Bioactive Materials
·
2025
·
IF 20.3
Lei Zhang,Kailai Liu,Jiachen Zhou,Yuchen Zhang,Jinpeng Wen,Jiangchuan He,Yunhe Zheng,Li Yang,Ke Wang,Jun Tian
Cutaneous fungal infections, particularly those caused by Candida albicans , pose significant clinical challenges due to high recurrence rates and rising antifungal resistance. Conventional therapies, including azoles and polyenes, are limited by toxicity, resistance, and cost. This study addresses these limitations by developing a multifunctional hydrogel integrating lauric acid (LA)-a natural antifungal anionic surfactant-with the antioxidant plant polyphenol myricetin (Myr). The synergistic combination of LA and Myr disrupts fungal membrane integrity through lipid bilayer destabilization. To enhance therapeutic delivery, myricetin laurate ester was encapsulated in DSPE-PEG2000 micelles and embedded into a hydrogel matrix formed by crosslinking oxidized chondroitin sulfate and hydrazide-functionalized PEG. The resulting hydrogel demonstrated potent antifungal activity against C. albicans by disrupting cell membranes and alleviating oxidative stress in infected wounds. In vitro assays confirmed minimal cytotoxicity to mammalian cells, while in vivo studies in ICR mice showed accelerated healing of C. albicans -infected skin lesions. The hydrogel's sustained release profile and biocompatibility highlight its potential as a dual-action therapeutic platform, combining antifungal efficacy with antioxidant wound repair. This innovative strategy offers a promising solution to overcome drug resistance, reduce toxicity, and improve outcomes in managing cutaneous candidiasis and related dermatomycoses.
研究领域:
皮肤病学
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微生物学
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药剂学
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生物材料
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再生医学
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产品关联
DOI
PubMed
高影响因子
Acupuncture and Herbal Medicine
·
2024
·Vol. 4
·期 1
·113
·
IF 0
Huang Dandan,Tang Zhongjie,Pu Xiao,Wang Tianqi,Gao Feiyan,Li Chong
Objective: In this study, we aim to enhance the anti-prostate cancer efficacy of cabazitaxel (CTX) and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1 (Rk1/CTX-Lip). Methods: Physical and chemical properties of Rk1/CTX-Lip were investigated. We evaluated the biological functions of Rk1/CTX-Lip, both in vitro and in vivo . A subcutaneous prostate cancer (RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors. Simultaneously, a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip. Finally, biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated. Results: We successfully prepared Rk1/CTX-Lip, achieving high CTX encapsulation efficiency (97.24 ± 0.75)% and physical stability. Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis, effective tumor tissue targeting, and a significant reduction (>50%) in average tumor volume compared with Chol/CTX-Lip. Moreover, it relieved the concurrent infection burden and effectively regulated immune organs and cells, demonstrating superior biocompatibility. Conclusion: Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity. Export
研究领域:
药剂学
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肿瘤学
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免疫学
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微生物学
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DOI
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Dinghao Hou,Yu Rao,Xiaonan Yuan,Qingxiang He,Yuxuan Wang,Jiangna Guo,Feng Yan
Owing to the high invasion depth and easy formation of biofilms, the treatment of subcutaneous fungal infection is intractable and challenging. Herein, we report an injectable and biodegradable hydrogel with bactericidal, quorum sensing inhibition and antioxidant activities for the in situ treatment of subcutaneous fungal infection. The hydrogel (BEPE) was constructed by irradiating mixed bovine serum albumin (BSA), ε-polylysine and epigallocatechin gallate (EGCG)-loaded mesoporous polydopamine (PDA) under near-infrared (NIR) light. BEPE exerted microbicidal effects against Candida albicans (99.5%) and Streptococcus mutans (99.6%) through synergistic photothermal effects and the microbiocidal activity of slowly released ε-polylysine. Moreover, the gently released EGCG from BEPE with relatively high bioavailability, synergistically inhibited and destroyed biofilms by inhibiting quorum sensing between microbes, resulting in an antibiofilm efficiency of 80.5% against C. albicans. An in vivo subcutaneous fungal infection study revealed that BEPE accelerates tissue regeneration via targeted formation, elimination of fungal infection and alleviation of inflammation in situ, thereby promoting wound healing. This biodegradable hydrogel strategy will facilitate the design of multifunctional microbicidal agents for targeted subcutaneous fungal infection treatment.
