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Mengliang Wen - One of the best experts on this subject based on the ideXlab platform.

Tianjiao Zhu - One of the best experts on this subject based on the ideXlab platform.

  • stachybotrin g a sulfate meroterpenoid from a sponge derived fungus Stachybotrys Chartarum mxh x73
    Tetrahedron Letters, 2015
    Co-Authors: Haotian Wang, Tianjiao Zhu
    Abstract:

    Abstract Stachybotrin G (1), a new sulfate meroterpenoid possessing a unique farnesylated [1,3]diazepino[2,1-a]isoindole skeleton, was discovered from sponge derived fungus Stachybotrys Chartarum (MXH-X73). The structure was elucidated on the basis of NMR spectroscopic data and X-ray analysis.

  • phenylspirodrimanes with anti hiv activity from the sponge derived fungus Stachybotrys Chartarum mxh x73
    Journal of Natural Products, 2013
    Co-Authors: Tianjiao Zhu, Ying Guo
    Abstract:

    Seven new phenylspirodrimanes, named stachybotrins D-F (1, 3, 4), stachybocins E and F (5, 6), and stachybosides A and B (7, 8), and four known compounds (2, 9-11), were isolated from the sponge-derived fungus Stachybotrys Chartarum MXH-X73. Their structures were determined by detailed analysis of spectroscopic data. The absolute configurations of 1-8 were determined by chemical hydrolysis and modified Mosher's and Marfey's methods. All compounds were tested in an anti-HIV activity assay, and compound 1 showed an inhibitory effect on HIV-1 replication by targeting reverse transcriptase. Further study exhibited that 1 could block NNRTIs-resistant strains (HIV-1RT-K103N, HIV-1RT-L100I,K103N, HIV-1RT-K103N,V108I, HIV-1RT-K103N,G190A, and HIV-1RT-K103N,P225H) as well as wild-type HIV-1 (HIV-1wt) with EC50 values of 7.0, 23.8, 13.3, 14.2, 6.2, and 8.4 μM, respectively.

Joseph D Brain - One of the best experts on this subject based on the ideXlab platform.

  • Strain Differences Influence Murine Pulmonary Responses to Stachybotrys Chartarum
    2013
    Co-Authors: Jamie Rosenblum H. Lichtenstein, Ramon M. Molina, Thomas C. Donaghey, Joseph D Brain
    Abstract:

    When the fungus Stachybotrys Chartarum is inhaled, its mycotoxins may cause lung injury and inflammation. The severity of human responses to S. Chartarum in both occupational and home settings varies widely. To explore these differences, we intratracheally instilled C3H/HeJ, BALB/c, and C57BL/6J mice with S. Chartarum spores suspended in saline. One day later, the mice were humanely killed, bronchoalveolar lavage (BAL) was performed, and biochemical and cellular indicators of lung injury and inflammation were measured. BALB/c mice showed the highest myeloperoxidase activity, albumin and hemoglobin levels, and neutrophil numbers in their BAL among the three strains. BALB/c was the only strain to show significant increases in keratinocyte-derived cytokine (KC), monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protei

  • pulmonary responses to Stachybotrys Chartarum and its toxins mouse strain affects clearance and macrophage cytotoxicity
    Toxicological Sciences, 2010
    Co-Authors: Jamie Rosenblum H. Lichtenstein, James J. Pestka, Ramon M. Molina, Thomas C. Donaghey, Chidozie J Amuzie, Brent A Coull, Joseph D Brain
    Abstract:

