Inhibition of MLKL-dependent necroptosis via downregulating interleukin-1R1 contributes to neuroprotection of hypoxic preconditioning in transient global cerebral ischemic rats.

Background: Our previous study indicated that hypoxic preconditioning reduced receptor interacting protein (RIP) 3-mediated necroptotic neuronal death in hippocampal CA1 of adult rats after transient global cerebral ischemia (tGCI). Although mixed lineage kinase domain-like (MLKL) has emerged as a crucial molecule for necroptosis induction downstream of RIP3, how MLKL executes necroptosis is not yet well understood. In this study, we aim to elucidate the molecular mechanism underlying hypoxic preconditioning that inactivates MLKL-dependent neuronal necroptosis after tGCI.

UNC13B variants associated with partial epilepsy with favourable outcome.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing.

Correlation of Seizure Increase and COVID-19 Outbreak in Adult Patients with Epilepsy: Findings and Suggestions from a Nationwide Multi-centre Survey in China.

Objectives: To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.

Methods: This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic.

Nurses' knowledge and attitudes towards palliative care and death: a learning intervention.

Background: In many countries, nurses are ill-prepared to provide care to patients with terminal illnesses. Limited education and training affect their ability to deliver proper palliative care. Only a few studies have explored appropriate and effective training methods of palliative care in China.

Neuregulin 1/ErbB4 signaling contributes to the anti-epileptic effects of the ketogenic diet.

Background: The ketogenic diet (KD) has been recognized as a potentially effective therapy to treat neuropsychiatric diseases, including epilepsy. Previous studies have indicated that KD treatment elevates γ-Amino butyric acid (GABA) levels in both human and murine brains, which presumably contributes to the KD's anti-seizure effects. However, this has not been systematically investigated at the synaptic level, and the underlying molecular mechanisms remain to be elucidated.

Kallistatin Inhibits Anoikis Resistance and Metastasis of Ectopic Endometrium Cells by Modulating MnSOD and Caspase 3 Signaling.

Endometriosis (EM) is a disease that involves active endometrial cell invasion and migration which is an important reason for infertility. Anoikis resistance is the most important prerequisite for EM, but the molecular mechanism is not yet clear. Kallistatin (KS) is one kind of serine protease inhibitors which had extensive biological function including anti-inflammatory, antioxidant stress, anti-angiogenesis, and anti-tumor.

Ilepcimide inhibited sodium channel activity in mouse hippocampal neurons.

Ilepcimide (ICM), a clinically effective antiepileptic drug, has been used in China for decades; however, its antiepileptic mechanism remains unclear. ICM is structurally similar to antiepileptic drug lamotrigine (LTG). LTG exerts its anticonvulsant effect by inhibiting voltage-gated Na channel (Na) activity.

Targeting the NCOA3-SP1-TERT axis for tumor growth in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate and lacks an effective therapeutic target. Elevated expression of human telomerase reverse transcriptase (TERT) is an important hallmark in cancers, but the mechanism by which TERT is activated differentially in cancers is poorly understood. Here, we have identified nuclear receptor coactivator-3 (NCOA3) as a new modulator of TERT expression and tumor growth in HCC.

Variants Associated Malformations of Cortical Development and Focal Epilepsy With Febrile Seizure Plus/Febrile Seizures: The Role of Molecular Sub-Regional Effect.

To explore the phenotype spectrum of variants and the possible mechanisms underlying phenotypical variation, we performed targeted next-generation sequencing in 305 patients with focal epilepsies and 91 patients with generalized epilepsies. Protein modeling was performed to predict the effects of missense mutations. All previously reported epilepsy-related variants were reviewed.

Knockout of PINK1 altered the neural connectivity of Drosophila dopamine PPM3 neurons at input and output sites.

Impairment of the dopamine system is the main cause of Parkinson disease (PD). PTEN-induced kinase 1 (PINK1) is possibly involved in pathogenesis of PD. However, its role in dopaminergic neurons has not been fully established yet.

Endoplasmic reticulum retention and degradation of a mutation in SLC6A1 associated with epilepsy and autism.

Mutations in SLC6A1, encoding γ-aminobutyric acid (GABA) transporter 1 (GAT-1), have been recently associated with a spectrum of epilepsy syndromes, intellectual disability and autism in clinic. However, the pathophysiology of the gene mutations is far from clear. Here we report a novel SLC6A1 missense mutation in a patient with epilepsy and autism spectrum disorder and characterized the molecular defects of the mutant GAT-1, from transporter protein trafficking to GABA uptake function in heterologous cells and neurons.

Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD.

Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B mouse model of ASD. Male and female Shank3B mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task.

