Glycolysis Inhibition Alleviates Cardiac Fibrosis After Myocardial Infarction by Suppressing Cardiac Fibroblast Activation.

Objective: To explore the role of glycolysis in cardiac fibroblast (CF) activation and cardiac fibrosis after myocardial infarction (MI). Method: In vivo: 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was injected into the abdominal cavity of the MI or sham mice every day. On the 28th day, cardiac function was measured by ultrasonic cardiography, and the hearts were harvested. Masson staining and immunofluorescence (IF) were used to evaluate the fibrosis area, and western blot was used to identify the glycolytic level. In vitro, we isolated the CF from the sham, MI and MI with 2-DG treatment mice, and we also activated normal CF with transforming growth factor-ß1 (TGF-ß1) and block glycolysis with 2-DG. We then detected the glycolytic proteins, fibrotic proteins, and the concentrations of lactate and glucose in the culture medium. At last, we further detected the fibrotic and glycolytic markers in human fibrotic and non-fibrotic heart tissues with masson staining, IF and western blot. Result: More collagen and glycolytic protein expressions were observed in the MI mice hearts. The mortality increased when mice were treated with 2-DG (100 mg/kg/d) after the MI surgery (Log-rank test, P < 0.05). When the dosage of 2-DG declined to 50 mg/kg/d, and the treatment was started on the 4th day after MI, no statistical difference of mortality between the two groups was observed (Log-rank test, P = 0.98). The collagen volume fraction was smaller and the fluorescence signal of α-smooth muscle actin (α-SMA) was weaker in mice treated with 2-DG than PBS. In vitro, 2-DG could significantly inhibit the increased expression of both the glycolytic and fibrotic proteins in the activated CF. Conclusion: Cardiac fibrosis is along with the enhancement of CF activation and glycolysis. Glycolysis inhibition can alleviate cardiac fibroblast activation and cardiac fibrosis after myocardial infarction.

Mitochondrial Fission and Mitophagy Reciprocally Orchestrate Cardiac Fibroblasts Activation.

Although mitochondrial fission has been reported to increase proliferative capacity and collagen production, it can also contribute to mitochondrial impairment, which is detrimental to cell survival. The aim of the present study was to investigate the role of mitochondrial fission in cardiac fibroblasts (CF) activation and explore the mechanisms involved in the maintenance of mitochondrial health under this condition. For this, changes in the levels of mitochondrial fission/fusion-related proteins were assessed in transforming growth factor beta 1 (TGF-ß1)-activated CF, whereas the role of mitochondrial fission during this process was also elucidated, as were the underlying mechanisms. The interaction between mitochondrial fission and mitophagy, the main defense mechanism against mitochondrial impairment, was also explored. The results showed that the mitochondria in TGF-ß1-treated CF were noticeably more fragmented than those of controls. The expression of several mitochondrial fission-related proteins was markedly upregulated, and the levels of fusion-related proteins were also altered, but to a lesser extent. Inhibiting mitochondrial fission resulted in a marked attenuation of TGF-ß1-induced CF activation. The TGF-ß1-induced increase in glycolysis was greatly suppressed in the presence of a mitochondrial inhibitor, whereas a glycolysis-specific antagonist exerted little additional antifibrotic effects. TGF-ß1 treatment increased cellular levels of reactive oxygen species (ROS) and triggered mitophagy, but this effect was reversed following the application of ROS scavengers. For the signals mediating mitophagy, the expression of Pink1, but not Bnip3l/Nix or Fundc1, exhibited the most significant changes, which could be counteracted by treatment with a mitochondrial fission inhibitor. Pink1 knockdown suppressed CF activation and mitochondrial fission, which was accompanied by increased CF apoptosis. In conclusion, mitochondrial fission resulted in increased glycolysis and played a crucial role in CF activation. Moreover, mitochondrial fission promoted reactive oxygen species (ROS) production, leading to mitophagy and the consequent degradation of the impaired mitochondria, thus promoting CF survival and maintaining their activation.

Influenza B virus-associated pneumonia in pediatric patients: clinical features, laboratory data, and chest X-ray findings.

BACKGROUND: The clinical significance of influenza B is frequently overlooked, and reports on influenza B pneumonia in children are limited. Therefore, the clinical features of associated complications have rarely been reported. The aim of this study is to evaluate the clinical characteristics in pediatric patients with influenza B virus-associated pneumonia. METHODS: From January 2009 to February 2012, 389 consecutive patients under 18 years old with influenza B virus infection were enrolled into the study. Thirty-four patients were defined as the pneumonia group by clinical symptoms and chest X-ray (CXR) findings, and 90 patients who had laboratory data and normal CXR findings were recruited to form the nonpneumonia group. RESULTS: The age of the patients in the pneumonia group was significantly younger (median of 5.3 vs. 6.6 years). The white blood cell count (median of 7.5 vs. 5.7 × 10(9) cells/L) and C-reactive protein level (median of 21.1 vs. 5.7 mg/L) were higher, but the hemoglobin level was lower (median of 12.6 vs. 13.2 g/dL) in the pneumonia group. The CXR findings revealed that 29.4% of patients had alveolar consolidation, 32.4% had interstitial infiltration, and 38.2% had ground glass opacity. Two of four patients with pleural effusion had a positive bacteria culture, and both of them died. CONCLUSION: Pneumonia should be considered in pediatric patients with influenza B virus infection presenting with younger age, higher white blood cell count, lower hemoglobin, and higher C-reactive protein level. The CXR findings were varied. Patients with pleural effusion and positive bacterial culture may have more severity of clinical outcome.

Controlling surface plasmon of several pair arrays of silver-shell nanocylinders.

We studied, numerically, the characteristics of the surface plasmon of a system consisting of several pair arrays of silver-shell nanocylinders. Effects from different numbers of pair arrays, illumination wavelengths, and the core refractive index of silver-shell nanocylinders are studied by using the finite-element method. Results show that the peak wavelengths shift to shorter wavelengths (blueshifted) when the number of pair arrays increases from three to six. The near-field intensities in the gaps of the proposed type 1 structure can be tuned much stronger with a redshift by varying the wavelength of the incident light. The main features of surface plasmon effects can be qualitatively understood from some simple models of three, four, five, and six pairs of silver-shell nanocylinders.