Discrete and punctate nuclear RNA foci are characteristic molecular hallmarks of pathogenesis in myotonic dystrophy type 1 and type 2. Intranuclear RNA inclusions of distinct morphology have also been found in fragile X-associated tremor ataxia syndrome, Huntington's disease-like 2, spinocerebellar ataxias type 8, type 10 and type 31. These neurological diseases are associated with the presence...

Amyloid oligomers have emerged as the most toxic species of amyloid-β (Aβ). This hypothesis might explain the lack of correlation between amyloid plaques and memory impairment or cellular dysfunction. However, despite the numerous published research articles supporting the critical role Aβ oligomers in synaptic dysfunction and cell death, the exact definition and mechanism of amyloid oligomers ...

The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interferin...

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality....

Inclusions of TAR DNA-binding protein-43 (TDP-43), a nuclear protein that regulates transcription and RNA splicing, are the defining histopathological feature of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-Us) and sporadic and familial forms of amyotrophic lateral sclerosis (ALS). In ALS and FTLD-U, aggregated, ubiquitinated, and N-terminally truncated TDP-43 can ...

Lead is a toxic heavy metal that can cause a range of health problems. In this context, the vascular system is a particular target of the deleterious effects of lead. Lead exerts its toxicity through substitution of other divalent cations such as calcium and zinc, resulting in disruption of homeostasis. Based on the evidence that lead up-regulates endoplasmic reticulum (ER) chaperone glucose-re...

Chronic inflammation results in increased nitrogen monoxide (.NO) formation and the accumulation of nitrite (NO(2-)). Neutrophils stimulated by various inflammatory mediators release myeloperoxidase to produce the cytotoxic agent hypochlorous acid (HOCl). Exposure of chondrocytic SW1353 cells to HOCl resulted in a concentration- and time-dependent loss in viability, ATP, and glutathione levels....

OBJECTIVE This study aimed to evaluate the cellular toxicity of two newly-released acrylic resins (Futura Gen and GC Reline Hard) in comparison with the conventional heat-cure resin (Meliodent). MATERIALS AND METHODS Sample discs from each acrylic resin were placed in 24-well culture plates along with L929 mouse fibroblast cell line. A mixture of the RPMI 1640 medium, antibiotics and 10% FBS ...

Soldiers are exposed to multiple stress conditions adverse psychological, physico-chemical and environmental conditions during warfare which can result in significant physical and chemical alterations in the biological system. The effects of carbamate (pyridostigmine bromide, PB) pretreatment prior to physiological stress and organophosphorous compound, DFP (diisopropylfluorophosphate) exposure...

Intracerebral deposition of unconjugated bilirubin is believed to be primarily responsible for the neurological manifestations of kernicterus1 (1). Numerous in vitro studies have been carried out on the effect of unconjugated bilirubin on metabolic activity of liver and brain mitochondria (2), brain homogenates (3), cells grown in tissue culture (4, 5), and unicellular organisms (6). The majori...