EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
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2024
·
IF 3.9
Junpu Li,Yan Guo
Background Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. Cryptococcal antigen (CrAg) testing from serum and cerebrospinal fluid (CSF) has been regarded as a gold standard for early diagnosis. This study aimed to develop and validate a rapid and sensitive sandwich chemiluminescent magnetic microparticle immunoassay (CMIA) for quantitative detection of CrAg in sera.Research design and methods CMIA is based on magnetic beads modified with capture antibodies and biotinylated antibodies and Streptavidin-polyHRP, where biotinylated antibodies functioned as the recognition element and Streptavidin-polyHRP as the signal component. Assay parameters were first optimized, and then assay performances were evaluated.Results Under optimized conditions, the total runtime of the CMIA was 22 min. The assay had a wide linear range (2 –10,000 ng/mL) and high analytical sensitivity (0.24 ng/mL), together with acceptable reproducibility, accuracy, and stability. Besides, it exhibited no cross-reactivity with other pathogens. Importantly, the assay showed 92.91% (95% CI, 80.97–93.02%) overall qualitative agreement with a commercial ELISA kit in a retrospective cohort of 55 cases with confirmed cryptococcal infection, and 72 controls without evidence of invasive fungal disease (IFD).Conclusion These results demonstrated that the present study paved a novel strategy for reliable quantitative detection of CrAg in sera.
研究领域:
医学微生物学
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免疫学
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临床诊断
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DOI
PubMed
高影响因子
MYCOLOGIA
·
2021
·
IF 2.696
Lili Wang,Min Zhang,Jian Guo,Wenzheng Guo,Ni Zhong,Hui Shen,Jinfeng Cai,Zhaoqin Zhu,Wenjuan Wu
Recently, Cryptococcus and non-albicans Candida (NAC) have emerged as health-threatening pathogens for clinical fungal infections. Due to their increased resistance to existing antifungal drugs, novel antifungals are urgently needed. In this study, we evaluated the antifungal effect of VT-1161 and its comparators itraconazole and fluconazole against common fluconazole-sensitive or -resistant Cryptococcus and NAC strains. The tested strains were obtained from Chinese patients by the Invasive Fungal Infection Group within the past 2 years. The minimum inhibitory concentrations (MICs) of VT-1161 and other triazoles were measured according to the Clinical and Laboratory Standards Institute (CLSI) M27-Ed4 guidelines. We found that VT-1161 exhibited strong in vitro activity against Cryptococcus spp.. VT-1161 (geometric mean MIC = 0.024 μg/mL) was 21.7-fold and 104.5-fold more potent than itraconazole and fluconazole, respectively. Against the seven Cryptococcus neoformans isolates with higher fluconazole MICs (≥8 μg/mL based on the MIC90 value of this azole), VT-1161 maintained potent activities, with MICs ranging between 0.031 and 0.5 μg/mL. For NAC spp., VT-1161 (geometric mean MIC = 0.099 μg/mL) was 6.0-fold and 11.4-fold more effective than itraconazole and fluconazole, respectively. There is a positive correlation of the MICs between VT-1161 and itraconazole/fluconazole. The MIC values of VT-1161 against Candida glabrata and Candida tropicalis were significantly lower than those of fluconazole, whereas for Candida parapsilosis the differences in the MIC values between VT-1161 and fluconazole were not statistically significant. The results showed that tetrazole VT-1161 might be a promising candidate for treating Cryptococcus and NAC infections.
