Comparison of Culturing Methods of Primary Vaginal Fibroblasts.

Importance: Vaginal fibroblast function is altered in people with pelvic organ prolapse. Thus, it is important to study vaginal fibroblasts to better understand the pathophysiology of prolapse.

Objective: This study aimed to compare 3 culturing methods of primary vaginal fibroblasts.

Brain-targeting liposome-based gene delivery exacerbates soluble amyloid-β accumulation in mice.

Alzheimer's disease (AD) is the most common cause of late-life dementia characterized by progressive neurodegeneration and brain deposition of amyloid-β (Aβ) and phosphorylated tau. The ε2 encoding apolipoprotein E () is a protective allele against AD among the three genotypes ( ε2, ε3, ε4), while is the strongest genetic factor substantially increasing AD risk. APOE regulates brain lipid homeostasis and maintaining synaptic plasticity and neuronal function, where has a superior function compared to and .

Secretome from iPSC-derived MSCs exerts proangiogenic and immunosuppressive effects to alleviate radiation-induced vascular endothelial cell damage.

Background: Radiation therapy is the standard of care for central nervous system tumours. Despite the success of radiation therapy in reducing tumour mass, irradiation (IR)-induced vasculopathies and neuroinflammation contribute to late-delayed complications, neurodegeneration, and premature ageing in long-term cancer survivors. Mesenchymal stromal cells (MSCs) are adult stem cells that facilitate tissue integrity, homeostasis, and repair.

ABCA7 deficiency causes neuronal dysregulation by altering mitochondrial lipid metabolism.

ABCA7 loss-of-function variants are associated with increased risk of Alzheimer's disease (AD). Using ABCA7 knockout human iPSC models generated with CRISPR/Cas9, we investigated the impacts of ABCA7 deficiency on neuronal metabolism and function. Lipidomics revealed that mitochondria-related phospholipids, such as phosphatidylglycerol and cardiolipin were reduced in the ABCA7-deficient iPSC-derived cortical organoids.

A Mutant Methionyl-tRNA Synthetase-Based toolkit to assess induced-Mesenchymal Stromal Cell secretome in mixed-culture disease models.

Mesenchymal stromal cells (MSCs) have a dynamic secretome that plays a critical role in tissue repair and regeneration. However, studying the MSC secretome in mixed-culture disease models remains challenging. This study aimed to develop a mutant methionyl-tRNA synthetase-based toolkit (MetRS ) to selectively profile secreted proteins from MSCs in mixed-culture systems and demonstrate its potential for investigating MSC responses to pathological stimulation.

LRP1 in vascular mural cells modulates cerebrovascular integrity and function in the presence of APOE4.

Cerebrovasculature is critical in maintaining brain homeostasis; its dysregulation often leads to vascular cognitive impairment and dementia (VCID) during aging. VCID is the second most prevalent cause of dementia in the elderly, after Alzheimer's disease (AD), with frequent cooccurrence of VCID and AD. While multiple factors are involved in the pathogenesis of AD and VCID, APOE4 increases the risk for both diseases.

Loss of Tmem106b exacerbates FTLD pathologies and causes motor deficits in progranulin-deficient mice.

Progranulin (PGRN) and transmembrane protein 106B (TMEM106B) are important lysosomal proteins implicated in frontotemporal lobar degeneration (FTLD) and other neurodegenerative disorders. Loss-of-function mutations in progranulin (GRN) are a common cause of FTLD, while TMEM106B variants have been shown to act as disease modifiers in FTLD. Overexpression of TMEM106B leads to lysosomal dysfunction, while loss of Tmem106b ameliorates lysosomal and FTLD-related pathologies in young Grn mice, suggesting that lowering TMEM106B might be an attractive strategy for therapeutic treatment of FTLD-GRN.

Loss of TMEM106B leads to myelination deficits: implications for frontotemporal dementia treatment strategies.

Genetic variants that define two distinct haplotypes at the TMEM106B locus have been implicated in multiple neurodegenerative diseases and in healthy brain ageing. In frontotemporal dementia (FTD), the high expressing TMEM106B risk haplotype was shown to increase susceptibility for FTD with TDP-43 inclusions (FTD-TDP) and to modify disease penetrance in progranulin mutation carriers (FTD-GRN). To elucidate the biological function of TMEM106B and determine whether lowering TMEM106B may be a viable therapeutic strategy, we performed brain transcriptomic analyses in 8-month-old animals from our recently developed Tmem106b-/- mouse model.

Loss of Tmem106b is unable to ameliorate frontotemporal dementia-like phenotypes in an AAV mouse model of C9ORF72-repeat induced toxicity.

Loss-of-function mutations in progranulin (GRN) and a non-coding (GGGGCC) hexanucleotide repeat expansions in C9ORF72 are the two most common genetic causes of frontotemporal lobar degeneration with aggregates of TAR DNA binding protein 43 (FTLD-TDP). TMEM106B encodes a type II transmembrane protein with unknown function. Genetic variants in TMEM106B associated with reduced TMEM106B levels have been identified as disease modifiers in individuals with GRN mutations and C9ORF72 expansions.