Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

Effects of topical applications of porcine acellular urinary bladder matrix and Centella asiatica extract on oral wound healing in a rat model.

OBJECTIVES: To evaluate the effects of topical applications of porcine acellular urinary bladder matrix (AUBM) and Centella asiatica extract (CAE) on the healing of tongue wounds in a rat model. MATERIALS AND METHODS: Wounds were made in the tongue using a punch tool in 64 male Sprague-Dawley rats, randomized into four groups (n = 16 per group): group 1 (control), group 2 (CAE), group 3 (AUBM mixed with orabase), and group 4 (orabase). No product was applied in group 1 and groups 2-4 received three daily topical applications. The animals were weighed on day 0 and at the time of euthanasia. Four rats in each group were euthanized at days 2, 7, 14, and 21 and the tongues were processed for: macroscopic morphometric analysis, myeloperoxidase (MPO) and malondialdehyde (MDA) levels, histological wound repair (degree of reepithelialization and inflammation), and CD31 positivity. RESULTS: The animals' weight gain, histological wound repair, and CD31 positivity from greatest to least were: AUBM > CAE > orabase > control. Percentage of tongue occupied by wound, MPO, and MPA levels from least to greatest were: AUBM < CAE < orabase < control, whereby the AUBM group showed significant differences (p ≤ 0.05) in comparison with the other groups on days 2, 7, 14, and 21 for percentage of tongue occupied by wound and MDA and on days 7, 14, and 21 for MPO. CONCLUSIONS: CAE is effective for oral tissue regeneration, while AUBM is an even more potent means of oral mucosa regeneration. CLINICAL RELEVANCE: AUBM may be beneficial to patients with oral wounds; this finding requires further clinical and laboratory investigation.