2H-Pyranone and isocoumarin derivatives isolated from the plant pathogenic fungus Leptosphaena maculans.

Two new 2H-pyranones and two new isocoumarin derivatives, maculanslines A-D (1-4), together with seven known compounds (5-11), were isolated from the plant pathogenic fungus Leptosphaena maculans. Their planar structures and absolute configuration were elucidated by comprehensive spectroscopic techniques including high-resolution electrospray ionization mass spectrum, 1D and 2D nuclear magnetic resonance, as well as electronic circular dichroism. All 11 compounds were tested for their inhibitory activity against α-glucosidase. Compound 1 showed moderate inhibitory activity against α-glucosidase with IC50 of 74.35 µM.

Mitochondrial dynamics regulates hypoxia-induced migration and antineoplastic activity of cisplatin in breast cancer cells.

Mitochondria are high dynamic organelles with frequent fission and fusion. Here, we found hypoxia stimulated Drp1 expression, mitochondrial fission and migration in metastatic MDA-MB­231 cells, but not in non-metastatic MCF-7 cells. Inhibition of Drp1-dependent mitochondrial fission by Mdivi-1 or silencing Drp1 attenuated hypoxia-induced mitochondrial fission and migration in MDA-MB­231 cells. On the other hand, cisplatin induced significant apoptosis and mitochondrial fission in MDA-MB­231 cells, but not in MCF-7 cells. Mdivi-1 and silencing Drp1 also efficiently prevented cisplatin-induced MMP decrease, ROS production and apoptosis in MDA-MB­231 cells. Our data suggest that Drp1-dependent mitochondrial fission not only regulates hypoxia-induced migration of breast cancer cells, but also facilitates its sensitivity to chemotherapeutic agents. Thus, targeting Drp1-dependent mitochondrial dynamics may provide a novel strategy to suppress breast cancer metastasis and improve the chemotherapeutic effect in the future.

Dramatic decrease of aortic longitudinal elastic strength in a rat model of aortic dissection.

BACKGROUND: This study aimed to evaluate thoracic aortic longitudinal elastic strength in a rat model of aortic dissection (AD). METHODS: Young Sprague Dawley rats were fed 0.25% ß-aminopropionitrile (BAPN). Biomechanical and biochemistry properties of the aorta were analyzed. Elasticity modulus, maximum stretching length, draw ratio, maximum load, maximum strength, and maximum extensibility were measured. RESULTS: More than one-half of BAPN-treated rats (52.9%) died of aortic rupture secondary to AD during the experiment. The diameter of the aneurysms was 6.33 ± 1.17 mm and the length was 9.33 ± 4.95 mm. The maximum diameter was significantly increased in BAPN-treated rats with AD (group B2) compared with rats without AD (group B1) and control group (group A) (P = 0.001 and P < 0.001, respectively), but was not different between group B1 and group A (P = 0.108). Thickness of media and initial area in aorta of BAPN-treated rats were significantly increased compared with control group (P = 0.001 and P < 0.001, respectively), but no difference in initial area was observed between group B1 and group B2 (P = 0.54). Maximum stretching length, draw ratio, maximum load, maximum strength, maximum extensibility, and elasticity modulus were dramatically decreased in group B2 compared with group B1 and group A (group B2 vs. group B1: P < 0.001; group B1 vs. group A: P < 0.001). CONCLUSIONS: We successfully established a rat model of AD with a high incidence of rupture and mortality. Examinations of strain and stress parameters as well as elasticity modulus of the dissected and the nondissected aorta help understand pathogenesis of AD.

Overexpression of interleukin-1ß and interferon-γ in type I thoracic aortic dissections and ascending thoracic aortic aneurysms: possible correlation with matrix metalloproteinase-9 expression and apoptosis of aortic media cells.

