RESUMO
BACKGROUND: The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. METHODS: Adult female mice aged 8-10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. RESULTS: In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART's therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. CONCLUSIONS: At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Artesunato , Modelos Animais de Doenças , Fármacos Neuroprotetores , Proteínas Quinases , Animais , Artesunato/farmacologia , Artesunato/uso terapêutico , Camundongos , Feminino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Encefalite Antirreceptor de N-Metil-D-Aspartato/patologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Proteínas Quinases/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurônios/metabolismo , Microscopia Eletrônica de Transmissão , Mitofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Hipocampo/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismoRESUMO
We study a time dependent partial differential equation (PDE) which arises from classic models in ecology involving logistic growth with Allee effect by introducing a discrete weak solution. Existence, uniqueness and stability of the discrete weak solutions are discussed. We use bivariate splines to approximate the discrete weak solution of the nonlinear PDE. A computational algorithm is designed to solve this PDE. A convergence analysis of the algorithm is presented. We present some simulations of population development over some irregular domains. Finally, we discuss applications in epidemiology and other ecological problems.
Assuntos
Vetores de Doenças , Fenômenos Ecológicos e Ambientais , Modelos Teóricos , Controle de Mosquitos , Animais , Culicidae , Densidade DemográficaRESUMO
OBJECTIVES: The objective of this study was to determine the relative efficacy of irradiation using a device containing a far-infrared emitting ceramic powder (cFIR) for the management of chronic myofascial neck pain compared with a control treatment. DESIGN: This was a randomized, double-blind, placebo-controlled pilot study. PARTICIPANTS: The study comprised 48 patients with chronic, myofascial neck pain. INTERVENTION: Patients were randomly assigned to the experimental group or the control (sham-treatment) group. The patients in the experimental group wore a cFIR neck device for 1 week, and the control group wore an inert neck device for 1 week. MAIN OUTCOME MEASUREMENT: Quantitative measurements based on a visual analogue scale (VAS) scoring of pain, a sleep quality assessment, pressure-pain threshold (PPT) testing, muscle tone and compliance analysis, and skin temperature analysis were obtained. RESULTS: Both the experimental and control groups demonstrated significant improvement in pain scores. However, no statistically significant difference in the pain scores was observed between the experimental and control groups. Significant decreases in muscle stiffness in the upper regions of the trapezius muscles were reported in the experimental group after 1 week of treatment. CONCLUSIONS: Short-term treatment using the cFIR neck device partly reduced muscle stiffness. Although the differences in the VAS and PPT scores for the experimental and control groups were not statistically significant, the improvement in muscle stiffness in the experimental group warrants further investigation of the long-term effects of cFIR treatment for pain management.