研究领域:
生物材料学
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微生物学
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感染性疾病治疗
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DOI
PubMed
高影响因子
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
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2023
·
IF 4.7
Xinying Sui,Xinyu Cheng,Zhaodi Li,Yonghong Wang,Zhenpeng Zhang,Ruyue Yan,Lei Chang,Yanchang Li,Ping Xu,Changzhu Duan
Fungal infections and antifungal resistance are the increasing global public health concerns. Mechanisms of fungal resistance include alterations in drug-target interactions, detoxification by high expression of drug efflux transporters, and permeability barriers associated with biofilms. However, the systematic panorama and dynamic changes of the relevant biological processes of fungal drug resistance acquisition remain limited. In this study, we developed a yeast model of resistance to prolonged fluconazole treatment and utilized the isobaric labels TMT (tandem mass tag)-based quantitative proteomics to analyze the proteome composition and changes in native, short-time fluconazole stimulated and drug-resistant strains. The proteome exhibited significant dynamic range at the beginning of treatment but returned to normal condition upon acquisition drug resistance. The sterol pathway responded strongly under a short time of fluconazole treatment, with increased transcript levels of most enzymes facilitating greater protein expression . With the drug resistance acquisition, the sterol pathway returned to normal state, while the expression of efflux pump proteins increased obviously on the transcription level. Finally, multiple efflux pump proteins showed high expression in drug-resistant strain. Thus, families of sterol pathway and efflux pump proteins, which are closely associated with drug resistance mechanisms, may play different roles at different nodes in the process of drug resistance acquisition. Our findings uncover the relatively important role of efflux pump proteins in the acquisition of fluconazole resistance and highlight its potential as the vital antifungal targets.
研究领域:
微生物学
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药物研发
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
Vaccines
·
2023
·Vol. 11
·期 10
·1521
·
IF 7.8
Zirun Zhao,Ying Sun,Mingchun Li,Qilin Yu
The development of efficient fungal vaccines is urgent for preventing life-threatening systemic fungal infections. In this study, we prepared a synthetic, cell-based fungal vaccine for preventing systemic fungal infections using synthetic biology techniques. The synthetic cell EmEAP1 was constructed by transforming theEscherichia colichassis using a de novo synthetic fragment encoding the protein mChEap1 that was composed of theE. coliOmpA peptide, the fluorescence protein mCherry, theCandida albicansadhesin Eap1, and the C-terminally transmembrane region. The EmEAP1 cells highly exposed the mChEap1 on the cell surface under IPTG induction. The fungal vaccine was then prepared by mixing the EmEAP1 cells with aluminum hydroxide gel and CpG. Fluorescence quantification revealed that the fungal vaccine was stable even after 112 days of storage. After immunization in mice, the vaccine resided in the lymph nodes, inducing the recruitment of CD11c+dendritic cells. Moreover, the vaccine strongly activated the CD4+T splenocytes and elicited high levels of anti-Eap1 IgG. By the prime-boost immunization, the vaccine prolonged the survival time of the mice infected by theC. albicanscells and attenuated fungal colonization together with inflammation in the kidneys. This study sheds light on the development of synthetic biology-based fungal vaccines for the prevention of life-threatening fungal infections.Keywords:fungal vaccine;systemic fungal infection;Candida albicans;adhesin;synthetic biology;protection
研究领域:
微生物学
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免疫学
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合成生物学
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疫苗学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Xun Tianrong,Rong Yan,Lv Bin,Tian Jinfei,Zhang Qing,Yang Xixiao
