Multi-technology integrated network pharmacology-based study on phytochemicals, active metabolites, and molecular mechanism of Psoraleae Fructus to promote melanogenesis.

Ethnopharmacological Relevance: According to the Compendium of Materia Medica (Shizhen Li, Ming dynasty) and Welfare Pharmacy (Song dynasty), Psoraleae Fructus (PF), a traditional Chinese medicine (TCM) has a bitter taste and warm nature, which has the effect of treating spleen and kidney deficiency and skin disease. Although PF has been widely used since ancient times and has shown satisfactory efficacy in treating vitiligo, the active substances and the mechanism of PF in promoting melanogenesis remain unclear.

Aim Of The Study: To explore the active substances and action mechanisms of PF in promoting melanogenesis.

Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study.

Introduction: Sleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders.

Methods: We used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations.

Exosomes rich in Wnt5 improved circadian rhythm dysfunction via enhanced PPARγ activity in the 6-hydroxydopamine model of Parkinson's disease.

Sleep disorder is one of the most common non-motor symptoms in Parkinson's disease (PD) and even appear as early symptoms. Here we investigated the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-EXOs) on sleep disorder in PD rats. 6-hydroxydopa (6-OHDA) was used to establish the PD rat model.

Optic Nerve Sheath Fenestration for Progressive Visual Loss in Cerebral Venous Sinus Thrombosis: A Long-Term Retrospective Observational Study.

Introduction: Progressive cerebral venous sinus thrombosis (CVST)-induced visual loss remains problematic, despite decreasing overall mortality owing to early diagnosis and aggressive treatment. Optic nerve sheath fenestration (ONSF) improves or stabilizes visual function in patients with idiopathic intracranial hypertension; however, its role in CVST awaits elucidation. We evaluated the efficacy and safety of ONSF in resolving CVST-induced visual impairment based on long-term observation.

Mesenchymal stem cell-derived exosomes altered neuron cholesterol metabolism via Wnt5a-LRP1 axis and alleviated cognitive impairment in a progressive Parkinson's disease model.

Parkinson's disease (PD) is associated with abnormal metabolism of brain cholesterol, and the metabolites of neuronal cholesterol may also affect neurodegenerative progression. In this study, we aim to explore the therapeutic effect of BMSC derived exosomes on motor and cognitive deficits in α-synuclein (α-Syn) A53T transgenic mice, a progressive PD animal model. Results revealed that rotating rod performance of α-Syn A53T TG mice decreased by 45.

Cerebrospinal Fluid Extracellular Vesicles with Distinct Properties in Autoimmune Encephalitis and Herpes Simplex Encephalitis.

Encephalitis mediated by autoantibodies against neuronal antigens and herpes simplex encephalitis (HSE) are seemingly separate causes of encephalopathy in adults. Autoimmune encephalitis (AE) is autoimmune in origin, and herpes simplex encephalitis is infectious. The purpose of this study was to examine the role of cerebrospinal fluid (CSF) exosomes from patients with antibody-positive AE and HSE.

Exosomes isolated during dopaminergic neuron differentiation suppressed neuronal inflammation in a rodent model of Parkinson's disease.

Our previous investigation showed Wnt signal pathway was significantly activated during DA neuron differentiation of epiblast-derived stem cells. In this study, we next attempt to examine the therapeutic potential of the purified exosomes derived bone marrow mesenchymal stem cells (BMSCs) by administrating exosomes into the rat striatum of parkinson's disease (PD) animal model. Results revealed that the protein levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α), and reactive oxygen species (ROS) in the substantia nigra of PD rats were down regulated after injection of BMSC induced-Exosomes into the striatum of PD model compared to BMSC quiescent-Exosomes.

The Efficacy of High- or Low-Frequency Transcranial Magnetic Stimulation in Alzheimer's Disease Patients with Behavioral and Psychological Symptoms of Dementia.

Introduction: Alzheimer's disease (AD) is usually accompanied by different degrees of behavioral and psychological symptoms of dementia (BPSD). Transcranial magnetic stimulation (TMS) has been applied for the treatment of AD as a painless and noninvasive therapy. However, the efficacy of repetitive TMS (rTMS) with different frequencies in AD with BPSD remains unknown.

Neuroprotective Effect of Trans-Resveratrol in Mild to Moderate Alzheimer Disease: A Randomized, Double-Blind Trial.