OBJECTIVE: To examine the expression of interleukin-1ß and interferon-γ and their possible roles in aortic dissections and aneurysms. METHODS: Aortic specimens were obtained from patients with type I thoracic aortic dissection, ascending thoracic aortic aneurysms, and control organ donors. The expression of interleukin-1ß, interferon-γ, matrix metalloproteinase-9, and signal transduction factors phospho-p38 and phosphorylated c-jun N-terminal kinase (phospho-JNK) were detected by real time reverse transcription-polymerase chain reaction (real time RT-PCR), Western blot, and immunohistochemistry, respectively. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed to detect apoptosis of media cells. The correlation of these factors and apoptosis was also studied. RESULTS: Apoptosis in the media of thoracic aortic dissection and in ascending thoracic aortic aneurysms was dramatically higher than in the control group. The expression of interleukin-1ß gradually increased from the control group, thoracic aortic dissection to ascending thoracic aortic aneurysms (p < 0.01, respectively). The expression of interferon-γ and matrix metalloproteinase-9 was significantly increased in the media of thoracic aortic dissection and ascending thoracic aortic aneurysms compared with the control group (p < 0.01, respectively). There were positive correlations between interleukin-1ß versus matrix metalloproteinase-9, interleukin-1ß versus phospho-p38 in thoracic aortic dissection (p < 0.01, respectively), and interferon-γ versus matrix metalloproteinase-9, interferon-γ versus phospho-JNK, interferon-γ versus apoptosis, and interleukin-1ß versus apoptosis in ascending thoracic aortic aneurysms (p = 0.02, 0.02, p < 0.01, p < 0.01). CONCLUSIONS: Interleukin-1ß and interferon-γ might effect the formation of thoracic aortic dissection and ascending thoracic aortic aneurysms possibly through the up-regulation of matrix metalloproteinase-9 and the apoptosis of media cells in humans.

A study of the expression and interaction of Destrin, cofilin, and LIMK in Debakey I type thoracic aortic dissection tissue.

OBJECTIVE: Our previous proteomic research has indicated that some cytoskeleton proteins show differential expression between thoracic aortic dissection and normal control groups, which suggests a possible mechanism involved in the pathogenesis of the vascular remodeling of this disease. This study was to investigate the expression of these cytoskeleton proteins and their possible molecular pathway in the remodeling process of thoracic aortic dissection. METHODS: Ascending aortic segments were obtained from thoracic aortic dissection patients (Debakey type I, n = 13) and age-matched normal donors (n = 8). Quantitative differences of Destrin, cofilin, and LIM protein kinases (LIMK) were investigated using RT-PCR and Western blot analysis. The relationships between the expression of these proteins and clinical parameters such as age, hypertension and maximal aortic diameter of the patients were analysed statistically. RESULTS: Western blotting showed that the protein expression of cofilin and LIMK was significantly decreased in thoracic aortic dissection tissue compared with normal control, (p = 0.004 for cofilin, p < 0.001 for LIMK). The mRNA levels of cofilin and LIMK were lower in thoracic aortic dissection than normal control and were coincident with the protein expression (p = 0.0039 for cofilin, p = 0.017 for LIMK). A significant correlation (Spearman's rho = -0.521, p = 0.019) was found between LIMK protein expression and maximal aortic diameter; lower levels of LIMK expression were associated with larger aortic diameters. CONCLUSIONS: Changes in the expression of cytoskeletal regulatory proteins such as LIMK and cofilin may play a role in weakening thoracic aortic medial tissue, as a precondition to thoracic aortic dissection.

[Endovascular exclusion of juxtarenal abdominal aortic aneurysm with one-piece customized fenestrated endovascular stent-graft].

OBJECTIVE: To evaluate the technical feasibility of juxtarenal abdominal aortic aneurysm (AAA) repair with fenestrated endovascular stent-graft METHODS: A 64-year-old male was diagnosed with juxtarenal AAA with severe coronary artery stenosis, fenestrations was customized according to precise helical CT data to accommodate visceral and renal arteries. Under general anesthesia and dynamic supervision of digital subtraction angiography (DSA), juxtarenal AAA was excluded with the customized fenestrated stent-graft and balloon expandable mini stent-grafts were deployed into bilateral renal arteries respectively. RESULTS: After operation, DSA showed the patency of the super mesenteric artery, bilateral renal arteries and left hypogastric artery, no endoleak was found. The serum creatinine decreased slightly after operation. CT angiography revealed favorable morphology of the stent-graft without tortuosity, migration, disjoint and endoleak 10 days after the operation and patency of super mesenteric artery, bilateral renal arteries and left hypogastric artery. CONCLUSIONS: The placement of customized fenestrated endovascular stent-graft is a feasible option for juxtarenal AAA.

Role of nitric oxide and inducible nitric oxide synthase in human abdominal aortic aneurysms: a preliminary study.

BACKGROUND: Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase (iNOS), and their possible role in AAA. METHODS: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel chi2 test and Kendall' Tau correlation. RESULTS: Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P < 0.05) and the patients with occlusive arteries (P < 0.05). iNOS protein and media NOx (nitrite + nitrate) also increased in cultured SMCs from human AAA (n = 4, P < 0.05), while plasma NOx decreased in patients with AAA (n = 25) compared to the healthy controls (n = 20). There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall (Kendall coefficient = 0.5032, P = 0.0029). CONCLUSIONS: SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.