Our previous studies showed that protein kinase Cepsilon (PKCepsilon) verexpression in mouse skin resulted in metastatic squamous cell carcinoma (SCC) elicited by single 7,12-dimethylbenz(a)anthracene (DMBA)-initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promotion in the absence of preceding papilloma formation as is typically observed in wild type mice. The present study demonstrates that double-DMBA initiation modulates tumor incidence, multiplicity, and latency period in both wild type and PKCepsilon overexpression transgenic (PKCepsilon-Tg) mice. After 17 weeks (wks) of tumor promotion, a reduction in papilloma multiplicity was observed in double- versus single-DMBA initiated wild type mice. Papilloma multiplicity was inversely correlated with cell death indices of interfollicular keratinocytes, indicating decreased papilloma formation was caused by increased cell death and suggesting the origin of papillomas is in interfollicular epidermis. Double-initiated PKCepsilon-Tg mice had accelerated carcinoma formation and cancer incidence in comparison to single-initiated PKCepsilon-Tg mice. Morphologic analysis of mouse skin following double initiation and tumor promotion showed a similar if not identical series of events to those previously observed following single initiation and tumor promotion: putative preneoplastic cells were observed arising from hyperplastic hair follicles (HFs) with subsequent cancer cell infiltration into the dermis. Single-initiated PKCepsilon-Tg mice exhibited increased mitosis in epidermal cells of HFs during tumor promotion.
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http://dx.doi.org/10.1080/01926230701748164 | DOI Listing |
Alzheimers Dement
December 2024
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A., Philadelphia, PA, USA.
Background: The vicious cycle between depression and dementia increases the risk of Alzheimer's Disease (AD) pathogenesis and pathology. This study investigates therapeutic effectiveness versus side effects and the underlying mechanisms of intranasal dantrolene nanoparticles (IDNs) to treat depression behavior and memory loss in 5XFAD mice.
Method: 5XFAD and wild-type B6SJLF1/J mice were treated with IDNs (IDN, 5 mg/kg) in Ryanodex formulation for a duration of 12 weeks.
Background: Focused ultrasound (FUS)-induced blood-brain barrier opening (BBBO) is a technique for safely, non-invasively, and transiently opening the blood brain barrier in a targeted area of the brain. Pre-clinical and clinical studies have shown that FUS is capable of decreasing amyloid plaque load and stimulating neurogenesis in Alzheimer's Disease (AD) models, in addition to being safe for use in human patients. However, the effect of FUS-BBBO on neurons has not yet been characterized, despite its crucial role in cognition and regulating brain function.
View Article and Find Full Text PDFBackground: Impaired Aβ clearance plays a key role in the common, late-onset AD. Anti-Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG-PE3 crossing the human blood-brain barrier (BBB) and clearing Aβ with no adverse effect.
View Article and Find Full Text PDFBackground: Convergent evidence indicates that deficits in the endosomal recycling pathway underlies pathogenesis of Alzheimer's disease (AD). SORL1 encodes the retromer-associated receptor SORLA that plays an essential role in recycling of AD-associated cargos such as the amyloid precursor protein and the glutamatergic AMPA receptor. Importantly, loss of function pathogenic SORL1 variants are associated with AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Université de Lille, Lille, Hauts-de-France, France.
Background: Tau proteins aggregate in a number of neurodegenerative disorders known as tauopathies. Various studies have highlighted the role of microtubule-binding domains in the intracellular aggregation of Tau protein.
Method: Using a library of synthetic VHHs humanized in collaboration with Hybrigenics, we have developed a number of anti-tau VHHs.
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