Purpose: Voriconazole (VOR) is combined with atorvastatin (ATO) to treat fungal infections in patients with dyslipidemia in clinical practice. However, the pharmacokinetic interactions and potential mechanisms between them are unknown. Therefore, this study aimed to investigate the pharmacokinetic interactions and potential mechanisms between ATO and VOR.Patients and methods: We collected plasma samples from three patients using ATO and VOR. Rats were administered either VOR or normal saline for 6 days, followed by a single dose of 2 mg/kg ATO, and then plasma samples were collected at different time points. The incubation models of human liver microsomes or HepG2 cells were constructed in vitro. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system was developed to determine the concentration of ATO, 2-hydroxy-ATO, 4-hydroxy-ATO, and VOR.Results: In patients, VOR significantly reduced the metabolism of ATO and slowed the formation of 2-hydroxy- and 4-hydroxy-ATO. In rats pretreated with orally administered VOR for 6 days or normal saline given a single dose of 2 mg/kg ATO administered orally on Day 6, the t1/2 of ATO was significantly prolonged from 3.61 to 6.43 h, and the area under the concentration-time curve (AUC0–24h) values of ATO increased from 53.86 to 176.84 h μg.L−1. However, the pharmacokinetic parameters of VOR (20 mg/kg) with or without pretreatment with ATO (2 mg/kg) only slightly changed. In vitro studies indicated that VOR inhibited the metabolism of ATO and testosterone, and the IC50 values were 45.94 and 49.81 μM. However, no significant change in transporter behaviors of ATO was observed when VOR or transporter inhibitors were co-administered.Conclusion: Our study demonstrated that VOR has significant interactions with ATO, probably due to VOR’s inhibition of the CYP3A4-mediated metabolism of ATO. Based on the clinical cases and potential interactions, the basic data obtained in our study are expected to help adjust the dose of ATO and promote the design of rational dosage regimens for pharmacotherapy for fungal infections in patients with dyslipidemia.
研究领域:
药理学
·
临床药理学
·
药物代谢
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产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2025
·
IF 4.5
Xingwang Wang,Yue Wang,Hongbin Zhang,Yang Zhao,Jie Zeng,Rui Gao,Ziheng Chen,Kai Lv,Dong Ma,Jianyong Fan
Superficial fungal infections, refering to infections of the skin and soft tissues caused by fungi invading superficial areas of the human body such as the skin and nails, predominantly by dermatophytes like Trichophyton and yeasts. Traditional antifungal treatments face limitations such as resistance, irritation, and compliance issues. Nitric oxide (NO) has gained attention for its broad-spectrum antimicrobial properties, but its volatility and uncontrolled release hinder medical use. Thus, loading NO into suitable carriers for sustained release has become a solution. In this study, a thermosensitive hydrogel wound dressing NO@CS@β-GP (NO@CP) is prepared. Chitosan (CS) and β-glycerophosphate (β-GP) with excellent biocompatibility, degradability, and tunability are used as the hydrogel framework to provide an ideal platform for NO loading and release, which is promising for the treatment of fungal skin infections.
研究领域:
医学
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药学
·
生物材料学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jing Liu,Hao Chen,Yan Lv,Lijun Yang,Wenjie Wang,Jianying Huang,Dandan Zhang
The mycotoxin-producing fungi contamination of foodstuffs and agricultural commodities is a serious problem. In this study, the efficacy of acetic acid (AcA), chitosan (CS), and CS with extra AcA (CS/extra AcA) against Aspergillus flavus ( A. flavus ) in vitro and in vivo were investigated. Results showed that CS/extra AcA strongly inhibited the mycelial growth and aflatoxins production of A. flavus at lower concentrations than CS (MIC > 16.0 mg/mL) or AcA (MIC: 0.31 %). Significant inhibition was achieved in the presence of 4.0/0.12 and 8.0/0.08 CS (mg/mL)/extra AcA (%). CS/extra AcA exhibited remarkable antifungal activities based on the results of spore germination inhibition, abnormalities of spore morphology, disruption of cell membrane, mitochondrial dysfunction, and induction of apoptosis of hyphae. Moreover, pathogenicity test in peanut kernels showed that 8.0/0.16 CS (mg/mL)/extra AcA (%) could effectively inhibit the fungal infection and aflatoxin B 1 production. The efficacy of CS/extra AcA is possibly due to the synergy of the antifungal property of CS, and undissociated AcA. The findings referred that CS/extra AcA is safe, efficient, and economical, and it could be used as a promising way to control A. flavus contamination in agro-foods preservation.
