Objective: To investigate the effects of finasteride on capillary in the ventral prostate of rat and study the mechanisms therein involved,
Methods: Male SD rats were given via gavage finasteride 40 mg/kg per day for 7 days (group B) and for 14 days (group C). The changes of capillary infused with Chinese ink were observed with the use of HE staining. Immunohistochemical (IHC) SP-method was adopted in measuring the protein expression of VEGF and eNOS in rat prostatic tissue.
Results: In comparison with the relevant values measured in the control group (group A), the microvessel density (MVD) values in group B and group C decreased by 35.2% and 56% respectively, the protein expression of VEGF in group B and group C decreased by 31.7% and 62.6% respectively, the protein expression of eNOS in group B and group C decreased by 15.7% and 52.5% respectively.
Conclusion: Finasteride can inhibit the protein expression of VEGF and eNOS and thereby can suppress angiogenesis of capillary in the ventral prostate of rat.
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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: There is an urgent need for new therapeutic and diagnostic targets for Alzheimer's disease (AD). Dementia afflicts roughly 55 million individuals worldwide, and the prevalence is increasing with longer lifespans and the absence of preventive therapies. Given the demonstrated heterogeneity of Alzheimer's disease in biological and genetic components, it is critical to identify new therapeutic approaches.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.
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
MRC Protein Phosphorylation and Ubiquitylation Unit, Dundee, Scotland, United Kingdom.
Background: Accumulation of misfolded a-synuclein protein in intracellular inclusion bodies of dopaminergic neurons underlies the pathogenesis of synucleinopathies, which include Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). Therefore, clearance of misfolded α-synuclein from dopaminergic neurons could in principle offer a an approach for modifying synucleinopathies, which currently remain untreatable.
Method: In this study, we employ the Affinity-directed PROtein Missile (AdPROM) system consisting of the substrate receptor of the CUL2-E3 ligase complex VHL and a nanobody selectively recognising the human α-synuclein protein RESULT: We demonstrate targeted degradation of endogenous α-synuclein from human cell lines with exquisite selectivity.
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