigate the role of miR-30a-5p in atherosclerosis, and the underlying mechanism was investigated in vivo and in vitro. The fluorescence in situ hybridization test revealed that miR-30a-5p was expressed in Apo E-/- mice lesions. Nevertheless, in RAW264.7 macrophages, the expression of miR-30a-5p was reduced by lipopolysaccharide (LPS) or oxidized low-density lipoprotein. MiR-30a-5p-ago-treated Apo E-/- mice significantly reduced lesion areas in the aorta and aortic root, reduced levels of lipoprotein and pro-inflammatory cytokines, and increased levels of anti-inflammatory cytokines. The ratio of M1/M2 macrophages was decreased in miR-30a-5p-ago-treated Apo E-/- mice and LPS-treated RAW264.7 macrophages by the regulation of Smad-1/2 phosphorylation. MiR-30a-5p reduced lipid uptake in oxidized low-density lipoprotein-treated macrophages by regulating the expression of PPAR-γ, ABCA1, ABCG1, LDLR, and PCSK9. Ubiquitinated ligase NEDD4L was identified as a target of miR-30a-5p. Interestingly, knockdown of NEDD4L decreased the M1/M2 ratio and oxidized low-density lipoprotein uptake in macrophages by inhibiting the ubiquitination of PPAR-γ and phosphorylation of Smad-1/2 and regulating ABCA1, ABCG1, LDLR, and PCSK9. We demonstrated a novel effect and mechanism of miR-30a-5p in atherosclerosis.

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy.

BACKGROUND: Previous studies have demonstrated that human cardiac c-Kit+ progenitor cells (hCPCs) can effectively improve ischemic heart disease. However, the major challenge in applying hCPCs to clinical therapy is the low survival rate of graft hCPCs in the host heart, which limited the benefit of transplanted hCPCs. Bradykinin (BK) is a principal active agent of the tissue kinin-kallikrein system. Our previous studies have highlighted that BK mediated the growth and migration of CPCs by regulating Ca2+ influx. However, the protective effect of BK on CPCs, improvement in the survival rate of BK-pretreated hCPCs in the infarcted heart, and the related mechanism remain elusive. METHODS: HCPCs were treated with H2O2 to induce cell apoptosis and autophagy, and different concentration of BK was applied to rescue the H2O2-induced injury detected by MTT assay, TUNEL staining, flow cytometry, western blotting, and mitoSOX assays. The role of autophagy in the anti-apoptotic effect of BK was chemically activated or inhibited using the autophagy inducer, rapamycin, or the inhibitor, 3-methyladenine (3-MA). To explore the protective effect of BK on hCPCs, 3-MA or BK-pretreated hCPCs were transplanted into the myocardial infarcted rats. An echocardiogram was used to determine cardiac function, H&E and Masson staining were employed to assess pathological characteristics, HLA gene expression was quantified by qRT-PCR, and immunostaining was applied to examine neovascularization using confocal microscopy. RESULTS: The in vitro results showed that BK suppressed H2O2-induced hCPCs apoptosis and ROS production in a concentration-dependent manner by promoting pAkt and Bcl-2 expression and reducing cleaved caspase 3 and Bax expression. Moreover, BK restrained the H2O2-induced cell autophagy by decreasing LC3II/I, Beclin1, and ATG5 expression and increasing P62 expression. In the in vivo experiment, the transplanted BK- or 3-MA-treated hCPCs were found to be more effectively improved cardiac function by decreasing cardiomyocyte apoptosis, inflammatory infiltration, and myocardial fibrosis, and promoting neovascularization in the infarcted heart, compared to untreated-hCPCs or c-kit- cardiomyocytes (CPC- cells). CONCLUSIONS: Our present study established a new method to rescue transplanted hCPCs in the infarcted cardiac area via regulating cell apoptosis and autophagy of hCPCs by pretreatment with BK, providing a new therapeutic option for heart failure.

Circulating miRNA-302 family members as potential biomarkers for the diagnosis of acute heart failure.

