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Photodiagnosis and Photodynamic Therapy · 2019 · IF 2.589

In vitro photodynamic inactivation effects of hypocrellin B on azole-sensitive and resistant Candida albicans

Asif Jan,Chengcheng Liu,Hong Deng,Jiao Li,Wenpeng Ma,Xiaoyan Zeng,Yanhong Ji

Background and aim The extensive use of antifungal drugs has led to resistance from Candida albicans . The search for alternative treatment against drug-resistant C. albicans is highly desirable. Antimicrobial photodynamic therapy (aPDT) is an emerging and promising approach for treating localized and superficial C. albicans infections. The aim of this study was to investigate the photodynamic inactivation (PDI) effects of hypocrellin B (HB) on azole-sensitive and resistant C. albicans in vitro . Methods The PDI efficacies of HB on standard C. albicans strain (ATCC 10231), azole-sensitive clinical isolate of C. albicans , and azole-resistant clinical isolate of C. albicans were assessed. The uptake of HB in C. albicans cells was investigated by confocal laser scanning microscopy (CLSM). The PDI effects on cellular structure and surface characteristics were investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Results HB exhibited no significant dark toxicity, but inactivated the azole-sensitive and resistant C. albicans in a light-dose and PS concentration-dependent manner. CLSM images indicated that PDI treated C. albicans cells showed stronger fluorescence compared to untreated cells. TEM images suggested that significant damage to the cell wall, membrane, and cytoplasm were induced by HB-mediated PDI. SEM analysis revealed that the surface of C. albicans cells became twisted and ruptured after PDI treatment. Conclusions Azole-sensitive and resistant C. albicans could be effectively inactivated by HB in the presence of light, and HB-mediated aPDT shows promise as an antifungal treatment for C. albicans .

CAS / MDL: 23491-52-3
研究领域: 微生物学 · 药理学 · 医学研究
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MOLECULES · 2019 ·Vol. 24 ·期 7 ·1394 · IF 3.06

Correlation between Chemical Composition and Antifungal Activity of Clausena lansium Essential Oil against Candida spp.

Xiaowen He,Lantong Zhang,Jinping Chen,Jinlei Sui,Guohui Yi,Jinyan Wu,Yinzheng Ma

Essential oils (EOs) have been shown to have a diversity of beneficial human health effects.Clausenais a large and highly diverse genus of plants with medicinal and cosmetic significance. The aim of this study was to analyze the composition ofClausena lansiumEOs and to investigate their potential antifungal effects. The chemical compositions ofClausena lansiumEOs obtained by hydrodistillation were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 101 compounds were identified among the diverse extracts ofC. lansium. EOs of leaves and pericarps from different cultivars (Hainan local wampee and chicken heart wampee) collected in Hainan (China) were classified into four clusters based on their compositions. These clusters showed different antifungal activities against fiveCandidaspecies (C. albicans,C. tropicalis,C. glabrata,C. kruseiandC. parapsilosis) using the disc diffusion method.Clausena lansiumEOs of pericarps displayed noteworthy antifungal activitives against all the testedCandidastrains with inhibition zone diameters in the range of 11.1–23.1 mm. EOs of leaves showed relatively low antifungal activities with inhibition zone diameters in the range of 6.5–22.2 mm. The rank order of antifungal activities among the four EO clusters was as follows: Cluster IV> Cluster III > Cluster I ≥ Cluster II. These results represent the first report about the correlation between chemical composition ofC. lansiumEOs and antifungal activity. Higher contents of β-phellandrene, β-sesquiphellandrene and β-bisabolene in EOs of pericarps were likely responsible for the high antifungal activity of Cluster IV EOs. Taken together, our results demonstrate the chemical diversity ofClausena lansiumEOs and their potential as novel antifungal agents for candidiasis caused byCandidaspp. Furthermore, the obtained results showing a wide spectrum of antifungal activities provide scientific evidence for the traditional use of these plants.Keywords:correlation;Clausena lansium;essential oil;antifungal activity;Candidaspp.

