Hai Yuan

Protective effect of HMGB1 a box on organ injury of acute pancreatitis in mice.

Objectives: To investigate the effects of high-mobility group box 1 (HMGB1) A box in experimental severe acute pancreatitis (SAP). Methods: Severe acute pancreatitis was induced by 20% l-arginine abdominal cavity injection in Institute of Cancer Research mice, and the treatment group received 2 abdominal cavity injections of A box 12 and 24 hours after the modeling injection. The serum levels of HMGB1, amylase, lipase, and biochemical indicators were measured 24 and 48 hours after induction of SAP. The pathological changes of the pancreas, lung, kidney, and liver for both SAP group and treatment group were observed and compared, as well as survival rate and surviving time. Results: A box significantly improved the elevation of the serum levels of HMGB1, amylase, lipase, and biochemical indicators in SAP. The pathological changes of pancreas and organ injury in treatment group were more alleviated than that in SAP group. The mice survival rate of the treatment group (66.7%) was significantly higher than that of the SAP group (26.7%). Conclusions: A box has remarkable protective effect against pancreatitis and associated organ injury; HMGB1 probably participates in the inflammatory reaction and organ injury of SAP as a late-acting mediator of inflammation.

TLR4-mediated NF-κB signaling pathway mediates HMGB1-induced pancreatic injury in mice with severe acute pancreatitis.

Severe acute pancreatitis (SAP) is an extremely dangerous acute abdominal disorder which causes multiple complications and has a high mortality rate. Previous research has suggested that high-mobility group box 1 (HMGB1) plays an important role in the pathogenesis of SAP; however, the mechanisms underlying this strong correlation remain unclear. In this study, to further investigate whether HMGB1 acts as a stimulating factor, and whether Toll-like receptor 4 (TLR4) acts as its major mediator in the development of pancreatic injury during SAP, recombinant human HMGB1 (rhHMGB1) and TLR4-deficient mice were used. We found that HMGB1 and TLR4 were highly expressed, and nuclear factor-κB (NF-κB) was activated in our mouse model of SAP. We noted that the rhHMGB1 pancreas-targeted injection activated the TLR4-mediated NF-κB signaling pathway and induced pancreatic injury in wild-type mice. In TLR4-deficient mice, the rhHMGB1-induced activation of NF-κB and pathological changes in the pancreas were less evident than in wild-type mice. Therefore, this study provides evidence that HMGB1 promotes the pathogenesis of pancreatitis, and its downstream TLR4-mediated NF-κB signaling pathway is a potential important mediator in the development of this form of pancreatic injury.

High-mobility-group box protein 1 A box reduces development of sodium laurate-induced thromboangiitis obliterans in rats

OBJECTIVE High-mobility-group box protein 1 (HMGB1), as a late mediator of inflammation, plays a key role in inflammatory responses by inducing and extending the production of proinflammatory cytokines. The effect of HGMB1 in the inflammatory disease thromboangiitis obliterans (TAO) is unknown. We aimed to investigate the role of HMGB1 in sodium laurate-induced TAO in rats. METHODS Male Wistar rats were randomly divided into five groups (n=8 each) for treatment: normal, sham-operated, TAO model, and low-dose (15 mg/kg) or high-dose (30 mg/kg) recombinant A box (rA box) infection (administered intraperitoneally once daily for 15 days). The TAO model was induced by sodium laurate and graded by gross appearance on day 15 after femoral artery injection. Histologic changes were measured by histopathology in rat femoral arteries. Plasma levels of HMGB1, thromboxane B2, 6-keto-prostaglandin F1-α, and blood cell counts and blood coagulation levels were measured. Expression of HMGB1, receptor for advanced glycation end-products (RAGE), interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was assessed by immunohistochemistry and immunofluorescence, Western blot analysis, and quantitative reverse-transcription polymerase chain reaction. RESULTS The typical signs and symptoms of TAO were observed on day 15 after sodium laurate injection. The expression of HMGB1, RAGE, interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was markedly increased in rat femoral arteries. Plasma levels of HMGB1 and thromboxane B2 were elevated, but the level of 6-keto-prostaglandin F1-α was decreased. Blood was in a hypercoagulable state, and prothrombin, thrombin, and activated partial thromboplastin times were all significantly shortened, whereas fibrinogen level was increased in TAO rats compared with sham-operated rats. These effects were terminated by the HMGB1 antagonist rA box. CONCLUSIONS HMGB1 is involved in the inflammatory state in a model of TAO induced by sodium laurate in rats, probably via its receptor RAGE. As the antagonist of HMGB1, rA box can attenuate the development of TAO, which may be a potential therapeutic target for the treatment of TAO.

The effect of HMGB1 A box on lung injury in mice with acute pancreatitis.

The objective of this study is to observe the effect of high-mobility group protein B1 A Box (HMGB1 A) box on lung injury in mice with acute pancreatitis and its effect on the level of high-mobility group protein B1 (HMGB1) in lung, to explore the mechanism. A total of 60 male Institute of Cancer Research mice were randomly divided into control group (n = 30) and treatment group (n = 30). Severe acute pancreatitis mice model was induced by 20% L-Arg intraperitoneal injection. The recombination HMGB1 A box was used in treatment after modeling. All the mice were killed under anesthesia at 24 and 48 h after the modeling injection. The level of HMGB1 and activity of myeloperoxidase (MPO) in lung were measured. The pathological changes of lung were observed. The level of HMGB1 in lung of A box treatment group decreased more significantly 24 h and 48 h after modeling compared with control group. The activity of MPO in lung of A box treatment group decreased more significantly 24 h after modeling compared with control group. The lung tissue pathologic score of A box treatment group decreased more significantly 48 h after modeling compared with control group. HMGB1 expression levels in the lungs were positively related to histological score of injured lung in acute pancreatitis. It indicates that HMGB1 A box is remarkably protective to lung injury induced by acute pancreatitis.