Interaction between worsening cognitive function and deteriorating functional status on depressive symptoms among Chinese community-dwelling elders.

Aim: Cognitive impairment and functional deterioration are common in later life and often co-occur with depressive symptoms (DS). This study aims to examine the individual effects and possible interaction between worsening cognitive function (CF) and deteriorating functional status (FS) on DS using large sample, longitudinal data.

Methods: Elderly people who completed the baseline survey of China Health and Retirement Longitudinal Study (CHARLS 2011) and the third wave survey (2015) were included.

Chronic neck pain and depression: the mediating role of sleep quality and exercise.

Previous researches have found that chronic neck pain was closely related to depression. However, the relation between chronic neck pain, sleep quality, exercise and depression remains unclear. This study aims to evaluate the association between these factors, based on the assumption that sleep quality and exercise are potential mediators in the relationship between chronic neck pain and depression.

Attenuation of secondary damage and Aβ deposits in the ipsilateral thalamus of dMCAO rats through reduction of cathepsin B by bis(propyl)-cognitin, a multifunctional dimer.

Delayed secondary degeneration in the non-ischemic sites such as ipsilateral thalamus would occur after cortical infarction. Hence, alleviating secondary damage is considered to be a promising novel target for acute stroke therapy. In the current study, the neuroprotective effects of bis(propyl)-cognitin (B3C), a multifunctional dimer, against secondary damage in the VPN of ipsilateral thalamus were investigated in a distal middle cerebral artery occlusion (dMCAO) stroke model in adult rats.

Optimization of in silico tools for predicting genetic variants: individualizing for genes with molecular sub-regional stratification.

Genes are unique in functional role and differ in their sensitivities to genetic defects, but with difficulties in pathogenicity prediction. This study attempted to improve the performance of existing in silico algorithms and find a common solution based on individualization strategy. We initiated the individualization with the epilepsy-related SCN1A variants by sub-regional stratification.

Synaptic clustering differences due to different GABRB3 mutations cause variable epilepsy syndromes.

GABRB3 is highly expressed early in the developing brain, and its encoded β3 subunit is critical for GABAA receptor assembly and trafficking as well as stem cell differentiation in embryonic brain. To date, over 400 mutations or variants have been identified in GABRB3. Mutations in GABRB3 have been increasingly recognized as a major cause for severe paediatric epilepsy syndromes such as Lennox-Gastaut syndrome, Dravet syndrome and infantile spasms with intellectual disability as well as relatively mild epilepsy syndromes such as childhood absence epilepsy.

HLA-B13:01 as a Risk Allele for Antiepileptic Drugs-Induced Cutaneous Adverse Reactions: Higher Risk for Cross-Reactivity?

Antiepileptic drugs frequently cause cutaneous adverse reactions (cADRs). Numerous studies have reported associations between human leukocyte antigen (HLA) alleles and cADRs caused by single antiepileptic drug in Southern Han Chinese people. However, the relationship between the HLA allele and cADRs sequentially induced by two or more antiepileptic drugs (AEDs-induced cross-reactivity) is unclear.

SFKs/p38 Pathway is Involved in Radicular Pain by Promoting Spinal Expression of Pro-Inflammatory Cytokines in a Rat Model of Lumbar Disc Herniation.

Study Design: A controlled, randomized, animal study.

Objective: The aim of this study was to investigate the role of src-family kinases/p38 pathway in a rat model of lumbar disc herniation (LDH).

Summary Of Background Data: LDH always generates radicular pain, and the mechanism remains unclear.

A missense mutation in SLC6A1 associated with Lennox-Gastaut syndrome impairs GABA transporter 1 protein trafficking and function.

Background: Mutations in SLC6A1 have been associated mainly with myoclonic atonic epilepsy (MAE) and intellectual disability. We identified a novel missense mutation in a patient with Lennox-Gastaut syndrome (LGS) characterized by severe seizures and developmental delay.

Methods: Exome Sequencing was performed in an epilepsy patient cohort.

Hypoxic postconditioning activates the Wnt/β-catenin pathway and protects against transient global cerebral ischemia through Dkk1 Inhibition and GSK-3β inactivation.

The Wingless/Int (Wnt)/β-catenin pathway plays an essential role in cell survival. Although postconditioning with 8% oxygen can alleviate transient global cerebral ischemia (tGCI)-induced neuronal damage in hippocampal CA1 subregion in adult rats as demonstrated by our previous studies, little is understood about the role of Wnt/β-catenin pathway in hypoxic postconditioning (HPC)-induced neuroprotection. This study tried to investigate the involvement of Wnt/β-catenin pathway in HPC-induced neuroprotection against tGCI and explore the underlying molecular mechanism thereof.