Advanced Glycation End Products Downregulate Connexin 43 and Connexin 40 in Diabetic Atrial Myocytes via the AMPK Pathway.

Purpose: Diabetes mellitus is an independent risk factor for atrial fibrillation (AF), which may be related to accumulation of advanced glycation end products (AGEs). However, the mechanisms involved are not completely clear. Abnormality of gap junction proteins, especially connexin 43 (Cx43) and connexin 40 (Cx40) in atrial myocytes, is an important cause of increased susceptibility of AF. The aim of our work is to investigate the mechanism of dysregulated Cx43 and Cx40 in atrial myocytes of diabetic rats. Methods: We established a type 1 diabetic rat model by intraperitoneal injection of streptozotocin. HL-1 cells and primary rat atrial myocytes were treated with AGEs in vitro. Using Western blotting, immunofluorescence staining, immunohistochemistry, and lucifer yellow diffusion measurements, we investigated dysregulation of Cx43 and Cx40 and its mechanism in atrial myocytes of diabetic rats. Results: Accumulation of AGEs was found in diabetic rats. The expression of Cx43 and Cx40 was reduced in the atrium of diabetic rats, accompanied by the decrease of phosphorylated Adenosine 5'-monophosphate-activated protein kinase (p-AMPK). Similar results were found in cultured HL-1 cells and primary rat atrial myocytes, suggesting a role of AGEs on gap junction proteins. An AMPK agonist, 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), reversed the down-regulated Cx43 expression induced by AGEs stimulation. More importantly, lucifer yellow diffusion assay showed that AGEs significantly affected gap junctional function, and these changes were reversed by AICAR. Conclusion: Thus, we conclude that AGEs cause dysregulation of Cx43 and Cx40 in diabetic atria via the AMPK pathway, thereby leading to gap junction dysfunction, which may contribute to the increased AF susceptibility in diabetes.

Radiofrequency ablation of premature ventricular contractions guided by robotic magnetic navigation combined with pattern matching filter.

BACKGROUND: This study's intent is to evaluate the usefulness of pattern matching filter (PMF) function combined with robotic magnetic navigation (RMN) in guiding the ablation of premature ventricular contractions (PVCs). HYPOTHESIS: Assume that PMF can improve the outcomes of PVCs ablation using RMN. METHODS: A retrospective analysis was completed consisting of 118 consecutive patients with PVCs who underwent radiofrequency ablation guided by RMN. According to the application of PMF, patients were divided into two groups: 20 patients underwent ablation without PMF (group A), and another 98 patients received ablation incorporating PMF (group B). RESULTS: Compared with group A, the procedure time (135.0 ± 28.3 min vs. 106.3 ± 37.9 min, p = 0.02) in group B was significantly decreased, while the X-ray exposure time (6.0 ± 2.6 min vs. 6.5 ± 3.6 min, p = 0.705) and dose (3.2 ± 2.4 gycm2 vs. 3.9 ± 2.7 gycm2 ，p = 0.208) had no significant difference. Group B had a more than twofold number of points acquired (66.9 ± 23.0 vs. 143.9 ± 68.3, p < 0.001) and required a shorter radiofrequency ablation time (13.2 ± 3.5 min vs. 8.1 ± 2.9 min, p < 0.001). There were no serious complications in either group. The acute success rate was similar [90.0% (18/20) vs. 87.8% (86/98), p = 1.000] in two groups, and the success rate was also similar in the long-term follow-up [83.3% (15/18) vs. 87.2% (75/86), p = 0.776]. CONCLUSIONS: The ablation of PVCs guided by RMN is safe and effective. Combined with the functional capability of PMF, both procedure time and radiofrequency ablation time were significantly decreased.

Room temperature ferromagnetism and antiferromagnetism in two-dimensional iron arsenides.

The discovery of two-dimensional (2D) magnetic materials with high critical temperature and intrinsic magnetic properties has attracted significant research interest. By using swarm-intelligence structure search and first-principles calculations, we predict three 2D iron arsenide monolayers (denoted as FeAs-I, II and III) with good energetic and dynamical stabilities. We find that FeAs-I and II are ferromagnets, while FeAs-III is an antiferromagnet. FeAs-I and III have sizable magnetic anisotropy comparable to the magnetic recording materials such as the FeCo alloy. Importantly, we show that FeAs-I and III have critical temperatures of 645 K and 350 K, respectively, which are above room temperature. In addition, FeAs-I and II are metallic, while FeAs-III is semiconducting with a gap comparable to Si. For FeAs-III, there exist two pairs of 2D antiferromagnetic Dirac points below the Fermi level, and it displays a giant magneto band-structure effect. The superior magnetic and electronic properties of the FeAs monolayers make them promising candidates for spintronics applications.

Comparisons of efficacy, safety, and recurrence risk factors of paroxysmal and persistent atrial fibrillation catheter ablation using robotic magnetic navigation system.

