Downregulation of Ambra1 by altered DNA methylation exacerbates dopaminergic neuron damage in a fenpropathrin-induced Parkinson-like mouse model.

Fenpropathrin (Fen), a volatile pyrethroid insecticide, is used widely for agricultural applications and has been reported to increase the risk of Parkinson's disease (PD). However, the molecular basis, underlying mechanisms, and pathophysiology of Fen-exposed Parkinsonism remain unknown. Recent studies have revealed epigenetic mechanisms underlying PD-related pathway regulation, including DNA methylation.

Small extracellular vesicles: a novel drug delivery system for neurodegenerative disorders.

Neurodegenerative diseases (NDs) have a slow onset and are usually detected late during disease. NDs are often difficult to cure due to the presence of the blood-brain barrier (BBB), which makes it difficult to find effective treatments and drugs, causing great stress and financial burden to families and society. Currently, small extracellular vesicles (sEVs) are the most promising drug delivery systems (DDSs) for targeted delivery of molecules to specific sites in the brain as a therapeutic vehicle due to their low toxicity, low immunogenicity, high stability, high delivery efficiency, high biocompatibility and trans-BBB functionality.

Early antidepressant treatment response prediction in major depression using clinical and TPH2 DNA methylation features based on machine learning approaches.

Objective: To identify DNA methylation and clinical features, and to construct machine learning classifiers to assign the patients with major depressive disorder (MDD) into responders and non-responders after a 2-week treatment into responders and non-responders.

Method: Han Chinese patients (291 in total) with MDD comprised the study population. Datasets contained demographic information, environment stress factors, and the methylation levels of 38 methylated sites of tryptophan hydroxylase 2 (TPH2) genes in peripheral blood samples.

microRNAs profiling of small extracellular vesicles from midbrain tissue of Parkinson's disease.

Small extracellular vesicles (sEVs) are generated by all types of cells during physiological or pathological conditions. There is growing interest in tissue-derived small extracellular vesicles (tdsEVs) because they can be isolated from a single tissue source. Knowing the representation profile of microRNA (miRNA) in midbrain tissue-derived sEVs (bdsEVs) and their roles is imperative for understanding the pathological mechanism and improving the diagnosis and treatment of Parkinson's disease (PD).

Multiple roles of neuronal extracellular vesicles in neurological disorders.

Neuropathy is a growing public health problem in the aging, adolescent, and sport-playing populations, and the number of individuals at risk of neuropathy is growing; its risks include aging, violence, and conflicts between players. The signal pathways underlying neuronal aging and damage remain incompletely understood and evidence-based treatment for patients with neuropathy is insufficiently delivered; these are two of the reasons that explain why neuropathy is still not completely curable and why the progression of the disease cannot be inhibited. Extracellular vesicles (EVs) shuttling is an important pathway in disease progression.

Identifying patients with major depressive disorder based on tryptophan hydroxylase-2 methylation using machine learning algorithms.

Objectives: This study aimed to identify patients with major depressive disorder (MDD) by developing different machine learning (ML) models based on tryptophan hydroxylase-2 (TPH2) methylation and environmental stress.

Methods: The data were collected from 291 patients with MDD and 100 healthy control participants: individual basic information, the Negative Life Events Scale (NLES) scores, the Childhood Trauma Questionnaire (CTQ) scores and the methylation level at 38 CpG sites in TPH2. Information gain was used to select critical input variables.

Comparison of the Variability of Small Extracellular Vesicles Derived from Human Liver Cancer Tissues and Cultured from the Tissue Explants Based on a Simple Enrichment Method.

A potential use of small extracellular vesicles (sEVs) for diagnostic and therapeutic purposes has recently generated a great interest. sEVs, when purified directly from various tissues with proper procedures, can reflect the physiological and pathological state of the organism. However, the quality of sEV is affected by many factors during isolation, including separation of sEV from cell and tissues debris, the use of enzymes for tissue digestion, and the storage state of tissues.

Short-term effect of fine particulate matter and ozone on non-accidental mortality and respiratory mortality in Lishui district, China.

Background: In recent years, air pollution has become an imminent problem in China. Few studies have investigated the impact of air pollution on the mortality of the middle-aged and elderly people. Therefore, this study aims to evaluate the impact of PM (fine particulate matter) and O (ozone) on non-accidental mortality and respiratory mortality of the middle-aged and elderly people in Lishui District of Nanjing and provide the evidence for potential prevention and control measures of air pollution.

Role of autophagy and oxidative stress to astrocytes in fenpropathrin-induced Parkinson-like damage.

Fenpropathrin is an insecticide that is widely used in agriculture. It remains unknown whether fenpropathrin exposure increases the risk of Parkinson's disease. We found that fenpropathrin increased oxidative stress both in vitro and in vivo.

Fenpropathrin induces degeneration of dopaminergic neurons via disruption of the mitochondrial quality control system.

The synthetic pyrethroid derivative, fenpropathrin, is a widely used insecticide. However, a variety of toxic effects in mammals have been reported. In particular, fenpropathrin induces degeneration of dopaminergic neurons and parkinsonism.

Generation of a Novel Mouse Model of Parkinson's Disease via Targeted Knockdown of Glutamate Transporter GLT-1 in the Substantia Nigra.

Parkinson's disease (PD) is a common neurodegenerative disease that is characterized by pathological dopaminergic (DA) neuronal death and α-synuclein aggregation. Glutamate excitotoxicity is a well-established pathogenesis of PD that involves dysfunctional expression of glutamate transporters. Glutamate transporter-1 (GLT-1) is mainly responsible for clearance of glutamate at synapses, including DA synapses.

Regulatory Mechanism of miR-543-3p on GLT-1 in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) features the degeneration and death of dopamine neurons in the substantia nigra pars compacta and the formation of Lewy bodies that contain α-synuclein. Among the numerous PD etiologies, glutamate excitotoxicity is a research hot spot, and glutamate transporters play key roles in this theory. It has been shown that the expression of the glutamate transporter is regulated by microRNAs.

β N-O turns and helices induced by β2-aminoxy peptides: synthesis and conformational studies.

Herein, we report an efficient route for the asymmetric synthesis of β(2)-aminoxy acids as well as experimental and theoretical studies of conformations of peptides composed of β(2)-aminoxy acids. The nine-membered-ring intramolecular hydrogen bonds, namely, β N-O turns, are generated between adjacent residues in those peptides, in accordance with our computational results. The presence of two consecutive homochiral β N-O turns leads to the formation of β N-O helical structures in solution, although both helical (composed of two β N-O turns of the same handedness) and reverse-turn (composed of two β N-O turns with opposite handedness) structures are of similar stability, as suggested by theoretical studies.

Disulfide bond creates a small connecting loop in aminoxy peptide backbone.

Disulfide-bond formation between the side chains of cysteine-cysteine pairs is often critical to the folding behavior, stability, and functionality of proteins. In this paper, we report that sulfur atoms can be introduced into the amide groups of aminoxy peptides to form a novel type of disulfide bridge, which creates a connecting loop in the peptide backbone.

[Features of heart rate, blood pressure, heart rate variability and cerebral blood flow during sequential head-up tilt test].

Objective: To investigate the features of BP, HR, cerebral blood flow (CBF) and heart rate variation (HRV) during sequential head-up tilt table test (HUT) and provide information for methodology of testing tendency to syncope in pilots.

Method: Sixteen healthy male were exposed to HUT +45 degrees 20 min, +60 degrees 20 min, and +75 degrees 20 min respectively with 5 min rests in between. CBFV, HR, HRV, BP were measured with transcranial doppler image (TCI), 12-Lead in phase ECG.