AIM: To explore circulating miRNA-302 family members for acute heart failure (AHF) diagnosis. METHODS: Three groups of subjects, in other words, AHF patients, AHF free patients and healthy controls were recruited. Circulating levels of miR-302 family members were measured and analyzed for AHF diagnosis. RESULTS: Plasma miR-302s except miR-302f were significantly elevated in AHF patients. MiR-302b-3p had the highest area under curve value of 0.87. There were strong positive correlations between miR-302s and NT-proBNP levels. MiR-302b-3p levels were significantly higher in left ventricular ejection fraction ≤45% and New York Heart Association class IV patients compared with left ventricular ejection fraction >45% and New York Heart Association class II patients, respectively. CONCLUSION: Levels of circulating miR-302s, miR-302b-3p in particular, could be potentially applied for AHF diagnosis and the differentiation of disease severity.

Tape-Based Photodetector: Transfer Process and Persistent Photoconductivity.

We report a facile transfer method to fabricate flexible photodetectors directly on tape, wherein the films formed by different processes were integrated together. The tape-based photodetectors with CdS nanowire (NW) active layers exhibited good performances as those fabricated by conventional processes. The obvious persistent photocurrent in our device was eliminated by introducing a conductive polymer poly(3,4-ethylenedioxythiophene)polystyrene sulfonate (PEDOT:PSS) onto the CdS NW layer. By adjusting the concentration of the PEDOT:PSS aqueous solution, a device with a fast response, ultrashort decay time, and relatively large photocurrent was obtained. The decay times were 11.59 and 6.64 ms for devices using electrodes of silver NWs and gold, respectively. These values are much shorter than the shortest decay times (on the order of hundreds of milliseconds) reported previously.

Micro-tensile bond strength to sclerotic dentin in non-carious cervical lesions / 中华口腔医学杂志

<p><b>OBJECTIVE</b>This in vitro study was to evaluate the micro-tensile bond strength (microTBS) of three adhesives to sclerotic dentin in non-carious cervical lesions.</p><p><b>METHODS</b>The maxillary premolars extracted due to periodontitis and with non-carious cervical lesions were collected. The non-carious, natural cervical sclerotic lesions were bonded with a total-etching adhesive Scotchbond Multi-Purpose, a two-step self-etching adhesive Contax, and an all-in-one self-etching adhesive Adper Prompt L-Pop. Artificially prepared wedge-shaped lesions were also made in sound premolars and bonded with the same adhesives as the controls. MicroTBS of these three adhesives was measured.</p><p><b>RESULTS</b>MicroTBS of Scotchbond and Contax to sclerotic dentin was significantly lower than to normal dentin. But microTBS of Adper Prompt L-Pop to normal dentin was significantly lower than to sclerotic dentin. MicroTBS to sclerotic dentin was Scotchbond 46.805 MPa, Adper Prompt L-Pop 39.045 MPa, and Contax 29.852 MPa.</p><p><b>CONCLUSIONS</b>In sclerotic dentin the microTBS was decreased because of the inferior micro-morphology of resin tags. Adhesives with low pH value might bond to sclerotic dentin effectively.</p>

Ultrastructural study of a self-etching adhesive to sclerotic dentin in non-carious cervical lesions / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To examine, in vitro study, the ultrastructure of resin-infiltrated sclerotic dentine following the application of a two-step self-etching dentin adhesive.</p><p><b>METHODS</b>Non-carious, natural cervical sclerotic lesions were bonded using Contax (DMG Hamburg, Germany), a self-etching dentin adhesive. Artificially prepared wedge-shaped lesions were also made in sound bicuspids and bonded using the same adhesive as controls. By SEM examination, the morphological change of the dentin surface treated by Contax Primer, and the hybrid layer and resin tag in the dentin-resin interface were studied.</p><p><b>RESULTS</b>Most dentinal tubules were occluded by rod-like sclerotic casts in the sclerotic dentin surface. Both hybrid layer and resin tag were observed in sclerotic dentin. The hybrid layer was almost similar to that in the sound dentin, but the resin tags were shorter than those in controls.</p><p><b>CONCLUSIONS</b>Bonding to sclerotic dentin is different from sound dentin and may be compromised by occluded dentin tubules. Based on the present ultrastructural features of hybrid layer and resin tags, the Contax, a self-etching dentin adhesive with a low pH value primer, may have some bonding efficacy to sclerotic dentin.</p>