BACKGROUND: No data exist on comparisons of efficacy, safety, and recurrence risk factors of paroxysmal and persistent atrial fibrillation (AF) ablation using robotic magnetic navigation system (MNS), respectively. METHODS: About 151 AF patients were prospectively enrolled and divided into paroxysmal AF group (n = 102) and persistent AF group (n = 49). Circumferential pulmonary vein antrum isolation (CPVI) was performed in all patients. Linear ablation at the left atrial roof and mitral isthmus was performed in patients with persistent AF in addition to CPVI. The procedural time, X-ray exposure time, acute and long-term success rates of CPVI, and procedure-related complications were analyzed. The AF recurrence rates in the two groups were compared during 1 year, and Cox regression was used to analyze the recurrence risk factors. RESULTS: The acute success rates of CPVI in the two groups were 98.04% and 97.96%, respectively. There were no significant differences in the procedural time, X-ray exposure time, and ablation time between the two groups (P > 0.05). No serious complications appeared in either group. The AF ablation success rates were 70.6% and 57.1% for the paroxysmal and persistent groups respectively at 12-month follow-up (P = 0.102). AF duration and coronary heart disease prior to ablation were associated with the higher AF recurrence in patients with persistent AF. CONCLUSION: Ablation using MNS is effective and safe both in patients with paroxysmal and persistent AF. AF duration and coronary heart disease prior to ablation are two independent risk factors of AF recurrence in patients with persistent AF postoperatively.

Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment.

BACKGROUND: Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified. METHODS: We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs. RESULTS: Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway. CONCLUSIONS: Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy.

Suillin from the mushroom Suillus placidus as potent apoptosis inducer in human hepatoma HepG2 cells.

During the search of new anti-cancer agent from high fungi, the ethyl acetate extract of the mushroom Suillus placidus was found to exhibit a significant cytotoxic activity against human hepatoma HepG2 cells. With bioassay-guided fractionation, a cytotoxic component suillin was isolated from the extract. The anti-cancer effect of suillin was subsequently examined in 8 human cancer cell lines by using MTT assay. It is of interest to note that human liver cancer cells (HepG2 cells, Hep3B cells, and SK-Hep-1) were preferentially killed by suillin with an IC(50) of approximately 2microM in a 48h treatment. Mechanistically. suillin was found for the first time to induce apoptosis in HepG2 cells as characterized by DNA fragmentation, phosphatidyl-serine (PS) externalization, activation of caspase-3, -8, -9, depolarization of mitochondrial membrane potential, as well as release of cytochrome c into the cytosol. Moreover, the apoptosis induced by suillin was suppressed by both caspase-8 and -9 inhibitors. Western blot analysis revealed significant increases in the protein levels of Fas death receptor, adaptor FADD protein, pro-apoptotic protein Bad and a decline of Bid. These results suggest that the induction of apoptosis by suillin is through both death receptor and mitochondrial pathways. Taken together, our results suggest that suillin might be an effective agent to treat liver cancer.

[Effects of different phosphorus substrates on the growth and phosphatase activity of Skeletonema costatum and Prorocentrum donghaiense].

The effects NaH2PO4, adenosine disodium triphosphate (ATP), glucose 6-phosphate (G-6-P) and sodium beta-glycerophosphate (G-P) on the growth and phosphatase activity of Skeletonema costatum and Prorocentrum donghaiense were studied. The results showed that both species could utilize both dissolved inorganic phosphate (DIP) and dissolved organic phosphorus (DOP), and DOP had more effects on the growth of two species than DIP. For S. costatum, after 8 days, the cell abundances of the four treatments (NaH2PO4, ATP, G-6-P and G-P) were 48 x 10(4), 73 x 10(4), 63 x 10(4) and 54 x 10(4) cells/mL, respectively; For P. donghaiense, after 10 days, the cell abundances of the four treatments were 8.7 x 10(4), 15.5 x 10(4), 12.4 x 10(4) and 9.5 x 10(4) cells/mL, respectively. On the first 3-4 days, the phosphatase activity of all treatments of the two species showed a decreasing trend, but different changes were observed for the different phosphorus substrate treatments in latter days. For the NaH2PO4 treatment, both the AP and AcP activity of two species increased from the fifth day onwards. For S. costatum, the AP activity of the ATP and G-6-P treatment groups showed no obvious changes and AcP activity had a slight increase from the fifth day to the eighth day, while the activity of G-P treatment had highest phosphatase activity which increased from the fifth day on. At the end of the experiment, the AP activity of the three DOP treatment groups (ATP, G-6-P and G-P) was 0.004 x 10(-5), 0.014 x 10(-5) and 0.029 x 10(-5) U/cell, respectively, and the AcP activity was 0.006 x 10(-5), 0.011 x 10(-5) and 0.018 x 10(-5) U/cell, respectively. For P. donghaiense, both the AP and AcP activity of the three DOP treatments had similar trends, i.e., ATP < G-6-P < G-P. Under the same nutrient conditions, S. costatum had a much higher phosphatase activity and could absorb P from the environment much faster than P. donghaiense.