研究领域: 植物学 · 药理学
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INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY · 2017 · IF 3.505

Nerol triggers mitochondrial dysfunction and disruption via elevation of Ca2+ and ROS in Candida albicans

Jun Tian,Zhaoqun Lu,Yanzhen Wang,Man Zhang,Xueyan Wang,Xudong Tang,Xue Peng,Hong Zeng

The antifungal activity of Nerol (NEL) against Candida albicans , a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4   mM that causes noteworthy candidacidal activity through an apoptosis-like mechanism. Calcium (Ca 2+ ) levels and reactive oxygen species (ROS) production, which are the major causes of apoptosis, were determined in C. albicans cells treated with NEL and were found to increase, which related to mitochondrial dysfunction and disruption. A series of characteristic changes of apoptosis caused by NEL, including mitochondrial membrane depolarization, cytochrome c (cyt c) release, and metacaspase activation were examined using a flow cytometer and Western blot . The results showed that an increase in intracellular Ca 2+ and ROS led to dramatically decreased mitochondrial membrane potential (MMP); cyt c was also released from the mitochondria to the cytosol. Other early apoptotic features were also observed with the metacaspase activation. Finally, the morphological changes of the cells were observed, including phosphatidylserine (PS) externalization, nuclear condensation, and DNA fragmentation through Annexin V-FITC and PI double staining, TUNEL assay , and DAPI staining. The results supported the hypothesis that NEL was involved in the apoptosis of C. albicans cells not only at the early stages, but also at the late stages. In summary, NEL can trigger mitochondrial dysfunction and disruption via elevation of Ca 2+ and ROS leading to apoptosis in C. albicans . This research on the mechanism of cell death triggered by NEL against C. albicans has important significance for providing a novel treatment of C. albicans infections.

研究领域: 微生物学 · 药理学 · 细胞生物学
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PHYTOMEDICINE · 2018 · IF 3.61

Caffeic acid phenethyl ester synergistically enhances the antifungal activity of fluconazole against resistant Candida albicans

Lingmei Sun,Kai Liao,Chengcheng Hang

Background Owing to the increased morbidity and mortality associated with invasive fungal infections , treatments with a combination of antifungal agents are often considered. Caffeic acid phenethyl ester (CAPE), a major active component of propolis, possesses many biological activities , including antibacterial, antiviral, antioxidant, anti-inflammatory, and anticancer effects. Purpose This study aimed to evaluate the interaction between CAPE and fluconazole (FLC) against Candida albicans . Methods Microdilution checkerboard and time-kill assays were employed to evaluate the in vitro interaction between CAPE and FLC. The data obtained from the checkerboard tests were analyzed by the fractional inhibitory concentration index (FICI).The antifungal activity of the CAPE and FLC combination was evaluated in vivo in a Caenorhabditis elegans model of infection. Results We observed that when used in combination, CAPE acted synergistically with FLC against FLC-resistant clinical isolates of C. albicans . In addition, the CAPE-FLC combination significantly extended the longevity and reduced fungal burden in C. elegans when compared with treatment with FLC or CAPE alone. Conclusion These results indicate that the use of CAPE and FLC in combination has considerable therapeutic potential against resistant C. albicans .

CAS / MDL: 104594-70-9
研究领域: 医学 · 微生物学 · 药理学
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RESEARCH IN MICROBIOLOGY · 2022 · IF 3.946

2-Alkyl-anthraquinones inhibit Candida albicans biofilm via inhibiting the formation of matrix and hyphae

Yuanyuan Song,Ziqi Wang,Yijing Long,Yang Mao,Feng Jiang,Yuanyuan Lu

Candida albicans can form biofilm on biotic and abiotic surfaces of medical implants to cause superficial and systemic infections under specific condition. The formation of hyphae and matrix of C. albicans are considered as probable virulence factors . We assessed the inhibitory activities of 26 anthraquinones against C. albicans biofilm formation, which were substituted by different functional groups including hydroxyl groups, amino groups, carboxyl groups, alkyl groups, and glycoside groups at C1- or C2-position. Among them, anthraquinones without substituents at other positions but only an alkyl group attached to C2-position, namely 2-alkyl-anthraquinones were determined to have significant anti-biofilm activities. Furthermore, 2-ethylanthraquinone can significantly affect genes related to extracellular matrix ( PMT6 and IFD6 ), and hyphal formation ( HWP1 , ECE1 and EFG1 ), leading to the disrupted formation of biofilm, by detail transcriptomics analysis. We believed that 2-ethylanthraquinone could inspire more discoveries of anti-biofilm agents against C. albicans .

