Post-surgical Pyoderma Gangrenosum Following Elective Aesthetic Procedures: A Case Series of 10 Patients and a Multidisciplinary Treatment Approach.

Parkinson's disease (PD), one of the most prevalent neurodegenerative disorders worldwide, is clinically characterized by progressive motor symptoms of bradykinesia, rigidity, resting tremor, and postural instability. Neuropathologically, PD is defined by two hallmark features: the emergence of alpha-synuclein (-syn) positive inclusion bodies, termed Lewy pathology, and degeneration of dopaminergic neurons in the substantia nigra (SN), accompanied by reduced dopamine (DA) levels. The pathogenesis of PD is driven by multiple interconnected mechanisms, including neuroinflammation, oxidative stress, -syn aggregation, mitochondrial dysfunction, ferroptosis, disrupted calcium homeostasis, and gut microbiota dysbiosis, of which mitochondrial dysfunction has been identified as a core factor in PD. Mitochondria serve as critical regulators of cellular survival through ATP synthesis, calcium buffering, apoptotic signaling, and neurotransmitter recycling, , . Given the exceptionally high bioenergetic demands of neurons, mitochondrial impairment is increasingly recognized as a common denominator in various neurological disorders, , . Especially, mitochondria hold a distinctive position in PD for several other reasons. First, the current neurotoxin-induced models of PD rely on mitochondrial impairment to reproduce PD-like symptoms. Neurotoxins like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone trigger the death of dopaminergic neurons in humans and rats by directly inhibiting mitochondrial complex I activity. Second, mutations in PD-associated genes (, , , and ) directly impair mitochondrial quality control pathways, , . Third, clinical studies have identified various mitochondrial impairments in PD, including decreased mitochondrial numbers, imbalanced dynamics, decreased mitochondrial membrane potential (MMP), disrupted cristae structure, reduced respiratory capacity, and lowered ATP production. Moreover, therapeutic approaches targeting mitochondrial proteins or inhibiting mitochondrial damage have been shown to alleviate neuropathological features in PD animal models and patient-derived cells, highlighting the potential of enhancing mitochondrial function as a promising treatment strategy for PD. Mitochondria are organized in a highly dynamic tubular network that undergoes continuous remodeling through fusion and fission. This dynamic process not only controls mitochondrial morphology but also regulates their function and subcellular distribution. Disruptions in either fusion or fission impair mitochondrial mobility, reduce energy production, and increase oxidative stress, ultimately leading to cellular dysfunction and death. Mitochondrial fission is regulated by dynamin-1-related protein (DRP1), , , where Ser 616 phosphorylation promotes the translocation of DRP1 from the cytosol to mitochondria, while Ser 637 phosphorylation reverses this process. The fusion process is governed by mitofusin-1/2 (MFN1/2) and optic atrophy 1 (OPA1), which mediate outer and inner membrane fusion, respectively. Accumulating evidence from both toxin-induced and genetic models of PD supports the involvement of imbalanced mitochondrial dynamics and dysfunction in PD pathogenesis. Parkinsonian neurotoxins, such as 6-hydroxydopamine (6-OHDA), rotenone, and MPTP, have been shown to trigger mitochondrial fragmentation, culminating in the degeneration of dopaminergic neurons , , . Fibroblasts derived from PD patients with or mutations exhibit a more fragmented mitochondrial network, , . These observations strengthen the role of imbalanced mitochondrial fusion and fission in PD pathogenesis and highlight the potential of targeting mitochondrial dynamics with small molecules as a therapeutic strategy to modulate disease progression. Rhynchophylline (Rhy) is a plant-derived tetracyclic oxindole alkaloid isolated from species. Experimental evidence indicates that Rhy exhibits blood–brain barrier permeability, , , laying a solid foundation for its neuroprotective properties. Multiple studies have elucidated a broad spectrum of neuropharmacological activities associated with Rhy, including anti-addiction, anticonvulsant, sedative, and anti-anxiety, , . In particular, emerging studies have demonstrated the neuroprotective effects of Rhy in an MPTP-induced subacute PD mouse model, but the underlying molecular mechanism remains unclear. Recently, indole alkaloids have emerged as structural/functional classes of mitochondrial modulators, and we previously observed that the alkaloid fraction from (predominantly indole alkaloids) enhances mitochondrial fusion, prompting the present investigation into whether Rhy exerts protective effects on mitochondrial dynamics and the underlying mechanisms.