研究领域:
医学
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微生物学
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药理学
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DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2025
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IF 11.9
Liting Cheng,Zhongyi Ma,Xinlin Yang,Xue Wang,Yuqiong Wang,Xinlong Liu,Zhongjie Tang,Dingxi Jang,Guojian Liao,Tongbao Liu,Shuang Wu,Chong Li
Cryptococcosis, a serious systemic fungal infection caused by Cryptococcus neoformans ( C. neoformans ) and its variants, poses a significant clinical challenge due to its poor prognosis and severe health implications. The treatment of cryptococcal infections is complicated by several unique factors, stemming from both the pathogenic characteristics of the fungi and the biological barriers they exploit. These include the fungi's protective capsule, their ability to reside within host macrophages—thereby evading pharmacological intervention—and their involvement in multi-organ infections such as the lung and brain, in particular their strategic positioning within the brain, protected by the blood-brain barrier (BBB). To overcome these obstacles, precise active targeting emerges as a pivotal strategy. Identifying common targets is imperative to enhance therapeutic efficacy while ensuring the druggability of delivery systems. However, research on the methodology for selecting such shared targets remains sparse. In our investigation, we have pioneered the use of secreted proteins as shared target to trace the pathogens and their infection pathways. We identified the mannoprotein Cig1, prominently expressed on the surfaces of infected macrophages, lungs, and brains, as a viable shared target. On this basis, we utilized Hemin, a ligand for Cig1, to design liposomes (Hemin Lip) tailored for addressing complex fungal infections. By leveraging the interaction with the secreted protein Cig1, Hemin Lip specifically identifies and binds to organs and macrophages harboring cryptococcal infections, thereby facilitating targeted and efficacious clearance of both intracellular and extracellular fungus. Moreover, we have extended this targeting mechanism to other nanomedicinal platforms, including albumin nanoparticles. This study proposes an innovative drug delivery model that targets extracellular secretory proteins within the infection microenvironment, offering a streamlined formulation with the potential for effective therapy against complex infections.
研究领域:
医学
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微生物学
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药理学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Chunsong Lu,Jie Liu,Lanlan Gan,Xiaoming Yang
Distinguishing the isomers is considered to be challenging, and shows the great importance in the biochemical and pharmaceutical fields. Herein, the blue carbon dots (CDs) were successfully raised on the basis of a facile hydrothermal way, since Cryptococcus served as the carbon source. Importantly, the as-prepared CDs were employed to achieve the differentiation and detection of two benzenediols. To be specific, the fluorescence of CDs was enhanced once m -benzenediol (resorcinol) was added, while introducing p -benzenediol (hydroquinone) lead to their fluorescence quenching. Towards the mechanism, the addition of m -benzenediol promoted the formation of hydrogen bonds between m -benzenediol and CDs, and thus resulting in their enhanced fluorescence. In contrast, the fluorescence quenching occurred due to the electron transferring from the rich-electrons of CDs to p -benzoquinone, when p -benzenediol was oxidized to be p -benzoquinone. Therefore, a differentiating strategy of two isomers has been proposed, and also contributed to detecting m -benzenediol and p -benzenediol concentrations in the ranges of 2 × 10 −3 to 1 × 10 −7 M and 2 × 10 -5 to 2 × 10 -9 M, respectively. Although there already existed the high performance liquid chromatography and other chemical methods for determining benzenediols, the current strategy provided a new way of distinguishing and assaying the isomers of benzenediols.
