The Activation of AMPK/NRF2 Pathway in Lung Epithelial Cells Is Involved in the Protective Effects of Kinsenoside on Lipopolysaccharide-Induced Acute Lung Injury.

The disorder of mitochondrial dynamic equilibrium of lung epithelial cell is one of the critical causes of acute lung injury (ALI). Kinsenoside (Kin) serves as an active small-molecule component derived from traditional medicinal herb displaying multiple pharmacological actions in cancers, hyperglycemia, and liver disease. The objective of this study was to investigate the effects of Kin on lipopolysaccharide- (LPS-) induced ALI and further explore possible molecular mechanisms. Kin was administered orally (100 mg/kg/day) for 7 consecutive days before LPS instillation (5 mg/kg). After 12 hours, pathological injury, inflammatory response, and oxidative stress were detected. The results demonstrated that Kin significantly alleviated lung pathological injury and decreased the infiltration of inflammatory cells and the release of inflammatory mediators in bronchoalveolar lavage fluid (BALF), apart from inhibiting the production of reactive oxygen species (ROS) and lipid peroxidation. Meanwhile, Kin also promoted mitochondrial fusion and restrained mitochondrial fission in mice with ALI. In terms of mechanism, Kin pretreatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and the protein level of nuclear factor erythroid 2-related factor 2 (NRF2). In Ampk-α knockout mice challenged with LPS, Kin lost its pulmonary protective effects, accompanied by lower NRF2 level. In vitro experiments further unveiled that either AMPK inhibition by Compound C or NRF2 knockdown by siRNA abolished the protective roles of Kin in LPS-treated A549 lung epithelial cells. And NRF2 activator TAT-14 could reverse the effects of Ampk-α deficiency. In conclusion, Kin possesses the ability to prevent LPS-induced ALI by modulating mitochondrial dynamic equilibrium in lung epithelial cell in an AMPK/NRF2-dependent manner.

Novel structures of two-dimensional tungsten boride and their superconductivity.

Two-dimensional (2D) superconductors, which can be widely applied in optoelectronic and microelectronic devices, have gained renewed attention in recent years. Based on the crystal structure prediction method and first-principles calculations, we obtain four novel 2D tungsten boride structures of tetr-, hex-, and tri-W2B2 and hex-WB4 and investigate their bonding types, electronic properties, phonon dispersions and electron-phonon coupling (EPC). The results show that both tetr- and hex-W2B2 are intrinsic phonon-mediated superconductors with a superconducting transition temperature (Tc) of 7.8 and 1.5 K, respectively, while tri-W2B2 and hex-WB4 are normal metals. We demonstrate that carrier doping as well as biaxial strain can soften the low-frequency phonon modes and enhance the strength of the EPC. While the Tc of tetr-W2B2 can be increased to 15.4 K under a compressive strain of -2%, the Tc of hex-W2B2 can be enhanced to 5.9 K by a tensile strain of +4%. With the inclusion of spin-orbit couping (SOC), the value of Tc decreases by 38.5% in our systems. Furthermore, we explore the stabilities and mechanical properties of tetr- and hex-W2B2 and indicate that they may be prepared by growing on ZnS(100) and ZnS(111), respectively. Our findings provide novel 2D superconducting materials and will stimulate more efforts in this filed.

Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia-reperfusion in mice: role of Nrf2.

Intestinal ischemic post-conditioning (IPo) protects against lung injury induced by intestinal ischemia-reperfusion (IIR) partly through promotion of expression and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with HO-1 and regulates antioxidant defense. However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is not completely understood. Here we show that IPo significantly attenuated IIR-induced lung injury and suppressed oxidative stress and systemic inflammatory responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently, the beneficial effects of IPo were abolished by ATRA and Brusatol, potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays an important role in the protective effects of IPo against IIR-induced acute lung injury.

γ-Secretase inhibitor DAPT attenuates intimal hyperplasia of vein grafts by inhibition of Notch1 signaling.

The proliferation and high plasticity of vascular smooth muscle cells (vSMCs) are the major reasons for restenosis of vein grafts. N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), specific inhibitor of γ-secretase, has been shown to regulate vSMC proliferation and differentiation through the Notch signaling pathway, but the pathophysiological importance of these findings in venous grafts has not yet been determined. A rat vein graft model was employed wherein the left jugular vein was surgically interposed into the left common carotid artery. Daily subcutaneous injections of DAPT or placebo (DMSO) were administered postoperatively (control animals received no treatment). We showed that DAPT can inhibit restenosis of vein grafts by inhibiting vSMC proliferation and increasing apoptosis in vivo. Notch1 signaling was highly active during the development of intima thickening. By blocking the Notch signaling pathway, the γ-secretase inhibitor DAPT can significantly attenuated intima thickening. These changes in vein grafts coincided with enhanced binding of myocardin to the smooth muscle-specific protein SM22 and smooth muscle myosin heavy chain at the promoters of vSMC differentiation-specific genes. These studies showed that DAPT can restore the vSMC phenotype and inhibit vSMC proliferation through suppression of the Notch1 signaling pathway, and thus opens a new avenue for the treatment of restenosis in vein grafts.

[Surgical treatment of traumatic intrathoracic esophageal perforations by foreign bone].