研究领域: 微生物学 · 药理学 · 分子生物学
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BIOCHEMICAL PHARMACOLOGY · 2023 · IF 5.8

Fatty acid modification of antimicrobial peptide CGA-N9 and the combats against Candida albicans infection

Ruifang Li,Xuxia Wang,Kedong Yin,Qingpeng Xu,Shiming Ren,Xueqin Wang,Zichao Wang,Yanjie Yi

High-efficiency and low-toxic antimicrobial peptides (AMPs) are supposed to be the future candidates to solve the increasingly prominent problems of Candida albicans infection and drug resistance. Generally, introduction of hydrophobic moieties on AMPs resulted in analogues with remarkably increased activity against pathogens. CGA-N9, an antifungal peptide found in our lab, is a Candida -selective antimicrobial peptide capable of preferentially killing Candida spp. relative to benign microorganisms with low toxicities. We speculate that fatty acid modification could improve the anti- Candida activity of CGA-N9. In the present investigation, a set of CGA-N9 analogues with fatty acid conjugations at N-terminus were obtained. The biological activities of CGA-N9 analogues were determined. The results showed that the n-octanoic acid conjugation of CGA-N9 (CGA-N9-C8) was the optimal CGA-N9 analogue with the highest anti- Candida activity and biosafety; exhibited the strongest biofilm inhibition activity and biofilm eradication ability; and the highest stability against protease hydrolysis in serum. Furthermore, CGA-N9-C8 is less prone to develop resistance for C. albicans in reference with fluconazole ; CGA-N9-C8 also exhibited Candidacidal activity to the planktonic cells and the persister cells of C. albicans ; reduced C. albicans susceptibility in a systemic candidiasis mouse model. In conclusion, fatty acid modification is an effective method to enhance the antimicrobial activity of CGA-N9, and CGA-N9-C8 is a promising candidate to defend C. albicans infection and resolve C. albicans drug resistance.

研究领域: 微生物学 · 药学 · 传染病学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2023 · IF 4.4

Rapid prediction method of ZIF-8 immobilized Candida rugosa lipase activity by near-infrared spectroscopy

Shiyi Chen,Mengli Ma,Juan Peng,Xiaogang He,Qian Wang,Ganghui Chu

Candida rugosa lipase (CRL, EC3.1.1.3) is one of the main enzymes synthesizing esters, and ZIF-8 was chosen as an immobilization carrier for lipase. Enzyme activity testing often requires expensive reagents as substrates, and the experiment processes are time-consuming and inconvenient. As a result, a novel approach based on near-infrared spectroscopy (NIRs) was developed for predicting CRL/ZIF-8 enzyme activity. The absorbance of the immobilized enzyme catalytic system was evaluated using UV–Vis spectroscopy to investigate the amount of CRL/ZIF-8 enzyme activity. The powdered samples' near-infrared spectra were obtained. The sample’s enzyme activity data were linked with each sample’s original NIR spectra to establish the NIR model. A partial least squares (PLS) model of immobilized enzyme activity was developed by coupling spectral preprocessing with a variable screening technique. The experiments were completed within 48 h to eliminate inaccuracies between the reduction in enzyme activity with increasing laying-aside time throughout the test and the NIRs modeling. The root-mean-square error of cross-validation (RMSECV), the correlation coefficient of validation set (R) value, and the ratio of prediction to deviation (RPD) value were employed as assessment model indicators. The near-infrared spectrum model was developed by merging the best 2nd derivative spectral preprocessing with the Competitive Adaptive Reweighted Sampling (CARS) variable screening method. This model's root-mean-square error of cross-validation (RMSECV) was 0.368 U/g, the correlation coefficient of calibration set (R_cv) value was 0.943, the root-mean-square error of prediction (RMSEP) set was 0.414 U/g, the correlation coefficient of validation set (R) value was 0.952, and the ratio of prediction to deviation (RPD) was 3.0. The model demonstrates that the fitting relationship between the predicted and the reference enzyme activity value of the NIRs is satisfactory. The findings revealed a strong relationship between NIRs and CRL/ZIF-8 enzyme activity. As a result, the established model could be implemented to quantify the enzyme activity of CRL/ZIF-8 quickly by including more variations of natural samples. The prediction method is simple, rapid, and adaptable to be the theoretical and practical basis for further studying other interdisciplinary research work in enzymology and spectroscopy.

