Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective To investigate the causes,diagnosis and treatment of small intestine bleeding.Methods Sixty-eight cases of small intestine bleeding from January 2000 to June 2010 were retrospectively analyzed.Among all cases,4 underwent routine hemostatic treatment under colonoscopy,40treated with open surgery and 24 patients with laparoscopic therapy.Among them,57 cases underwent part resection for some small intestine,completely laparoscopic resection of diverticula was performed in 7patients.Results Neoplasms was the leading cause of small intestine bleeding,accounting for 48.5％ (33/68)in these patients,followed by small intestine diverticulum accounted for 29.4％ ( 20/68 ),intestinal infective diseases accounted for 14.7％ ( 10/68 ) and vascular disease accounted for 7.4％ ( 5/68 ).Conclusion The clinical manifestations of small intestinal bleeding showed no specific signs.Neoplasm,intestine diverticulum and intestinal infective diseases are the most common causes of small intestinal bleeding.Small intestinal bleeding can be diagnosed in intraoperative colonoscopy.Surgery is the most effective treatment for small intestinal bleeding.