Objective: The global rise in the resistance of to conventional antifungals makes infections harder to treat. The main objective of this study was to investigate the antifungal effects and underlying mechanisms of leflunomide in combination with triazoles against resistant .
Methods: In this study, the microdilution method was used to determine the antifungal effects of leflunomide in combination with three triazoles on planktonic cells in vitro. The morphological transition from yeast to hyphae was observed under a microscope. The effects on ROS, metacaspase, efflux pumps, and intracellular calcium concentration were investigated, respectively.
Results: Our findings suggested that leflunomide + triazoles showed a synergistic effect against resistant in vitro. Further study concluded that the synergistic mechanisms were resulted from multiple factors, including the inhibited efflux of triazoles, the inhibition of yeast-to-hyphae transition, ROS increasing, metacaspase activation, and [Ca] disturbance.
Discussion: Leflunomide appears to be a potential enhancer of current antifungal agents for treating candidiasis caused by resistant . This study can also serve as an example to inspire the exploration of new approaches to treating resistant .
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http://dx.doi.org/10.2147/IDR.S415229 | DOI Listing |
PeerJ
January 2025
Department of Dental Materials, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
Background: Periodontitis is not always satisfactorily treated with conventional scaling and root planing, and adjunctive use of antibiotics is required in clinical practice. Therefore, it is important for clinicians to understand the diversity and the antibiotic resistance of subgingival microbiota when exposed to different antibiotics.
Materials And Methods: In this study, subgingival plaques were collected from 10 periodontitis patients and 11 periodontally healthy volunteers, and their microbiota response to selective pressure of four antibiotics (amoxicillin, metronidazole, clindamycin, and tetracycline) were evaluated through 16S rRNA gene amplicon and metagenomic sequencing analysis.
Front Oncol
January 2025
Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Introduction: Small cell lung cancer (SCLC) is characterized by significant heterogeneity and plasticity, contributing to its aggressive progression and therapy resistance. Autophagy, a conserved cellular process, is implicated in many cancers, but its role in SCLC remains unclear.
Methods: Using a genetically engineered mouse model ( ; ; GFP-LC3-RFP-LC3△G), we tracked autophagic flux to investigate its effects on SCLC biology.
Oncol Lett
March 2025
College of Pharmacy, Korea University, Sejong 30019, Republic of Korea.
Cancer stem cells (CSCs) contribute to the resistance of intractable prostate cancer, and dopamine receptor (DR)D2 antagonists exhibit anticancer activity against prostate cancer and CSCs. Human prostate cancer PC-3 cells were used to generate CSC-like cells, serving as a surrogate system to identify the specific DR subtype the inhibition of which significantly affects prostate-derived CSCs. Additionally, the present study aimed to determine the downstream signaling molecules of this DR subtype that exert more profound effects compared with other DR subtypes.
View Article and Find Full Text PDFIndian Dermatol Online J
December 2024
Department of Microbiology, Yenepoya Medical College, (Deemed to be University), Mangalore, Karnataka, India.
Background: The widespread occurrence of chronic and recurrent dermatophytosis has significantly affected the quality of life for patients in India and beyond. Identifying the causative dermatophytes and understanding their antifungal susceptibility can aid clinicians in tailoring effective antifungal therapies.
Materials And Methods: Patients with chronic and recurrent dermatophytosis were enrolled, and conventional fungal cultures were conducted on skin scrapings.
NIHR Open Res
January 2025
Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, England, L69 7BE, UK.
Background: PROTECT ( Platform Randomised evaluation of clinical Outcomes using novel TEChnologies to optimise antimicrobial Therapy) has brought together a team of researchers to design a platform trial to rapidly evaluate and adopt into care multiple diagnostic technologies, bringing immediate benefit to patients. Rapid diagnostic tests will be used to identify patients at risk of deterioration from severe infection, before they become critically unwell. The platform will assess their comparative clinical effectiveness and cost-effectiveness relative to current standard of care.
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