Adv Exp Med Biol
-
Mitochondria individually encapsulate their own genome, unlike other cellular organelles. Mitochondrial DNA (mtDNA) is a circular, double-stranded, 16,569-base paired DNA containing 37 genes: 13 proteins of the mitochondrial respiratory chain, two ribosomal RNAs (rRNAs; 12S and 16S), and 22 transfer RNAs (tRNAs). The mtDNA is more vulnerable to oxidative modifications compared to nuclear DNA because of its proximity to ROS-producing sites, limited presence of DNA damage repair systems, and continuous replication in the cell. mtDNA mutations can be inherited or sporadic. ⋯ In this chapter, we summarize our current understanding of mtDNA mutations and their role in cardiac involvement. In addition, epigenetic modifications of mtDNA are briefly discussed for future elucidation of their critical role in cardiac involvement. Finally, current strategies for dealing with mitochondrial mutations in cardiac disorders are briefly stated.
-
Historically, hemoglobin-based oxygen carriers (HBOCs) were being developed as "blood substitutes," despite their transient circulatory half-life (~ 24 h) vs. transfused red blood cells (RBCs). More recently, HBOC commercial development focused on "oxygen therapeutic" indications to provide a temporary oxygenation bridge until medical or surgical interventions (including RBC transfusion, if required) can be initiated. This included the early trauma trials with HemAssist ® (BAXTER), Hemopure ® (BIOPURE) and PolyHeme ® (NORTHFIELD) for resuscitating hypotensive shock. ⋯ This was key to the successful conduct of their Phase 2 program (ex-US, from 2009 to 2012) to evaluate MP4OX as an adjunct to standard fluid resuscitation and transfusion of RBCs. In 2013, SANGART shared their Phase 2b results with the FDA, and succeeded in getting the FDA to agree that a planned Phase 2c higher dose comparison study of MP4OX in trauma could include clinical sites in the US. Unfortunately, SANGART failed to secure new funding and was forced to terminate development and operations in Dec 2013, even though a regulatory path forward with FDA approval to proceed in trauma had been achieved.
-
Review
The Mechanistic Role of the Calcium-Activated Chloride Channel ANO1 in Tumor Growth and Signaling.
Multiple studies have described the high expression and amplification of Anoctamin 1 (ANO1) in various cancers, including, but not limited to breast cancer, head and neck cancer, gastrointestinal stromal tumors and glioblastoma. ANO1 has been demonstrated to be critical for tumor growth in breast and head and neck cancers through its regulation of EGFR signaling and pathway modulators like MAPK and protein kinase B. However, the discovery of ANO1 as a calcium activated chloride channel came as a surprise to the field and has given rise to many questions. How does a chloride channel promote oncogenesis? Is the chloride channel function of ANO1 important for its role in cancer? Does ANO1 exhibits chloride-independent functions in cancer cells? This review summarizes the current understanding of ANO1's function in cancer, provides a synopsis of the findings addressing the open questions in the field and gives an outlook on the promising future of ANO1 as a potential therapeutic target for the treatment of various cancers.
-
The oral microbiota represents an important part of the human microbiota, and includes several hundred to several thousand diverse species. It is a normal part of the oral cavity and has an important function to protect against colonization of extrinsic bacteria which could affect systemic health. On the other hand, the most common oral diseases caries, gingivitis and periodontitis are based on microorganisms. ⋯ On any non-shedding surfaces of the oral cavity dental plaque starts to form, which meets all criteria for a microbial biofilm and is subject to the so-called succession. When the sensitive ecosystem turns out of balance - either by overload or weak immune system - it becomes a challenge for local or systemic health. Therefore, the most common strategy and the golden standard for the prevention of caries, gingivitis and periodontitis is the mechanical removal of this biofilms from teeth, restorations or dental prosthesis by regular toothbrushing.
-
Since mass spectrometry was introduced as the core technology for large-scale analysis of the proteome, the speed of data acquisition, dynamic ranges of measurements, and data quality are continuously improving. These improvements are triggered by regular launches of new methodologies and instruments.