Alcohol is one of the most commonly abused substances in the United States. Chronic consumption of ethanol has been responsible for numerous chronic diseases and conditions globally. The underlying mechanism of liver injury has been studied in depth, however, far fewer studies have examined other organs especially the heart and the central nervous system (CNS). The authors conducted a narrative review on the relationship of alcohol with heart disease and dementia. With that in mind, a complex relationship between inflammation and cardiovascular disease and dementia has been long proposed but inflammatory biomarkers have gained more attention lately. In this review we examine some of the consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver. The article reviews the potential role of inflammatory markers such as TNF-α in predicting dementia and/or cardiovascular disease. It was found that TNF-α could promote and accelerate local inflammation and damage through autocrine/paracrine mechanisms. Unraveling the mechanisms linking chronic alcohol consumption with proinflammatory cytokine production and subsequent inflammatory signaling pathways activation in the heart and CNS, is essential to improve our understanding of the disease and hopefully facilitate the development of new remedies.
Type IV pili (T4P) are retractable multifunctional nanofibers present on the surface of numerous bacterial and archaeal species. Their importance to microbiology is difficult to overstate.
Type IV pili (T4Ps) are a family of surface appendages that are important for adhesion, colonization, biofilm formation, virulence, twitching motility and many other functions. BfpU is an essential periplasmic protein of the T4P of Enteropathogenic Escherichia coli. Previous crosslinking and localization studies have shown that BfpU might interact with the outer membrane secretin BfpB, which is also essential for T4P biogenesis. To date, BfpU has no known homologs and its function is unknown. To purify BfpU, we performed affinity and size exclusion chromatography. Preliminary characterization of BfpU via thermal stability assay and circular dichroism suggests a melting temperature of 80 °C, and its secondary structure is comprised of ~40% anti‐parallel β‐sheet and ~45% random coil. The secondary structure profile is reminiscent of PilP, an essential periplasmic protein anchored in the membrane that interacts with secretins in other T4P systems. Additionally, random mutagenesis is in progress to assess essential residues of BfpU that may be involved in protein interactions within this T4P system. Single residue mutations from this mutagenesis screening will be used to confirm interaction sites within BfpU. The results of these studies will help clarify the role of BfpU in T4P biogenesis and its interactions with BfpB.
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