    We investigated differences in the pulmonary and systemic clearance of Stachybotrys Chartarum spores in two strains of mice, BALB/c and C57BL/6J. To evaluate clearance, mice were intratracheally instilled with a suspension of radiolabeled S. Chartarum spores or with unlabeled spores. The lungs of C57BL/6J mice showed more rapid spore clearance than the lungs of BALB/c mice, which correlated with increased levels of spore-associated radioactivity in the GI tracts of C57BL/6J as compared with BALB/c mice. To identify mechanisms responsible for mouse strain differences in spore clearance and previously described lung inflammatory responses, we exposed alveolar macrophages (AMs) lavaged from BALB/c and C57BL/6J mice to S. Chartarum spores, S. Chartarum spore toxin (SST), and satratoxin G (SG) in vitro. The S. Chartarum spores were found to be highly toxic with most cells from either mouse strain being killed within 24 h when exposed to a spore:cell ratio of 1:75. The spores were more lethal to AMs from C57BL/6J than those from BALB/c mice. In mice, the SST elicited many of the same inflammatory responses as the spores in vivo, including AM recruitment, pulmonary hemorrhage, and cytokine production. Our data suggest that differences in pulmonary spore clearance may contribute to the differences in pulmonary responses to S. Chartarum between BALB/c and C57BL/6J mice. Enhanced AM survival and subsequent macrophage-mediated inflammation may also contribute to the higher susceptibility of BALB/c mice to S. Chartarum pulmonary effects. Analogous genetic differences among humans may contribute to reported variable sensitivity to S. Chartarum.

  • strain differences influence murine pulmonary responses to Stachybotrys Chartarum
    American Journal of Respiratory Cell and Molecular Biology, 2006
    Co-Authors: Jamie Rosenblum H. Lichtenstein, Ramon M. Molina, Thomas C. Donaghey, Joseph D Brain
    Abstract:

    When the fungus Stachybotrys Chartarum is inhaled, its mycotoxins may cause lung injury and inflammation. The severity of human responses to S. Chartarum in both occupational and home settings varies widely. To explore these differences, we intratracheally instilled C3H/HeJ, BALB/c, and C57BL/6J mice with S. Chartarum spores suspended in saline. One day later, the mice were humanely killed, bronchoalveolar lavage (BAL) was performed, and biochemical and cellular indicators of lung injury and inflammation were measured. BALB/c mice showed the highest myeloperoxidase activity, albumin and hemoglobin levels, and neutrophil numbers in their BAL among the three strains. BALB/c was the only strain to show significant increases in keratinocyte-derived cytokine (KC), monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-1gamma, MIP-2, RANTES, IL-1alpha, IL-1beta, IL-3, IL-6, IL-18, leukemia inhibitory factor, macrophage colony-stimulating factor, and TNF-alpha. A model of allergen-induced airway inflammation was examined to assess whether underlying allergic inflammation might contribute to increased susceptibility to S. Chartarum-induced pulmonary inflammation and injury. Surprisingly, in BALB/c mice, ovalbumin-induced airway inflammation produced a protective effect against some S. Chartarum-induced pulmonary responses. This is the first report of mammalian strain differences affecting responses to S. Chartarum. These responses differ from those reported for LPS and other fungi. Analogous underlying genetic differences may contribute to the wide range of sensitivity to Stachybotrys among humans.

  • reduction of pulmonary toxicity of Stachybotrys Chartarum spores by methanol extraction of mycotoxins
    Applied and Environmental Microbiology, 2000
    Co-Authors: Charles Albert Sakakini Nagaraja Rao, Joseph D Brain, Harriet A Burge
    Abstract:

    The fungus Stachybotrys Chartarum has been implicated in cases of nonspecific indoor air quality complaints in adults and in cases of pulmonary hemorrhaging in infants. The effects that have been described have been attributed to mycotoxins. Previous dose-effect studies focused on exposure to a single mycotoxin in a solvent, a strategy which is unlikely to accurately characterize the effects of inhaled spores. In this study we examined the role of mycotoxins in the pulmonary effects caused by S. Chartarum spores and the dose dependency of these effects. S. Chartarum spores were extracted in methanol to reduce the mycotoxin content of the spores. Then either untreated (toxin-containing) or methanol-extracted S. Chartarum spores were intratracheally instilled into male 10-week-old Charles River-Dawley rats. After 24 h, the lungs were lavaged, and the bronchoalveolar lavage fluid was analyzed to determine differences in lactic dehydrogenase, albumin, hemoglobin, myeloperoxidase, and leukocyte differential counts. Weight change was also monitored. Our data show that methanol extraction dramatically reduced the toxicity of S. Chartarum spores. No statistically significant effects were observed in the bronchoalveolar lavage fluids of the animals that were treated with methanol-extracted spores at any dose. Conversely, dose-dependent effects of the toxin-containing spores were observed when we examined the lactic dehydrogenase, albumin, and hemoglobin concentrations, the polymorphonuclear leukocyte counts, and weight loss. Our findings show that a single, intense exposure to toxin-containing S. Chartarum spores results in pulmonary inflammation and injury in a dose-dependent manner. Importantly, the effects are related to methanol-soluble toxins in the spores.