研究领域:
化学
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材料科学
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分析化学
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DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2022
·Vol. 414
·期 16
·4645-4654
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IF 4.478
Jiang Haixia,Liu Chunlong,Qu Qi,Wang Mengfan,Qi Wei,Peng Xin,He Zhimin
The surface-enhanced Raman scattering (SERS) technique has displayed a broad application prospect in disease diagnosis owing to its high sensitivity, fast responsiveness, and high specificity. In this study, we developed a SERS-based immunoassay for the detection of cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM), which is an important biomarker of cryptococcosis. The coupled localized surface plasmon resonance effect between magnetic SERS substrates and SERS tags gave rise to an enhanced Raman signal upon the formation of sandwich complexes, which contributes to the sensitive and specific detection of GXM. As a result, the developed method provided a lower limit of detection (1.25 ng/mL) than conventional methods, such as latex agglutination, lateral flow assay, and enzyme-linked immunosorbent assay. Additionally, a recovery experiment was performed to detect GXM in human serum, which also validated the potential advantages of a SERS-based immunoassay in the clinical diagnosis of cryptococcosis. Graphical abstract
研究领域:
医学诊断
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生物化学
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光谱学
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DOI
PubMed
高影响因子
TALANTA
·
2024
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IF 5.6
Xuelei Zang,Yangyu Zhou,Shuming Li,Gang Shi,Hengyu Deng,Xuefeng Zang,Jingrong Cao,Ruonan Yang,Xuwen Lin,Hui Deng,Yemei Huang,Chen Yang,Ningxin Wu,Chao Song,Lidong Wu,Xinying Xue
Cryptococcus is a pathogenic fungus that poses a threat to human health. Conventional detection methods have limited the rapid and accurate qualitative and quantitative analysis of Cryptococcus, affecting early diagnosis and treatment. In this study, we developed a Point-of-Care Testing (POCT) platform that integrates lateral flow immunoassay (LFIA) with smartphones, enabling both rapid qualitative and quantitative detection of Cryptococcus. The LFIA strip utilizes latex microspheres (LMs) as labeling probes, achieving a detection limit of 3000 CFU/mL and presenting higher sensitivity than the Colloidal Gold Nanoparticles Lateral Flow Immunoassay (AuNPs-LFIA) strip, and approximately eight times that of the AuNPs-LFIA strip. Additionally, it exhibiting no cross-reactivity with over 24 common pathogens and validated in clinical samples. For quantitative analysis, artificial intelligence algorithms were employed to convert smartphone-captured images into grayscale values. Eleven feature values were utilized as a dataset for machine learning to construct a linear regression model, with Mean Squared Error (MSE) and R 2 reaching 0.45 and 0.91, respectively. Moreover, the recovery rates in the serum samples ranged from 90.0 % to 108 %, indicating a good practicability. This research presents a rapid diagnostic technology for Cryptococcus and lays the theoretical and technical groundwork for detecting other pathogens.
研究领域:
医学诊断
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微生物学
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人工智能
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2020
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IF 7.727
Yanchao Liu,Yi Han,Ting Fang,Si-Min Chen,Xinyu Hu,Lijun Song,Hui Shen,Haiqing Dong,Yuan-Ying Jiang,Zui Zou,Yongyong Li,Mao-Mao An
As the gold standard treatment for invasive fungal infection , amphotericin B (AmB) is limited by its severe nephrotoxicity . It has been shown that AmB complex with albumin in vivo forms a sub-10 nm nanocomplex within kidney excretion size range and eventually induces the nephrotoxicity. This study presents an approach to take advantage of the “weakness” of such unique interaction between AmB and albumin to form AmB nanocomplex beyond the size range of kidney excretion. Herein, a novel strategy was developed by directly assembling molecular BSA into larger-sized nanostructures with the reconstructed intermolecular disulfide bond and hydrophobic interaction. The rich binding sites of AmB within BSA nanostructures enabled the efficient AmB loading and forming nanoparticle (AmB-NP) which exceeds the size range of kidney excretion (~ 60 nm). We found nanoassembly with BSA redirected biodistribution of AmB with a 2.8-fold reduction of drug accumulation in the kidney and significantly improved its renal impairment in mice. Furthermore, we found that nanoassembly with BSA significantly increased the biodistribution of AmB in brain and endowed it 100-folds increase in pharmacological effect against meningoencephalitis caused by common fungal pathogen Cryptococcus neoformans . Together, this study not merely overcomes the nephrotoxicity of AmB using its “weakness” by a nanoassembly method, and provides a new strategy for reducing toxicity of drugs with high albumin binding rate in vivo .