Introduction: Amyloid-beta (Aβ) protein is a major component of the extracellular plaque found in the brains of individuals with Alzheimer's disease (AD). In this study, we investigated the effect of trans-resveratrol as an antagonist treatment for moderate to mild AD, as well as its safety and tolerability.

Methods: This was a case-control study that enrolled 30 selected patients who had been clinically diagnosed with moderate to mild AD.

Altered microRNAs in cerebrospinal fluid exosomes in paraneoplastic and autoimmune encephalitis: A possible feedback in cancer development.

Aims: The purpose of this study was to examine the role of cerebrospinal fluid (CSF) exosomes from patients with paraneoplastic and autoimmune encephalitis (AE).

Main Methods: Towards this, microRNA profiling in the exosomes which were isolated from cerebrospinal fluid of 12 patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, 12 patients with anti-gamma-aminobutyric acid-B (GABA) receptor encephalitis, 12 patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and 12 patients with anti-contactin-associated protein-like 2 (CASPR2) encephalitis, and 12 control individuals negative of antibodies against neuronal auto-antigens. Selected findings were validated with quantitative RT-PCR.

Recent Advances on Extracellular Vesicles in Central Nervous System Diseases.

Extracellular vesicles (EVs) are particles released by multiple cells, encapsulated by lipid bilayers and containing a variety of biological materials, including proteins, nucleic acids, lipids and metabolites. With the advancement of separation and characterization methods, EV subtypes and their complex and diverse functions have been recognized. In the central nervous system (CNS), EVs are involved in various physiological and pathological processes, such as regulation of neuronal firing, synaptic plasticity, formation and maintenance of myelin sheath, propagation of neuroinflammation, neuroprotection, and spread and removal of toxic protein aggregates.

Exosomes expressing neuronal autoantigens induced immune response in antibody-positive autoimmune encephalitis.

The immunological role of exosomes in autoimmune encephalitis (AE) remains uncharacterized and not examined. In this study we ought to determine whether exosomes are generated in AE and to define the presence of cell surface neuronal autoantigens (autoAgs) in the cargo. Exosomes were isolated from cerebrospinal fluid (CSF) from 12 patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, 8 patients with anti-gamma-aminobutyric acid-B (GABA) receptor encephalitis, 8 patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, 8 patients with anti-contactin-associated protein-like 2 (CASPR2) encephalitis, 10 patients with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1,2 (AMPA) receptor encephalitis and 30 control individuals negative of antibodies against neuronal autoAgs.

Differential Expression of microRNA Profiles and Signals in Stem Cell-Derived Exosomes During Dopaminergic Neuron Differentiation.

The role of secreted exosomes during dopaminergic (DA) neuron differentiation is still unknown. To investigate the roles of exosomes in DA neuron fate specification, we profiled exosomal microRNAs (miRNAs) during DA neuron differentiation of epiblast-derived stem cells (EpiSCs). There were 26 miRNAs differentially expressed (relative fold >2,  < 0.

Application of Neck Circumference in Four-Variable Screening Tool for Early Prediction of Obstructive Sleep Apnea in Acute Ischemic Stroke Patients.

Background: The purpose of this study was to validate and pilot the use of the four-variable screening tool (4V) and modified 4V tools to identify acute ischemic stroke and transient ischemic attack (TIA) patients at high risk of obstructive sleep apnea (OSA).

Methods: Two modified scales, 4V-1 (ie, using neck circumference instead body mass index, regardless of gender) and 4V-2 (ie, as above but scored differently according to gender) were designed. These tools were used in a consecutive cohort of 124 acute ischemic stroke/TIA patients, together with the 4V-1, 4V-2, 4V, as well as the STOP-BANG, the Berlin questionnaire, and the Epworth Sleepiness Scale (ESS).

Characterization of the 18 kDa translocator protein (TSPO) expression in post-mortem normal and Alzheimer's disease brains.

The 18 kDa translocator protein (TSPO) is a widely used target for microglial PET imaging radioligands, but its expression in post-mortem normal and diseased human brain is not well described. We aimed at characterizing the TSPO expression in human control (CTRL) and Alzheimer's disease (AD) brains. Specifically, we sought to: (1) define the cell type(s) expressing TSPO; (2) compare tspo mRNA and TSPO levels between AD and CTRL brains; (3) correlate TSPO levels with quantitative neuropathological measures of reactive glia and AD neuropathological changes; and (4) investigate the effects of the TSPO rs6971 SNP on tspo mRNA and TSPO levels, glial responses and AD neuropathological changes.

