Histatin–Photodynamic Therapy for Polyene-Resistant Biofilms in a 3D Model
Bibliographic record
Abstract
Oral candidiasis is primarily caused by Candida albicans ; however, bacteria such as Streptococcus mutans can also coexist and cooperate within the same biofilm. This study evaluated the combined effects of Histatin 3 (His3) and Histatin 5 (His5) with antimicrobial photodynamic therapy (aPDT) using a 3-dimensional oral epithelium model infected with mixed biofilms of C. albicans (polyene-resistant strains) and S. mutans . The tissues, divided into groups (His3 + aPDT, His5+aPDT, His3, His5, or aPDT), were first treated with the salivary proteins His3 or His5 (2 h, 37 °C, 60 rpm/min) followed by infection with mixed biofilms. After 24 h of biofilm formation, aPDT was applied (PDZ: 200 mg/L; LED light: 660 nm with 50 J/cm²) using intermittent irradiation cycles ( n = 9/group). Biofilm viability (CFU/mL), total proteins (intracellular and extracellular), and proteomic analysis were performed. Biocompatibility and tissue invasion were also assessed by MTT assays and histological analysis, respectively. His3+aPDT and His5+aPDT reduced mixed biofilm viability by 67% ( P = 0.0038) and 65% ( P = 0.0062), respectively. His3 and His5 alone promoted a 35% to 45% ( P = 0.018; P = 00.24) reduction, while aPDT alone reduced by 50% to 55% ( P = 0.022; P = 0.037). Combined treatments enhanced efficacy by ~30% compared with individual treatments. Histological evaluation also confirmed reduced biofilm penetration and hyphal formation, particularly with His5+aPDT. Proteomic analysis of the proteins from C. albicans revealed the downregulation of structural and transport proteins, which can likely weaken the biofilm. The combination of His3 and His5 with aPDT enhances antimicrobial efficacy against resistant multispecies biofilms while maintaining biocompatibility. By reducing biofilm viability and compromising proteins, this approach provides a promising alternative for treating oral candidiasis associated with polyene-resistant C. albicans species.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".