"Fumagillin"

The effects of protein supplementation, fumagillin treatment, and colony management on the productivity and long-term survival of honey bee (Apis mellifera) colonies. In this study, we intensively measured the longitudinal productivity and survival of 362 commercially managed honey bee colonies in Canada, over a two-year period. A full factorial experimental design was used, whereby two . In the fumagillin treatment, colonies were treated with the label dose of Fumagilin-B® each year during the fall. Neither treatment provided consistent benefits across all sites and dates. Fumagillin was associated with a large increase in honey production only at the Northern Alberta site, while protein supplementation produced an early season increase in brood production only at the Southern Alberta site

Fumagillin regulates stemness and malignancies in cancer stem-like cells derived from liver cancer via targeting to MetAP-2. Cancer relapse is associated with the presence of cancer stem-like cells (CSCs), which lead to multidirectional differentiation and unrestricted proliferative replication. Fumagillin, a myocotoxin produced by the saprophytic filamentous fungus Aspergillus fumigatus, has been reported to affect malignant characteristics in hepatocellular cancer cells. However, its exact role in CSCs is still unknown. CSCs were enriched by culturing cancer cells in serum-free medium. The effects of fumagillin on malignant cell characteristics and mitochondrial function were measured. The regulatory role of fumagillin on methionine aminopeptidase-2 (MetAP-2) was assessed. When

Fumagillin inhibits growth of the enteric protozoan parasite Entamoeba histolytica by covalently binding to and selectively inhibiting methionine aminopeptidase 2. Amebiasis is an important cause of morbidity and mortality worldwide, and caused by infection with the protozoan parasite . Metronidazole is currently the first-line drug despite adverse effects and concerns on the emergence of drug resistance. Fumagillin, a fungal metabolite from and its structurally related natural and synthetic compounds have been previously explored as potential anti-angiogenesis inhibitors for cancers, anti-microbial, and anti-obese compounds. Although fumagillin was used for human amebiasis in clinical trials in 1950s, the mode of action of fumagillin remains elusive until now. In this report, we showed

A possible role for fumagillin in cellular damage during host infection by Aspergillus fumigatus Virulence mechanisms of the pathogenic fungus Aspergillus fumigatus are multifactorial and depend on the immune state of the host, but little is known about the fungal mechanism that develops during the process of lung invasion. In this study, microarray technology was combined with a histopathology necrosis. One percent of the fungal genome followed a differential expression pattern during this process. Strikingly, most of the genes of the intertwined fumagillin/pseurotin biosynthetic gene cluster were upregulated as were genes encoding lytic enzymes such as lipases, proteases (DppIV, DppV, Asp f 1 or Asp f 5) and chitinase (chiB1) as well as three genes related with pyomelanin biosynthesis process

Physiological mechanisms of sustained fumagillin-induced weight loss Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by gut microbiota, and caloric spilling in the urine. Studies

Successful Treatment of Disseminated Anncaliia algerae Microsporidial Infection With Combination Fumagillin and Albendazole myositis is a life-threatening, emerging microsporidiosis among immunocompromised hosts. We report a case of disseminated infection in a man previously treated with alemtuzumab. Due to failure of albendazole-based therapy, fumagillin was added as a novel approach

Fumagillin Prodrug Nanotherapy Suppresses Macrophage Inflammatory Response via Endothelial Nitric Oxide Antiangiogenesis has been extensively explored for the treatment of a variety of cancers and certain inflammatory processes. Fumagillin, a mycotoxin produced by Aspergillus fumigatus that binds methionine aminopeptidase 2 (MetAP-2), is a potent antiangiogenic agent. Native fumagillin, however , is poorly soluble and extremely unstable. We have developed a lipase-labile fumagillin prodrug (Fum-PD) that eliminated the photoinstability of the compound. Using αvβ3-integrin-targeted perfluorocarbon nanocarriers to deliver Fum-PD specifically to angiogenic vessels, we effectively suppressed clinical disease in an experimental model of rheumatoid arthritis (RA). The exact mechanism by which Fum-PD

Production, characterization and therapeutic efficacy of egg yolk antibodies specific to Nosema ceranae. Nosema disease, caused by Nosema ceranae, one of the single-celled fungal microsporidian parasites, is one of the most important and common diseases of adult honey bees. Since fumagillin, which has been used for decades in the control of Nosema disease in honey bees (Apis mellifera), poses

. bieneusi. There may be a response to oral fumagillin (20 mg tds for 14 days) but with significant haematological toxicity [114,115]. Encephalitozoon spp. including E. intestinalis are susceptible to albendazole (400 mg bd for 21 days) and this drug is recommended for initial therapy in addition to cART. Longer therapy may be required for involvement of sites outside the GI tract or in severe disease

. Fumagillin, an antimicrosporidiosis drug, is a therapeutic agent with potential for the treatment of giardiasis. However, it exhibits considerable, albeit reversible, toxicity when used to treat immunocompromised microsporidiosis patients. Fumagillin is also a highly unstable compound. To address these liabilities, we designed and synthesized stable fumagillol derivatives with lower levels of permeation across polarized epithelial Caco-2 cells and better potency against trophozoites than fumagillin. Metronidazole-resistant strains were also susceptible to the new fumagillol derivatives. In addition, these compounds were more potent against the amebiasis-causing parasite than fumagillin. Two compounds exhibited better thermal and acid stability than fumagillin, which should prolong the drug shelf

TNP-470 skews DC differentiation to Th1-stimulatory phenotypes and can serve as a novel adjuvant in a cancer vaccine Fumagillin is an antiangiogenic and antineoplastic fungal natural product, and TNP-470 is one of its most potent analogs. Decades of studies revealed that TNP-470 has potent anticancer activities via destruction of neovasculature. In stark contrast, TNP-470 has been reported

approach. The additional structural information provided by regulatory modules allows for topological analyses. As a result, we detected a significant association of omics data with distinct biological processes such as regulation of kinase activity, transport mechanisms or amino acid metabolism. We also found a previously unreported increased production of the secondary metabolite fumagillin

associated with fumagillin and pseurotin biosynthesis highlighted the anti-virulence activity of NCT. These results indicate that NCT induces an oxidative stress response in A. fumigatus as evidenced by alterations in the proteome and inhibits conidial and mycelial growth. Clinical investigations of topical application of NCT to treat Aspergillus infections are encouraged.

Enterocytozoon bieneusi Microsporidiosis in Stem Cell Transplant Recipients Treated with Fumagillin1. Enterocytozoon bieneusi microsporidiosis is an emerging disease in immunocompromised patients. We report 2 cases of this disease in allogeneic hematopoietic stem cell transplant patients successfully treated with fumagillin. Thrombocytopenia occurred but without major adverse events . Modifications of immunosuppression could be avoided when E. bieneusi is rapidly identified and fumagillin therapy is started promptly.

. Proteins associated with fungal filamentation, such as septin and kinesin, were detected only 4 h after germination (hag). A transcription factor related to biosynthesis of the secondary metabolite fumagillin, which can form hybrids with polyketides, was induced 2 hag, and polyketide synthase was observed 4 hag. The accumulation of ATP synthase, binding immunoglobulin protein (BiP), and catalase

A. fumigatus (GA-L7) which were identified as: pseurotin A, pseurotin D, pseurotin F2, fumagillin, tryprostatin C, gliotoxin and bis(methylthio)gliotoxin. Addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile with an enhanced production of a metabolite, fumiquinazoline C by tenfolds. In order to assess the effect of valproic acid on the biosynthetic pathway

nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Anti-neovascular effectiveness of αβ-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0.01) in the upper airways/bronchi

prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths' survival