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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY · 2014 ·Vol. 172 ·期 6 ·3128-3140 · IF 1.687

Effects of Additives on Lipase Immobilization in Microemulsion-Based Organogels

Zhang Wei-Wei,Wang Na,Zhang Ling,Wu Wan-Xia,Hu Cheng-Li,Yu Xiao-Qi

An inexpensive, facile, and environmentally benign method was developed to improve the activity and stability of Candida rugosa lipase (triacylglycerol acylhydrolase) immobilized on microemulsion-based organogels (CRL MBGs) via the addition of additives during immobilization. The additives used were polyethylene glycol (PEG) or polysaccharides. This study is the first report on the effect of additives in CRL MBGs. Among the tested additives, PEG produced the most improvement in the immobilized CRL, enhancing its stability in organic solvents (specifically polar solvents). The results of circular dichroism and fluorescence spectra experiments indicated that exposure of the acidic CRL to electronegative additives in the buffer, such as polyethylenimine and the electropositive surfactant cetyltrimethylammonium bromide, may change the lipase secondary structure, ultimately causing enzyme inactivation. However, sodium bis(2-ethylhexyl)sulfosuccinate and PEG 2000 had minimal effects on the secondary structure of CRL. The CRL MBGs containing PEG 2000 demonstrated remarkable retention of their catalytic activity during the recycling test. No significant changes in enzymatic activity were observed, even after nine runs, and 90 % of the original yield was maintained after 15 cycles.

CAS / MDL: 7585-39-9 60-12-8
研究领域: 生物技术 · 酶学 · 化学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2021 · IF 5.268

Maleimide-functionalized phospholipid/Pluronic F127 mixed micelles for efficient ophthalmic delivery of voriconazole against Candida albicans

Baohuan Wu,Sixiang Sai,Keke Li,Xingchen Sun,Jingtian Han,Baocheng Tian

Drugs that are topically applied on the eyes have low bioavailability, which has always been an important problem. In this study, maleimide functionalized, voriconazole (VCZ) loaded mixed micelles (Mal-VCZ-MM) were designed. Pluronic F127 and phospholipid were used as materials, and maleimide was used as an adhesive. The prepared Mal-VCZ-MM was nearly spherical with a particle size of 84.45 ± 1.39 nm and a zeta potential of − 20.3 ± 0.29 mV. The encapsulation efficiency of Mal-VCZ-MM was 95.33 ± 0.06%, and it had high stability with a critical micelle concentration value of 1.28 × 10 -4 mg/mL. CCK-8 assay showed that its cytotoxicity was lower than that of free VCZ solution (VCZ-Sol). Both quantitative and qualitative analyses of the HCE-T cellular uptake showed that the cellular internalization of Mal-C6-MM was significantly stronger than that of C6-MM. The endocytosis pathway was macropinocytosis-mediated, cavernous-mediated, and energy-dependent. In vitro results against Candida albicans showed that the diameters of the antifungal inhibition zones of VCZ-Sol, VCZ-MM, and Mal-VCZ-MM were 15.5 ± 0.50 mm, 24.0 ± 0.71 mm, and 31.5 ± 1.12 mm, respectively. The antifungal effect of Mal-VCZ-MM was significantly higher than that of VCZ-Sol and VCZ-MM ( P  < 0.001). This study shows that Mal-VCZ-MM is a highly effective hydrophobic ophthalmic drug-delivery carrier that can improve the therapeutic effect of the drug.

