Methylene Blue (MB), following its introduction to biology in the 19 th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system.
Abnormal protein aggregation in the brain is linked to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Recent studies revealed that the oligomeric form of aggregates is most likely the toxic species, and thus could be a good therapeutic target. To screen for potent inhibitors that can inhibit both oligomerisation and fibrillation of α-synuclein (α-syn), we systematically compared the antioligomeric and antifibrillar activities of eight compounds that were extracted from Chinese herbal medicines through three platforms that can monitor the formation of α-syn fibrils and oligomers in cell-free or cellular systems. Our results revealed that baicalein, a flavonoid extracted from the Chinese herbal medicine Scutellaria baicalensis Georgi ("huang qin" in Chinese), is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-syn fibrillation in cell-free systems. We further tested the protective effect of baicalein against α-syn-oligomer-induced toxicity in neuronal cells. Our data showed that baicalein inhibited the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protected SH-SY5Y cells from α-syn-oligomer-induced toxicity. We also explored the effect of baicalein on amyloid-β peptide (Aβ) aggregation and toxicity. We found that baicalein can also inhibit Aβ fibrillation and oligomerisation, disaggregate pre-formed Aβ amyloid fibrils and prevent Aβ fibril-induced toxicity in PC12 cells. Our study indicates that baicalein is a good inhibitor of amyloid protein aggregation and toxicity. Given the role of these processes in neurodegenerative diseases such as AD and PD, our results suggest that baicalein has potential as a therapeutic agent for the treatment of these devastating disorders.
Background: Comprehensive global data on the health effects of indoor air pollutants are lacking. There are few large population-based multi–air pollutant health assessments. Further, little is known about indoor air health risks in the Middle East, especially in countries undergoing rapid economic development.Objectives: To provide multifactorial indoor air exposure and health data, we conducted a population-based study of indoor air pollution and health in the United Arab Emirates (UAE).Methods: We conducted a cross-sectional study in a population-based sample of 628 households in the UAE. Indoor air pollutants [sulfur dioxide (SO2), nitrogen dioxide (NO2), hydrogen sulfide (H2S), formaldehyde (HCHO), carbon monoxide (CO), and particulate matter] were measured using passive samplers over a 7-day period. Health information was collected from 1,590 household members via in-person interviews.Results: Participants in households with quantified SO2, NO2, and H2S (i.e., with measured concentrations above the limit of quantification) were twice as likely to report doctor-diagnosed asthma. Participants in homes with quantified SO2 were more likely to report wheezing symptoms {ever wheezing, prevalence odds ratio [POR] 1.79 [95% confidence interval (CI) 1.05, 3.05]; speech-limiting wheeze, POR 3.53 (95% CI: 1.06, 11.74)}. NO2 and H2S were similarly associated with wheezing symptoms. Quantified HCHO was associated with neurologic symptoms (difficulty concentrating POR 1.47; 95% CI: 1.02, 2.13). Burning incense daily was associated with increased headaches (POR 1.87; 95% CI: 1.09, 3.21), difficulty concentrating (POR 3.08; 95% CI: 1.70, 5.58), and forgetfulness (POR 2.68: 95% CI: 1.47, 4.89).Conclusions: This study provides new information regarding potential health risks from pollutants commonly found in indoor environments in the UAE and other countries. Multipollutant exposure and health assessments in cohort studies are needed to better characterize health effects of indoor air pollutants.
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