Leiomyoma of the Femoral Vein: A Case Report and Review of the Literature

Leiomyomas are benign smooth muscle tumors. A leiomyoma originating from the vein is rare. We describe a primary femoral vein tumor that was diagnosed as an unusual leiomyoma in a 50-year-old woman. It was the first reported leiomyoma in the femoral vein in English studies. We have reviewed the studies on leiomyoma from the blood vessel and summarized their characteristics, therapies, and prognosis.

Technical issues and clinical outcomes of endovascular repair of isolated iliac artery aneurysms: A single-center experience

Purpose Isolated iliac artery aneurysms are the relatively uncommon condition. This study aims to evaluate the technical issues and clinical outcomes of endovascular repair in a cohort of isolated iliac artery aneurysms treated. Methods We retrospectively reviewed 22 consecutive patients with isolated iliac artery aneurysms between December 2006 and September 2016. Iliac artery aneurysms were treated in one of the three ways: (1) standard bifurcated aortic stent graft placement with limb extension; (2) coverage of iliac artery aneurysms with covered stent grafts; and (3) embolization of the arterial branches distal to the aneurysms with coils or vascular plugs. Results Twenty-two patients (20 men) with a mean age 64.7 years underwent endovascular repair during the study period. The median diameter of the isolated iliac artery aneurysms was 5.9 ± 1.7 cm (2.9–9.0 cm). Technical success was 95.5%. Conversion to open surgery was performed in one patient with bilateral internal iliac artery aneurysms. Four patients underwent placement of a bifurcated stent graft. A covered stent graft was deployed in 16 patients, with embolization of internal iliac artery in 14 patients. Simple coil embolization of isolated internal iliac artery aneurysm was performed in one patient. There was one sudden cardiac death on day 4 after the procedure due to heart failure. During the follow-up period (range: 1–50 months, mean 19.8 months), five patients died of causes not related to isolated iliac artery aneurysms, and transient buttock claudication was observed in one patient. Conclusions Our study documents the safety and effectiveness of endovascular repair of isolated iliac artery aneurysms with low morbidity and mortality.

Alleviation of A disintegrin and metalloprotease 10 (ADAM10) on thromboangiitis obliterans involves the HMGB1/RAGE/ NF-κB pathway

Thromboangiitis obliterans (TAO), also known as Buergers disease, is a nonatherosclerotic inflammatory disease that influences medium- and small-sized blood vessels of extremities. However, mechanisms underlying TAO are still unclear. As a mediator associated with inflammation, A disintegrin and metalloprotease 10 (ADAM10) was hypothesized to play inhibitory roles in the development of TAO. Thus, the objective of this study is to investigate the effects of ADAM10 in a sodium laurate-induced TAO rat model and elucidate underlying mechanisms. Male Wistar rats were randomly divided into four groups (n = 6) for treatment: sham-operated (SHAM), TAO model (TAO), ADAM10 low dose injection (3 mg/kg; ADAM10-LD) and ADAM10 high dose injection (6 mg/kg; ADAM10-HD). After 14-day treatment, color Doppler ultrasound and hematology analysis indicated TAO rats displayed higher whole blood viscosity and blood platelet count compared with those in the SHAM group. Histologic evaluation and transmission electron microscopy revealed that the ultrastructural damages of vascular smooth muscle and endothelial cells were observed in TAO rats, such as fractured endoplasmic reticulum, decreased cell counts, and fibrillation. On the other hand, the typical signs and symptoms of TAO rats were significantly alleviated via ADAM10 treatment with a dose-dependent pattern. Real-time PCR and western blot results revealed that the expression of high-mobility-group box 1 (HMGB1), receptor for advanced glycation end-products (RAGE) and nuclear factor-kappa B (NF-κB) increased in TAO rats whereas decreased by ADAM10 treatment in both mRNA and protein levels. In conclusion, the results suggest ADAM10 alleviates symptoms of sodium laurate-induced TAO in rats via the RAGE/NF-κB signaling pathway and provides insight into the molecular basis and a potential therapeutic strategy for TAO.

Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

Background and aims Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods AAA was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. Results Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. Conclusions Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA.

PC220 Angiotensin 1-7 Suppresses Experimental Abdominal Aortic Aneurysms

within tobacco smoke have not been differentiated. The objective of this study was to compare the cellular effects of tobacco smoke vs nicotine on human aortic smooth muscle cells (HASMCs) and to look at the histologic changes in the aorta of wild-type (WT) and hyperlipidemic (apolipoprotein E knockout) mice exposed to solubilized tobacco smoke. Methods: We treated HASMCs with differing dilutions of solubilized tobacco smoke (2 cigarettes solubilized per 1 mL of buffer) to look at the relationship between solubilized tobacco smoke or nicotine concentration and cell death. Osmotic pumps with solubilized tobacco smoke were implanted into both WT and hyperlipidemic mice to investigate the effects of solubilized tobacco smoke exposure on the mouse aorta. Histologic and cellular changes in the abdominal