研究领域:
药理学
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纳米医学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2025
·Vol. 16
·期 1
·1-16
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IF 15.7
Bian Xufei,Guo Qian,Yau Lee-Fong,Yang Ling,Wang Xiaoyou,Zhao Shikang,Wu Shiqiong,Qin Xurong,Jiang Zhi-Hong,Li Chong
Lipid nanoparticles have shown success in targeting major organs such as the liver, spleen, and lungs, but crossing the blood-brain barrier (BBB) remains a major challenge. Effective brain-targeted delivery systems are essential for advancing gene therapy for neurological diseases but remain limited by low transport efficiency and poor nucleic acid stability. Here, we report a library of ionizable lipids based on the tetrahydroisoquinoline structure of protoberberine alkaloids, designed to improve BBB penetration via dopamine D3 receptor-mediated endocytosis. These nanoparticles offer three key advantages: enhanced brain uptake, improved nucleic acid stability through poly(A) self-assembly, and minimal immunogenicity with inherent neuroprotective properties. In murine models, they demonstrate therapeutic potential in Alzheimer’s disease, glioma, and cryptococcal meningitis. This berberine-inspired delivery system integrates precise receptor targeting with nucleic acid stabilization, offering a promising platform for brain-targeted therapeutics.
研究领域:
神经科学
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药物学
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基因治疗
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纳米技术
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DOI
PubMed
高影响因子
Microbiology Spectrum
·
2025
·Vol. 13
·期 8
·
IF 3.8
Tian Chen,Shaolan Liu,Fei Yang,Zhangxuan He,Menghua Tang,Lu Ge,Hongyi Zhang,Sijie Liu,Xiaolei Zhu,Mengqi Peng,Heng Zhang,Wenxu Cheng,Yi Sun
Invasive fungal infections and emerging antifungal resistance mediated by pathogenic fungi, notably Candida spp., Aspergillus spp., Cryptococcus neoformans, and Exophiala dermatitidis, pose a critical challenge to global public health systems. This study evaluated the synergistic antifungal activity of oleanolic acid (OA) combined with five azole agents (itraconazole [ITR], voriconazole [VOR], posaconazole [POS], isavuconazole [ISA], and fluconazole) against Candida spp., Aspergillus spp., E. dermatitidis, and C. neoformans. Using CLSI-compliant broth microdilution assays (M27-A3/M38-A2), we determined the minimum inhibitory concentrations (MICs) of oleanolic acid against four fungal pathogens and evaluated in vitro synergistic interactions with five azoles to assess their therapeutic potential. OA exhibited no intrinsic fungicidal activity when administered alone. However, synergistic inhibition was observed in specific azole combinations across tested pathogens: Candida spp. (n = 18) demonstrated 33% (6/18) and 56% (10/18) synergy rates with ITR and POS, respectively. Aspergillus spp. (n = 30) showed enhanced synergism at 80% (24/30) for ITR and 97% (29/30) for POS. All OA-azole combinations were synergistic against C. neoformans (n = 8), with rates of 75% (6/8) for ITR, 75% (6/8) for VOR, 87.5% (7/8) for ISA, and 100% (8/8) for POS. In contrast, E. dermatitidis (n = 21) responded only to OA/POS (52%, 11/21). Overall synergistic frequencies were POS (75%, 58/77) > ITR (47%, 36/77) > ISA (9%, 7/77) > VOR (8%, 6/77). The OA-azole combinations demonstrated significant reductions in azole MIC values and exhibited synergistic antifungal activity, particularly against Aspergillus spp. and C. neoformans. While the mechanistic basis of OA’s chemosensitization remains uncharacterized, its multi-target pharmacological profile underscores potential utility in combating antifungal resistance.
研究领域:
医学真菌学
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药理学
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微生物学
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抗菌素耐药性
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药物协同
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
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IF 12.479
Yi Han,Yanchao Liu,Xiaoyi Ma,Aijun Shen,Yiqiong Liu,Nopphon Weeranoppanant,Haiqing Dong,Yan Li,Tianbin Ren,Le Kuai,Bin Li,Maomao An,Yongyong Li
Chemotherapy-induced neutropenia, a symptom of neutrophil depletion, makes cancer patients highly susceptible to invasive fungal infection with substantial morbidity and mortality. To address the cryptococcal brain infection in this condition, this study attempts to arm neutrophils (NEs) with antibiotics to potentiate the antifungal capability of NEs. To allow effective integration, amphotericin B, a potent antibiotic, is assembled with albumin nanoparticles through hydrophobic and hydrogen-bond interactions to form [email protected] nanoparticles (A-NPs). The nutrient composition (albumin) and virus-like size (~40 nm) facilitate efficient uptake of A-NPs by NEs to construct the antibiotics-armed NEs. It is demonstrated that the armed NEs can maintain the intrinsic biological functions of NEs, such as cell viability and capacity of migration to an inflammatory site. In a neutropenic mouse model of brain fungal infection, the treatment with the armed NEs allows for preventing fungal invasion more effectively than that with the native NEs, without the apparent systemic toxicity. Such a synergistic anti-infection system maximizes the antifungal effects by taking advantage of NEs and antibiotics. It provides a potential NEs-mediated therapeutic approach for treating fungal infection caused by chemotherapy-induced neutropenia.