研究领域: 药剂学 · 药物递送 · 眼科学 · 微生物学
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-5 · IF 4.259

Engineering a lipase B from Candida antactica with efficient perhydrolysis performance by eliminating its hydrolase activity

Wang Xu-Ping,Zhou Peng-Fei,Li Zhi-Gang,Yang Bo,Hollmann Frank,Wang Yong-Hua

A Ser105Ala mutant of the lipase B from Candida antarctica enables ‘perhydrolase-only’ reactions. At the example of the chemoenzymatic Baeyer-Villiger oxidation of cyclohexanone, we demonstrate that with this mutant selective oxidation can be achieved in deep eutectic solvent while essentially eliminating the undesired hydrolysis reaction of the product.

研究领域: 生物化学 · 酶工程 · 绿色化学
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FIBERS AND POLYMERS · 2018 ·Vol. 19 ·期 8 ·1611-1617 · IF 1.353

Expanding Application of Immobilized Candida Antarctica Lipase B: A Green Enzyme Catalyst for Knoevenagel Condensation Reaction

Wang Cuie,Wang Ning,Liu Xinhua,Wan Peng,He Xinwei,Shang Yongjia

We propose a green synthesis of benzopyran compound based on immobilized lipase. Firstly, by using a combined electrospun membrane and biocompatible chitosan, we show that the chitosan-functionalized electrospun PMA-co-PAA fibrous membrane can provide effective anchoring sites for immobilization of the Candida antarctica lipase B (CALB), and a maximum loading amount of CALB (152 mg/g) can be achieved. Then, the resulting membrane displays enhanced stability in catalyzing Knoevenagel condensation reaction of salicylaldehyde with active methylene compound in mixed aqueousorganic media. The catalytic activity and stability of the CALB on chitosan-modified fiber is better than its non-immobilized counterpart. Furthermore, this immobilize CALB catalyst still retained about 45 % of the initial activity after 5 cycles, which potentially had implications for the design of “green” enzyme catalyst for sustainable organic synthesis.

研究领域: 生物化学 · 绿色化学 · 材料科学
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Virulence · 2026 · IF 6.8

Repurposing the antispasmodic drug pinaverium bromide as a novel antifungal agent and synergist against Candida albicans

Jing Yao,Zhiyu Yang,Xudong Hang,Tianyu Chen,Binglei Li,Ting Shi,Keao Quan,Jingchen Xu,Liping Zeng,Ganzhu Feng,Hongkai Bi

Fungal infections represent a significant and growing threat to public health, exacerbated by an expanding population of immunocompromised individuals and the increasing prevalence of resistance to conventional antifungal agents. Drug repurposing offers a strategic and efficient pathway for antifungal discovery, leveraging existing pharmacotherapies to reduce development costs and mitigate safety risks. This study evaluated the antifungal potential of pinaverium bromide, an FDA-approved antispasmodic drug for functional gastrointestinal disorders, against the prevalent pathogen Candida albicans. Our in vitro analyses revealed that pinaverium bromide demonstrated standalone antifungal activity and acted synergistically with amphotericin B or azole drugs. Moreover, it effectively attenuated key virulence factors of C. albicans, including hyphal formation and biofilm development. The therapeutic efficacy of both monotherapy and combination therapy with amphotericin B or voriconazole was validated in two murine models of systemic candidiasis. Mechanistically, pinaverium bromide disrupted mitochondrial function, induced apoptotic cell death, and impaired iron homeostasis in C. albicans. When combined with amphotericin B, it potentiated the drug’s effect by amplifying reactive oxygen species accumulation and enhancing membrane permeabilization. These findings support the potential of pinaverium bromide as a novel antifungal agent, either when used alone or in combination with established antifungal therapies.

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