Using Extracellular Circulating microRNAs to Classify the Etiological Subtypes of Ischemic Stroke.

There is no effective biological method to classify ischemic stroke subtypes. In this study, we first performed a systematical gene array study on serum microRNAs with different ischemic stroke subtypes including 13 normal control subjects (NCs) and 87 ischemic stroke (IS) patients including 23 cardioembolism (CARD), 26 large artery atherosclerosis (LAA), 27 lacunar infarct (LAC), and 11 stroke of undetermined etiology (SUE). Validation was performed by using an independent cohort of 20 NCs and 85 IS patients including 28 CARD, 23 LAA, 18 LAC, and 16 SUE.

NFE2L2 variations reduce antioxidant response in patients with Parkinson disease.

Oxidative stress has been recognized as a risk factor of Parkinson's disease (PD) development. We hypothesized that decreased function of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-antioxidant response element (ARE) pathway might predispose to Parkinsonism. A case-control study was performed between NFE2L2 Single Nucleotide Polymorphism (SNP) and PD in a cohort of 765 unrelated patients with diagnosis of PD and 489 matched normal individuals.

Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease.

The differential diagnosis of Parkinson's diseases (PD) is challenging, especially in the early stages of the disease. We developed a microRNA profiling strategy for exosomal miRNAs isolated from cerebrospinal fluid (CSF) in PD and AD. Sixteen exosomal miRNAs were up regulated and 11 miRNAs were under regulated significantly in PD CSF when compared with those in healthy controls (relative fold > 2, p < 0.

Evidence for polymerase gamma, POLG1 variation in reduced mitochondrial DNA copy number in Parkinson's disease.

Background: It remains unclear whether the mtDNA content is related to the clinicopathological prognosis in Parkinson's disease (PD).

Methods/results: We analyzed the copy number of mtDNA using quantitative real-time PCR in 414 cases with PD and 231 healthy subjects from mainland of China. The level of mtDNA was significantly decreased in PD patients' peripheral blood as compared to that of healthy controls (p < 0.

Association of mitochondrial DNA polymerase γ gene POLG1 polymorphisms with parkinsonism in Chinese populations.

Background: Mitochondrial DNA polymerase gamma (POLG1) mutations were associated with levodopa-responsive Parkinsonism. POLG1 gene contains a number of common nonsynonymous SNPs and intronic regulatory SNPs which may have functional consequences. It is of great interest to discover polymorphisms variants associated with Parkinson's disease (PD), both in isolation and in combination with specific SNPs.

Cognitive impairment and the associated risk factors among the elderly in the Shanghai urban area: a pilot study from China.

Objectives: Our study aimed to investigate the prevalence of cognitive impairment(CI) and the associated risk factors among elderly people in Shanghai urban area, China.

Methods: A population-based survey was conducted among people aged 55 years or older in urban areas of Shanghai. Face-to-face interviews were carried out to collect information including demographic characteristics, medical history, and medication use, etc.

Four novel rare mutations of PLA2G6 in Chinese population with Parkinson's disease.

Background: Mutations in the phospholipase A2 Group 6 (PLA2G6) gene have been identified in autosomal recessive neurodegenerative diseases classified as infantile neuroaxonal dystrophy and neurodegeneration with brain iron accumulation. Recently, PLA2G6 was also reported as the causative gene for early-onset PARK14-linked dystonia-parkinsonism.

Methods/results: To address whether PLA2G6 mutations are also an important cause of PD, we screened sequence variants of PLA2G6 in 250 PD patients and 550 controls in a Chinese Han populations.

Glyphosate induced cell death through apoptotic and autophagic mechanisms.

Herbicides have been recognized as the main environmental factor associated with human neurodegenerative disorders such as Parkinson's disease(PD). Previous studies indicated that the exposure to glyphosate, a widely used herbicide, is possibly linked to Parkinsonism, however the underlying mechanism remains unclear. We investigated the neurotoxic effects of glyphosate in differentiated PC12 cells and discovered that it inhibited viability of differentiated PC12 cells in dose-and time-dependent manners.

Extracellular signal-regulated kinase is involved in alpha-synuclein-induced mitochondrial dynamic disorders by regulating dynamin-like protein 1.

Compounding evidence suggests that alpha-synuclein (SNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) by inducing neurotoxicity. Mitochondria are highly dynamic organelles that undergo fusion and fission processes, the imbalance of which has been viewed as a key trigger for PD. However, the underlying relationship between SNCA and mitochondrial dynamics remains unclear.