研究领域:
肿瘤学
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药理学
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纳米技术
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传染病学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED ORGANOMETALLIC CHEMISTRY
·
2022
·Vol. 36
·期 4
·e6587
·
IF 4.072
Dan Mo,Xun Song,Jiri Wu,Yogini Jaiswal,Yifu Guan,Yuzhen Zhang,Yunjun Shen,Hedong Bian
Metal complexes have been reported to possess excellent free radical scavenging and antimicrobial properties. In the present study, seven linear trinuclear complexes were synthesized based on bis Schiff base ligand and complexes 1 , 3 – 7 are reported for the first time. Their structure was characterized by IR spectroscopy and single crystal diffraction. BSA was used as carrier to hybridize the synthesized complexes to construct hybrid proteins. The interaction between metal complex and BSA was studied by UV–Vis spectrophotometry and fluorescence spectroscopy. Static quenching was the main mechanism identified for the interaction between metal complex and BSA. In the superoxide dismutase (SOD) activity test, IC 50 values of complexes and hybrid proteins range between 2.89 and 26.53 μM, with hybrid proteins demonstrating a stronger activity than the complexes. Among all the complexes studied, complex 5 exhibited the strongest inhibition against Candida albicans (MIC 12.5 μg ml −1 ) and Cryptococcus neoformans (MIC 6.5 μg ml −1 ).
研究领域:
无机化学
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生物化学
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药学
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微生物学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
·
2024
·
IF 4.9
Xinyuan Peng,Qingtao Kong,Qian Wei,Shilin Guo,Qiying Chen,Min Peng,Binyi An,Xiaoyu Wang,Chen Zhang,Hong Sang
Currently, the therapeutic effect on cryptococcal infection patients is hindered by toxicity and drug resistance, making it urgent to discover alternative antifungals. Calcium channel blockers, verapamil (VER), have shown effective antifungal effects in several fungi. Here, we found that VER has a significant antifungal effect on Cryptococcus neoformans ( C. neoformans ). Furthermore, VER has significant synergistic effects with multiple antifungals, even caspofungin (CAS). We confirmed that VER and CAS had a synergistic antifungal effect in the Galleria mellonella . We conducted in-depth research on the possible mechanism of the synergistic impact of VER and CAS. After treatment with VER, the chitosan content of C. neoformans ' cell wall decreased and in dopamine liquid culture medium, we observed the leakage of melanin. Through cell wall fluorescence staining and stress sensitivity analysis, we further demonstrated that VER impaired the integrity of the C. neoformans ' cell wall. Another side, VER+CAS modification of C. neoformans membrane permeability, leading to intracellular ROS accumulation and mitochondrial membrane potential changes. VER eliminated the cytoplasmic calcium fluctuations caused by CAS stimulation and down-regulated the genes expression associated with the calcineurin pathway. In addition, we found that the enzyme activity of chitin deacetylase of C. neoformans is significantly influenced by the presence of Ca 2+ , suggesting that the use of VER may affect the activity. In summary, the synergistic antifungal effect of VER and CAS makes them effective and promising candidates for fungal treatment.
研究领域:
微生物学
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药理学
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医学真菌学
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传染病学
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产品关联
DOI
PubMed
高影响因子
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