Synaptojanin 1 Modulates Functional Recovery After Incomplete Spinal Cord Injury in Male Apolipoprotein E Epsilon 4 Mice.

Apolipoprotein E epsilon 4 (ApoE4) is the second most common variant of ApoE, being present in ∼14% of the population. Clinical reports identify ApoE4 as a genetic risk factor for poor outcomes after traumatic spinal cord injury (SCI) and spinal cord diseases such as cervical myelopathy. To date, there is no intervention to promote recovery of function after SCI/spinal cord diseases that is specifically targeted at ApoE4-associated impairment.

Sex specific molecular networks and key drivers of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive and age-associated neurodegenerative disorder that affects women disproportionally. However, the underlying mechanisms are poorly characterized. Moreover, while the interplay between sex and ApoE genotype in AD has been investigated, multi-omics studies to understand this interaction are limited.

Molecular differences in brain regional vulnerability to aging between males and females.

Background: Aging-related cognitive decline is associated with brain structural changes and synaptic loss. However, the molecular mechanisms of cognitive decline during normal aging remain elusive.

Results: Using the GTEx transcriptomic data from 13 brain regions, we identified aging-associated molecular alterations and cell-type compositions in males and females.

Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer's Disease.

To identify the molecular mechanisms and novel therapeutic targets of late-onset Alzheimer's Disease (LOAD), we performed an integrative network analysis of multi-omics profiling of four cortical areas across 364 donors with varying cognitive and neuropathological phenotypes. Our analyses revealed thousands of molecular changes and uncovered neuronal gene subnetworks as the most dysregulated in LOAD. ATP6V1A was identified as a key regulator of a top-ranked neuronal subnetwork, and its role in disease-related processes was evaluated through CRISPR-based manipulation in human induced pluripotent stem cell-derived neurons and RNAi-based knockdown in Drosophila models.

MicroRNA-195 rescues ApoE4-induced cognitive deficits and lysosomal defects in Alzheimer's disease pathogenesis.

Our recent findings link the apolipoprotein E4 (ApoE4)-specific changes in brain phosphoinositol biphosphate (PIP) homeostasis to the susceptibility of developing Alzheimer's Disease (AD). In the present study, we have identified miR-195 as a top micro-RNA candidate involved in the ApoE/PIP pathway using miRNA profiles in human ROSMAP datasets and mouse microarray studies. Further validation studies have demonstrated that levels of miR-195 are significantly lower in human brain tissue of ApoE4 patients with clinical diagnosis of mild cognitive impairment (MCI) or early AD when compared to ApoE4 subjects.

Sex differences in Alzheimer's disease: Understanding the molecular impact.

Alzheimer's disease (AD) is a common neurodegenerative disorder that presents with cognitive impairment and behavioral disturbance. Approximately 5.5 million people in the United States live with AD, most of whom are over the age of 65 with two-thirds being woman.

ApoE4-associated phospholipid dysregulation contributes to development of Tau hyper-phosphorylation after traumatic brain injury.

The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP degrading enzyme, synaptojanin 1 (synj1).

Abnormal Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Partially Mimicked Development of TSC2 Neurological Abnormalities.

Tuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.

Adipose-derived stem cells enhance myogenic differentiation in the mdx mouse model of muscular dystrophy paracrine signaling.

Adipose-derived stem cells have been shown to promote peripheral nerve regeneration through the paracrine secretion of neurotrophic factors. However, it is unclear whether these cells can promote myogenic differentiation in muscular dystrophy. Adipose-derived stem cells (6 × 10) were injected into the gastrocnemius muscle of mdx mice at various sites.

BMP4 inhibits myogenic differentiation of bone marrow-derived mesenchymal stromal cells in mdx mice.

Background Aims: Bone marrow-derived mesenchymal stromal cells (BMSCs) are a promising therapeutic option for treating Duchenne muscular dystrophy (DMD). Myogenic differentiation occurs in the skeletal muscle of the mdx mouse (a mouse model of DMD) after BMSC transplantation. The transcription factor bone morphogenic protein 4 (BMP4) plays a crucial role in growth regulation, differentiation and survival of many cell types, including BMSCs.

[Analysis of phenotype and genotype in a family with late infantile metachromatic leukodystrophy].

Objective: To study genotype-phenotype correlation of a family with late infantile metachromatic leukodystrophy(MLD).