  • the time course of responses to intratracheally instilled toxic Stachybotrys Chartarum spores in rats
    Mycopathologia, 2000
    Co-Authors: Carol Y Rao, Harriet A Burge, Joseph D Brain
    Abstract:

    Stachybotrys Chartarum is a fungal species that can produce mycotoxins, specifically trichothecenes. Exposures in the indoor environment have reportedly induced neurogenic symptoms in adults and hemosiderosis in infants. However, little evidence has linked measured exposures to any fungal agent with any health outcome. We present here a study that focuses on quantitatively assessing the health risks from fungal toxin exposure. Male, 10 week old Charles River-Dawley rats were intratracheally instilled with approximately 9.6 million Stachybotrys Chartarum spores in a saline suspension. The lungs were lavaged 0 h (i.e., immediately post-instillation), 6, 24 or 72 h after instillation. Biochemical indicators (albumin, myeloperoxidase, lactic dehydrogenase, hemoglobin) and leukocyte differentials in the bronchoalveolar lavage fluid and weight change were measured. We have demonstrated that a single, acute pulmonary exposure to a large quantity of Stachybotrys Chartarum spores by intratracheal instillation causes severe injury detectable by bronchoalveolar lavage. The primary effect appears to be cytotoxicity and inflammation with hemorrhage. There is a measurable effect as early as 6 h after instillation, which may be attributable to mycotoxins in the fungal spores. The time course of responses supports early release of some toxins, with the most severe effects occurring between 6 and 24 h following exposure. By 72 h, recovery has begun, although macrophage concentrations remained elevated.

Dorr G Dearborn - One of the best experts on this subject based on the ideXlab platform.

  • RandTG,DearbornDG.Acute inflammatory responses to Stachybotrys Chartarum in the lungs of infant rats: time course and possible mechanisms. Toxicol Sci 2005;84(2): 408–17
    2015
    Co-Authors: Iwona Yike, Thomas G. R, Dorr G Dearborn
    Abstract:

    Stachybotrys Chartarum has been linked to building-related respiratory problems including pulmonary hemorrhage in infants. The macrocyclic trichothecenes produced by S. Chartarum have been the primary focus of many investigations. However, in addi-tion to trichothecenes this fungus is capable of producing other secondary metabolites and a number of protein factors. This study examines the effects of intact, autoclaved, and ethanol-extracted spores on the lungs of infant rats as an approach to differentiate between secondary metabolites and protein factors. Seven-day-old infant rats were exposed intratracheally to 1 3 105 spores/g body weight (toxic strain JS58-17) and sacrificed at various times up to 72 h. The inflammatory response was measured by morphometric analysis of the lungs and determination of inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid. Alveolar space was greatly reduced in animals exposed to funga

  • The role of fungal proteinases in pathophysiology of Stachybotrys Chartarum
    Mycopathologia, 2007
    Co-Authors: Iwona Yike, Thomas Rand, Dorr G Dearborn
    Abstract:

    The adverse health effects of Stachybotrys Chartarum have often been linked to exposure to the trichothecene mycotoxins. Recent studies have shown that in addition to mycotoxins this fungus is capable of producing and secreting in vivo proteins such as hemolysins and proteinases. Spore extracts obtained from a high trichothecene producing isolate JS 58-17 exhibited a significantly lower proteolytic activity compared to the low trichothecene producer, JS 58-06. Growing isolates on rice or potato dextrose agar results in higher proteolytic activity of the spores compared to those grown on drywall. Proteinases in the spore extracts can hydrolyze gelatin and collagen I and IV. Analysis of zymograms shows the presence of several proteins with proteolytic activity in the spores of S. Chartarum . Human tracheal epithelial cells exposed to spore extracts produced significantly higher levels of IL-6, IL-8, and TNF-α than control cells. This stimulation of cytokine production was completely abolished by Pefabloc, a serine protease inhibitor. Neutrophil numbers and proinflammatory cytokine (IL1-β and TNF-α) concentrations were highly elevated in the lungs of 7 day old rat pups exposed intratracheally to 4 × 10^4 spores/gm body weight compared to control. No significant differences in those inflammatory indices in vivo were noted between the treatments with the high trichothecene producer, isolate JS 58-17 and JS 58-06, which does not produce macrocyclic trichothecenes. Immunohistochemistry revealed reduced collagen IV labeling in spore-induced lung granulomas in rat pups exposed to both isolates. These results suggest that proteinases from S. Chartarum spores significantly contribute to lung inflammation and injury.

  • mycotoxin adducts on human serum albumin biomarkers of exposure to Stachybotrys Chartarum
    Environmental Health Perspectives, 2006
    Co-Authors: Iwona Yike, Anne M Distler, Assem G Ziady, Dorr G Dearborn
    Abstract:

    ObjectiveDespite the growing body of evidence showing adverse health effects from inhalation exposure to the trichothecene-producing mold Stachybotrys Chartarum, controversy remains. Currently, the...

  • pulmonary effects of Stachybotrys Chartarum in animal studies
    Advances in Applied Microbiology, 2004
    Co-Authors: Iwona Yike, Dorr G Dearborn
    Abstract:

    Publisher Summary Stachybotrys Chartarum is one of the several environmental fungi that can produce very potent toxic compounds. Animal models provide physicians and environmental scientists with useful tools for assessing risks associated with the respiratory effects of air pollutants. The animal studies to date support the view that pulmonary exposure to the spores of S. Chartarum leads to hemorrhagic inflammation and impairment of growth. This has been demonstrated by increases in bronchoalveolar lavage (BAL) fluid of inflammatory cells, proinflammatory mediators, hemoglobin, and proteins along with changes in pulmonary surfactant. Although the earlier experiments were conducted with relatively high doses, recent findings indicate that lower doses, which appear to be closer to the concentrations encountered in indoor air, can elicit similar symptoms. The results of animal studies based on different experimental designs are difficult to compare because of many variables—including spore toxicity, viability, and content of fungal proteins in addition to species, strains, age of animals, and route of administration.

  • localization of satratoxin g in Stachybotrys Chartarum spores and spore impacted mouse lung using immunocytochemistry
    Toxicologic Pathology, 2004
    Co-Authors: L Gregory, James J. Pestka, Dorr G Dearborn, Thomas G. Rand
    Abstract:

    Satratoxin-G (SG) is the major macrocyclic trichothecene mycotoxin produced by Stachybotrys Chartarum (atra) and has been implicated as a cause of a number of animal and human health problems including pulmonary hemorrhage in infants. However, there is little understanding where this toxin is localized in the spores and mycelial fragments of this species or in the lung impacted by SG-sequestered spores. The purpose of this study was to evaluate the distribution of SG in S. Chartarum spores and mycelium in culture, and spore-impacted mouse lung in vivo, using immunocytochemistry. SG was localized predominately in S. Chartarum spores with moderate labelling of the phialide-apex walls. Labelling was primarily along the outer plasmalemma surface and in the inner wall layer. Only modest labelling was observed in hyphae. Toxin localization at these sites supports the position that spores contain the highest satratoxin concentrations and that the toxin is constitutively produced. In impacted mouse lung, highest SG labelling was detected in lysosomes, along the inside of the nuclear membrane in nuclear heterochromatin and RER within alveolar macrophages. Alveolar type II cells also showed modest labelling of the nuclear heterochromatin and RER. There was no evidence that the toxin accumulated in the neutrophils, fibroblasts, or other cells associated with the granulomas surrounding spores or mycelial fragments. These observations indicate that SG displays a high degree of cellular specificity with respect to its uptake in mouse lung. They further indicate that the alveolar macrophages play an important role in the sequestration and immobilization of low concentrations of the toxin.

Zhanggui Ding - One of the best experts on this subject based on the ideXlab platform.