研究领域:
食品科学
·
微生物学
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DOI
PubMed
高影响因子
Cellular & Molecular Immunology
·
2022
·Vol. 19
·期 5
·602-618
·
IF 22.096
Ma Xiaojian,Tan Xi,Yu Bingbing,Sun Wanwei,Wang Heping,Hu Huijun,Du Yanyun,He Ruirui,Gao Ru,Peng Qianwen,Cui Zhihui,Pan Ting,Feng Xiong,Wang Junhan,Xu Chengqi,Zhu Bin,Liu Wei,Wang Chenhui
Fungal infections cause ~1.5 million deaths each year worldwide, and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria. The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species. Therefore, a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies. Here, we report that DOCK2 (dedicator of cytokinesis 2) promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages. DOCK2-deficient macrophages exhibit decreased RAC GTPase (Rac family small GTPase) activation and ROS (reactive oxygen species) production, which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways. Mechanistically, after fungal stimulation, activated SYK (spleen-associated tyrosine kinase) phosphorylates DOCK2 at tyrosine 985 and 1405, which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation. Importantly, nanoparticle-mediated delivery of in vitro transcribed (IVT) Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo. Taken together, this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.
研究领域:
免疫学
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微生物学
·
分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 6
·667
·
IF 6
Wanqian Li,Yanru Feng,Zhe Feng,Li Wang,Malcolm Whiteway,Hui Lu,Yuanying Jiang
Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, the fungistatic nature of FLC renders pathogenic fungi capable of developing tolerance towards it. Consequently, converting FLC into a fungicidal agent using adjuvants assumes significance to circumvent FLC resistance and the perpetuation of fungal infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as a promising adjuvant for enhancing the fungicidal activity of FLC from a comprehensive library of 2372 FDA-approved drugs. PIT could render FLC fungicidal even at concentrations as low as 1 μM. The median lethal dose (LD50) of PIT was determined to be 103.6 mg/kg. We have discovered that PIT achieves its synergistic effect by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, and disrupting Golgi function. We employed aCandida albicansstrain that demonstrated a notable tolerance to FLC to infect mice and found that PIT effectively augmented the antifungal efficacy of FLC against IFIs. This study is an illustrative example of how FDA-approved drugs can effectively eliminate fungal tolerance to FLC.
研究领域:
药理学
·
微生物学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Gao-Feng Qi,Xin Cui,Xue-Feng Gong,Xu Cui,Huan-Ge Xu,Qi-Lin Liang,Kuo Zhang,Xiao-Ling Sha,Litao Li,Gui-Yuan Wang,Hong-Wen Liang,Lei Wang
Fungal infections contribute substantially to human morbidity and mortality. Particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows the morphological transformation of biphasic fungi, inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broadspectrum antifungal fluconazole, AFP achieved the comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibits the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy than fluconazole. In systemic candidiasis mice model, AFP showed similar efficacy with first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for the anti-fungal infection.
研究领域:
药学
·
微生物学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Zhenzhen Weng,Qi Wei,Cheng Ye,Yingying Xu,Jie Gao,Wei Zhang,Lubing Liu,Yue Zhang,Jiangnan Hu,Qin Zhong,Jian Sun,Xiaolei Wang
Fungal infection possesses the characteristics of high invasion depth and easy formation of a biofilm under the skin, which greatly hinders the treatment process. Here, traditional Chinese medicine moxa is carbonized and modified with zinc oxide (ZnO) nanosheets to synthesize carbonized moxa@ZnO (CMZ) with the dual response properties of yellow light (YL) and ultrasound (US) for synergistic antifungal therapy. CMZ with narrow bandgap can respond to long-wavelength YL that is highly safe and helpful for skin repair. Simultaneously, CMZ with a piezoelectric effect can further enhance the photocatalytic efficiency under the stimulation of US with high tissue penetration. Gene mechanism investigation indicates that when exposed to US and YL irradiation, CMZ-based therapy can adjust the expression of genes associated with fungal virulence, metabolic activity, mycelial growth and biofilm development, thus efficaciously eradicating planktonic Candida albicans (C. albicans) and mature biofilm. Importantly, despite the 1.00 cm thick tissue barrier, CMZ can rapidly eliminate 99.9% of C. albicans within 4 min, showing a satisfactory deep fungicidal efficacy. The in vivo therapeutic effect of this strategy is demonstrated in both open wound and deep cutaneous infection tests, speaking of dramatically better efficacy than the traditional fungicide ketoconazole (KTZ).
研究领域:
纳米技术
·
生物医学工程
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药学
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微生物学
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中医
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）