Methods: Clinical data were collected and ARSA gene was tested by PCR and sequencing in a pedigree.

Results: The male proband onset with walking dysfunction at 19 months, arylsulfatase A activity of leucocyte from his peripheral blood was 20.

[Study on Duchenne muscular dystrophy gene mutation and prenatal diagnosis].

Objective: To explore the characteristics of DNA mutations underlying Duchenne muscular dystrophy and provide prenatal diagnosis.

Methods: Multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) were applied for analyzing DMD gene mutations in 388 unrelated Chinese patients and 53 fetuses.

Results: Respectively, 230 and 43 subjects were found to harbor a deletion (59.

[Correlation between genotypes and phenotypes in pseudohypertrophic muscular dystrophy].

Objective: To explore the correlation between genotypes and phenotypes in Chinese patients with pseudohypertrophic muscular dystrophy.

Methods: Patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) were diagnosed clinically. Multiplex ligation-dependent probe amplification (MLPA) were performed to detect potential DMD gene mutations.

Decorin promotes myogenic differentiation and mdx mice therapeutic effects after transplantation of rat adipose-derived stem cells.

Background Aims: Adipose-derived stem cells (ADSC) have been considered as attractive candidates for the treatment of Duchenne muscular dystrophy (DMD), but the rate of ADSC myogenesis is very low. Myostatin (Mstn), a negative regulator of myogenesis, is known to be responsible for limiting skeletal muscle regeneration. Decorin could bind Mstn and deactivate it.

[Genotypic and clinical features of spinal muscular atrophy type 3].

Objective: To explore the genotypic and clinical features and laboratory examinations of spinal muscular atrophy type 3 (SMA III).

Methods: Results of genetic testing and laboratory exams of 18 SMA III patients were collected and analyzed.

Results: The average age of onset of patients was 6.

Restoration of muscle fibers and satellite cells after isogenic MSC transplantation with microdystrophin gene delivery.

Duchenne muscular dystrophy is the most prevalent inheritable muscle disease. Transplantation of autologous stem cells with gene direction is an ideal therapeutic approach for the disease. The current study aimed to investigate the restoration of myofibers in mdx mice after mdx bone marrow-derived mesenchymal stem cell (mMSC) transplantation with human microdystrophin delivery.

Comparative study of myocytes from normal and mdx mice iPS cells.

Recently, induced pluripotent stem cells (iPS cells) have been derived from various techniques and show great potential for therapy of human diseases. Furthermore, the iPS technique can be used to provide cell models to explore pathological mechanisms of many human diseases in vitro, such as Duchenne muscular dystrophy (DMD), which is a severe recessive X-linked form of muscular dystrophy without effective treatment. In this study, we try to determine whether there are different characteristics of myocytes from mdx iPS cells and C57BL/10 iPS cells.

[Clinical, familial and hereditary analysis of myotonic dystrophy].

Objective: To analyze the clinical, familial and hereditary features of myotonic dystrophy to improve the knowledge and provide molecule evidence for gene diagnosis and prenatal diagnosis of myotonic dystrophy or dystrophia myotonia (DM) families.

Methods: Clinical data of 2 DM families were collected based on the probands. The number of trinucleotide CTG repeat in the 3' untranslated region of myotonic dystrophy protein kinase (DMPK) gene on chromosome 19 was determined by DNA sequence and repeat fragment.

[Study of dystrophin gene non-deletion/duplication mutations causing Becker muscular dystrophy].

Objective: To identify potential mutations in patients featuring Becker muscular dystrophy (BMD) and to enhance the understanding of non-deletion/duplication mutations of the dystrophin gene causing BMD.

Methods: Clinical data of two patients affected with BMD were collected. Potential mutations in the dystrophin gene were screened with multiplex ligation-dependent probe amplification assay (MLPA).

Directed differentiation of motor neuron cell-like cells from human adipose-derived stem cells in vitro.

The capacity of human adipose-derived stem cells (hADSCs) to differentiate into motor neurons and the identity of molecular factors that confer hADSCs with the competence of motor neurons have yet to be elucidated. Here, retinoic acid and sonic hedgehog were applied to examine whether hADSCs could be differentiated into motor neurons. As early as 6 h after induction, hADSCs were changed toward neuronal morphology.