The Apoptotic Effects of Methylparaben and Ultraviolet B Light on M624 Human Melanoma Cells

Methylparaben is a commonly used antimicrobial in cosmetics that has been shown to have negative effects on mammalian cells. Human melanoma M624 cells were treated with 1 and 5 mM methylparaben in the presence and absence of 25 mJ/cm2 ultraviolet B (UV-B) light. Cell proliferation assays showed that 5 mM methylparaben was toxic to M624 cells after 24 hours. Apoptotic signaling pathways were analyzed via isolation of separate cellular compartments and protein analysis via western blot. Upon 5 mM methylparaben treatment, PARP I was cleaved indicating apoptosis, which was mediated by the TNF-α receptor activated in the lipid rafts of the M624 cells. Upon 25 mJ/cm2 UV-B radiation, PARP II was activated indicating cellular damage, cytochrome c was released from the mitochondria, and caspase-3 was expressed. Upon combinatory treatment with 5 mM methylparaben and 25 mJ/cm2 UV-B, apoptosis was induced through mitochondrial release of cytochrome c, expression of caspase-3 and cleavage of PARP I, while methylparaben-induced TNF-α receptor activation and UV-B-induced PARP II activation was inhibited., demonstrating that antimicrobial methylparaben in cosmetics can cause damage to cells

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder

A Multi-disciplinary Commentary on Preclinical Research to investigate Vascular Contributions to Dementia

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis. This review by a multidisciplinary, diverse (in terms of sex, geography and career stage), cross-institute team provides a perspective on limitations to current VCI models and recommendations for improving translation and reproducibility. We discuss reproducibility, clinical features of VCI and corresponding assessments in models, human pathology, bioinformatics approaches, and data sharing. We offer recommendations for future research, particularly focusing on small vessel disease as a main underpinning disorder.</p