(133) Investigating Actinidin as a Potential Collagenase on Human Peyronie’s Disease Cells
Notice bibliographique
Résumé
Abstract Introduction Peyronie's Disease (PD) is characterized by a connective tissue disorder in the penile tunica albuginea and the formation of collagen-rich plaques, leading to penile curvature, painful erections, and erectile dysfunction. Intralesional Collagenase Clostridium histolyticum injections are no longer available in Canada, making treatment options for PD limited. Actinidin is a soluble enzyme that has the ability to hydrolyze various types of collagen and fibrinogen. We have previously reported the efficacy of actinidin on reducing collagen in in vitro human PD models. Objective To determine the dose-response efficacy and cytotoxicity of actinidin in reducing the intercellular bound collagen in human PD plaque models. Methods Fibroblast cells are isolated from human PD tissue (N ≥ 3) and 2D models are cultured. These cells were subjected to various treatment groups including media-only control and 5 concentrations of actinidin treatment ranging from 0.5 mg/ml to 30 mg/ml. The collagenase treatment was prepared from Hayward kiwi by isolating actinidin by filtration and pH adjustment. A dose-response curve was generated at different time points at various actinidin concentrations using an MTT assay. After 24 hours of treatment, collagen extraction was performed and quantified using a Soluble Collagen Quantification Assay Kit and a fluorescent microplate reader. The effects of the treatments on the extracellular matrix were further investigated by staining the cells with DAPI for the nucleus and Phalloidin-conjugated FITC for actin filaments. A twelve-hour timelapse was conducted using a fluorescent confocal microscope to capture FITC and DAPI fluorescein images. The total fluorescent area of each well was measured, and actin signals were normalized by the DAPI signals. Results The dose-response curve revealed that the lethal concentration affecting 50% of the cells after a 48-hour period is approximately 15-20 mg/ml. Treatment of 1 mg/mL actinidin significantly reduced cellular collagen of human PD fibroblasts compared to the control group (P < 0.001). The normalized stained β-actin signal was measured as the ratio between intracellular actin staining and nuclei count in each microscopic field. The high concentration actinidin treatment (30 mg/mL) exhibited a significantly higher normalized actin signal compared to other treatment groups (P < 0.0001). These findings suggest that actinidin may possess mechanisms that affect the plasma membrane integrity. Conclusions Our continuation of preliminary results demonstrates the ability of actinidin to break down PD cells by compromising extracellular collagen and the cellular membrane. High doses of actinidin cause cell destruction and we suggest that treatment should not exceed 10 mg/ml. Further studies will investigate the molecular mechanism of actinin in hydrolyzing collagen and to evaluate the effects on an animal model. Given the absence of durable FDA-approved treatments for PD in Canada, this novel option holds future treatment potential. Disclosure Yes, this is sponsored by industry/sponsor: KiwiEnzyme.com Ltd. Clarification: No industry support in study design or execution.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».