Cryptococcus neoformans (C. neoformans) and Candida albicans (C. albicans) are classified as the critical priority groups among the pathogenic fungi, highlighting the urgent need for developing more effective antifungal therapies. On the basis of antifungal natural product sampangine, herein, a series of tricyclic oxime and oxime ether derivatives were designed. Among them, compound WZ-2 showed excellent inhibitory activity against C. neoformans (MIC₈₀ = 0.016 μg/mL) and synergized with fluconazole to treat resistant C. albicans (FICI = 0.078). Interestingly, compound WZ-2 effectively inhibited virulence factors (e.g., capsule, biofilm, and yeast-to-hypha morphological transition), suggesting the potential to overcome drug resistance. In a mouse model of cryptococcal meningitis, compound WZ-2 (5 mg/kg) effectively reduced the brain C. neoformans H99 burden. Furthermore, compound WZ-2 alone and its combination with fluconazole also significantly reduced the kidney burden of the drug-resistant strain (0304103) and sensitive strain (SC5314) of C. albicans.

01 Nov 2020·Journal of Hazardous MaterialsQ1 · ENVIRONMENTAL SCIENCE & ECOLOGY

Bacterial compatibility and immobilization with biochar improved tebuconazole degradation, soil microbiome composition and functioning

Q1 · ENVIRONMENTAL SCIENCE & ECOLOGY

Article

Author: Saleem, Muhammad ; Yang, Yong ; Zhang, Haonan ; Zhang, Qingming ; Miao, Jingbo ; Sun, Tong

Tebuconazole is a widely used fungicide that may impair soil health. Presently, limited information is available on the bioremediation of tebuconazole-contaminated soil using biochar as a carrier for bacteria. In this study, we firstly isolated a tebuconazole-degrading strain and identified it as Alcaligenes faecalis WZ-2. Then, we used wheat straw-derived biochar as carrier to capture strain WZ-2 to assemble microorganism-immobilized composite. Finally, we investigated the effects of strain WZ-2 and biochar-immobilized WZ-2 on tebuconazole biodegradation, microbial enzyme activities and community composition in the contaminated soil. Results showed that, as compared to control, the strain WZ-2 and biochar-immobilized WZ-2 accelerated the degradation of tebuconazole, while reducing the half-life of tebuconazole from 40.8 to 18.7 and 13.3 days in soil, respectively. However, biochar alone than control slightly retarded the degradation of tebuconazole in soil. Though tebuconazole (10 mg/kg) negatively affected the soil enzyme activities (urease, dehydrogenase, and invertase) and microbiome community structure, the biochar-immobilized WZ-2 not only accelerated the degradation of tebuconazole but also restored native soil microbial enzyme activities and microbiome community composition. Our results suggest that a compatible combination of bacteria with biochar is an attractive and efficient approach for remediation of pesticide-contaminated soil and improvement of soil biological health.

01 Mar 2001·Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao

[Effects of estradiol and isoflavoid on the expression of adhesion molecules on neutrophils].

Article

Author: Tian, W ; Lei, S ; Chen, Y ; Chen, H ; Peng, R

OBJECTIVETo elucidate the effects of estradiol and isoflavoid on the expression of adhesion molecules on neutrophils.METHODSNeutrophils of healthy subjects and ischemic stroke patients were treated with tumor necrosis factor alpha (TNF alpha), in the presence or absence of different concentrations of isoflavoid (WZ1, WZ2) and estradiol (WZ3, WZ4). Flow cytometry was used to detect the expression of CD18 and CD62L on neutrophil surface.RESULTS1. 10 ng/ml TNF alpha could activate neutrophils of healthy subjects; it increased the expression of CD18 by 10% on neutrophil surface and shed CD62L from the surface as shown by a 15% decrease of the fluorescence intensity and a 30% decrease of the percentage of positive cell. 2. Isoflavoid (WZ1, WZ2) had no significant effect on the expression of CD18 and CD62L on neutrophils. 3. Pretreatment of neutrophils with estradiol (WZ3, WZ4) could inhibit the activation of neutrophils by TNF alpha, which decreased the fluorescence intensity of CD18 by 8%, increased the fluorescence intensity of CD62L by 15% and increased the percentage of CD62L positive cell by 20%. 4. TNF alpha could activate the neutrophils of ischemic stroke patients strikingly; it increased the fluorescence intensity of CD18 by 20% and decreased the fluorescence intensity and percentage of positive cell of CD62L by 30%, and there was a significant difference when the patients were compared with the healthy subjects. Estradiol had the same effect on the expression of CD18 and CD62L as on those of healthy subjects.CONCLUSION1. TNF alpha is a strong activator of neutrophils; it plays an important role in the occurrence and development of ischemic stroke. 2. Isoflavoid has no obvious effect on the expression of adhesion molecules on neutrophils, so its role in protecting the cardiovascular system may come into play not by the way of affecting adhesion molecules expression. 3. Pretreatment of neutrophils with estradiol could protect them from activation by TNF alpha, thus decreasing the expression of adhesion molecules, the adhesion of neutrophils -endothelial cells, and hence the risk of ischemic stroke. However, in case that the neutrophils have been activated by TNF alpha, estradiol has no effect on the expression of adhesion molecules; this implies that estradiol possibly has no valid anti-adhesion therapeutic effect on ischemic stroke.

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Indication	Highest Phase	Country/Location	Organization	Date
Meningitis, Cryptococcal	Preclinical	China	The Second Military Medical University	15 Mar 2024

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