OBJECTIVE: To evaluate the staging criteria and surgical treatment strategy of traumatic intrathoracic esophageal perforations by foreign bone. METHODS: Fifty-seven patients with intrathoracic esophageal perforations caused by foreign bone in our department from January 1980 to June 2006 were studied. Patients were divided into 4 grades: grade I was esophageal perforation without mediastinitis (n=17), grade II was esophageal perforation with severe mediastinitis (n=13), grade III was esophageal perforation with severe empyema (n=21), grade IV was esophageal perforation with tracheal or aorto-esophageal fistula (n=6). Based on the stage of esophageal perforation, operative procedures were selected including esophagotomy, esophageal repair, esophagectomy, mediastinal drainage, and esophagus reconstruction with colon. RESULTS: In grade I, II and III, all but one patient experienced satisfactory healing of the esophagus. One patient died of multi-organ failure from septic complication. No leakage was observed. Normal swallowing function and improved weight gain was achieved in all the patients. There were 2 deaths in grade IV (2/6). CONCLUSIONS: Grading of esophageal perforation caused by foreign bone is helpful to the decision of surgical treatment strategy.

[Clinicopathological analysis of esophageal carcinosarcoma:a report of 22 cases].

OBJECTIVE: To evaluate the clinicopathological characteristics and surgical treatment of esophageal carcinosarcoma. METHODS: The patients with esophageal carcinosarcoma were divided into two types according to barium swallow: intraluminal carcinosarcoma (n=20) and fungating carcinosarcoma (n=2). Only one esophageal carcinosarcoma case was diagnosed by esophagoscopic biopsy preoperatively. Twenty patients underwent left thoracic approach esophagectomy and esophagogastrostomy above aortic arch, and two patients underwent esophagectomy and esophagogastrostomy below aortic arch. RESULTS: All the cases survived during operation and had no severe complication. Post-operative biopsy revealed that 21 cases had definite boundary between the carcinoma and the sarcoma. Only one case showed the invasion of carcinomatous tissues into sarcomatous tissues and mixed growth. Four cases had lymph node metastases (18.2%). The 1-, 3- and 5-year survival rates were 90.9% (20/22), 77.3% (17/22) and 68.2% (15/22) respectively. CONCLUSIONS: Esophageal carcinosarcoma is a rare malignant tumor with little invasiveness, low lymph node metastasis, early clinical symptom occurrence, low preoperative accurate diagnostic rate and good prognosis. Surgical resection is the main treatment for esophageal carcinosarcoma.

[Observation on the long-term complications after esophageal replacement with colon].

OBJECTIVE: To study the etiology and preventive measures of the long-term postoperative complication after esophageal replacement with colon for esophageal benign disease. METHODS: To review the clinical data of 577 patients with esophageal replacement with colon our department, including 123 cases of esophageal benign disease. Of all, there were 25 cases-time for 11 cases following with severe complication: redundancy and dilated colon 12 cases-time, severe stricture of stoma 4, macrocyst esophagus 2, colon-stomach stoma expansion 4, mechanical obstruction of colon 3. The etiology included iatrogenic and functionality. The therapy included stricture form or resection, redundancy segment resection, obstructed segment solution and stoma resection and form. RESULTS: Eight cases underwent once operation, 2 case twice, 1 case three times. After operation, 9 cases took food normally, 2 improved symptoms obviously. CONCLUSIONS: The iatrogenic and functionality factor contributed to severe complication after esophageal replacement with colon for esophageal benign disease. The preventive measure is followed during operation: cervical esophageal-colon anastomosis exceed 2.5 centimeter, abdominal colon-stomach anastomosis reflux, channel width of colon passage, intestinal canal lay up straight. Re-operation is best choice to for local stricture, colon expansion, redundancy and dilated colon.

[Surgical anatomy of the colic vessels in Chinese and its influence on the operation of esophageal replacement with colon].

OBJECTIVE: To investigate the configuration of colic vessels in Chinese and its influence on the operation of esophageal replacement with colon (ERC). METHODS: The origin, trend, branching, configuration, and distribution of the colic vessels, the intensity of the colic arterial impulse, the integrity of the marginal artery at the splenic flexure and hepatic flexure of colon were observed during the operation of ERC among 582 patients undergoing ERC, 402 males mad 180 females, aged 2 approximately 74, from 22 provinces, municipality, and autonomous regions. RESULTS: The left colic artery (LCA) stemmed from the inferior mesenteric artery (IMA) in 97.3% of the patients, with an absence rate of 0.7%. The middle colic artery (MCA) stemmed from the superior mesenteric artery (SMA) in 77.8% of the patients with an absence rate of 8.2%. Accessory middle colic artery (acMCA), originating from the right colic artery, could be seen in 6.2% of the patients 39.7% of the right colic artery (RCA) stemmed from the SMA by itself, 23.0% of the RMA stemmed together with MCA, and 28.0% of the RCA stemmed together with the ileocolic artery. The absence rate of RCA was 9.8%. The intactness rate of marginal artery was 96.8% at the splenic flexure of colon, and was 88.7% at the hepatic flexure. The Rolan arch was seen in only 7.6% of the patients. CONCLUSION: The configuration of colic vessels in Chinese was basically similar to those of the results of autopsies carried out abroad. The optimal supply artery of colic segment during ERC is LCA, followed by LCA. Attention should be paid to the integrity of marginal arteries and veins in the patients with history of epigastric operation.