HαT prevalence is increased in both clonal and non-clonal mast cell-associated disorders where it augments symptoms of immediate hypersensitivity, including anaphylaxis. The unique properties of naturally occurring α/β-tryptase heterotetramers may explain certain elements of phenotypes associated with HαT, though additional mechanisms are being evaluated. This review provides an overview of the clinical and translational studies that have identified HαT as a modifier of mast cell-associated disorders and anaphylaxis and discusses mechanisms that may potentially explain some of these clinical findings.
  To present a method enabling in vivo quantification of tissue membrane potential (ΔΨ
  ), a proxy of mitochondrial membrane potential (ΔΨ
  ), to review the origin and role of ΔΨ
  , and to highlight potential applications of myocardial ΔΨ
  imaging.
 
  Radiolabelled lipophilic cations have been used for decades to measure ΔΨ
  in vitro. Using similar compounds labeled with positron emitters and appropriate compartment modeling, this technique now allows in vivo quantification of ΔΨ
  with positron emission tomography. Studies have confirmed the feasibility of measuring myocardial ΔΨ
  in both animals and humans. In addition, ΔΨ
  showed very low variability among healthy subjects, suggesting that this method could allow detection of relatively small pathological changes. In vivo assessment of myocardial ΔΨ
  provides a new tool to study the pathophysiology of cardiovascular diseases and has the potential to serve as a new biomarker to assess disease stage, prognosis, and response to therapy.
 Radiolabelled lipophilic cations have been used for decades to measure ΔΨm in vitro. Using similar compounds labeled with positron emitters and appropriate compartment modeling, this technique now allows in vivo quantification of ΔΨT with positron emission tomography. Studies have confirmed the feasibility of measuring myocardial ΔΨT in both animals and humans. In addition, ΔΨT showed very low variability among healthy subjects, suggesting that this method could allow detection of relatively small pathological changes. In vivo assessment of myocardial ΔΨT provides a new tool to study the pathophysiology of cardiovascular diseases and has the potential to serve as a new biomarker to assess disease stage, prognosis, and response to therapy.
  Although opioids are excellent analgesics, they are associated with severe short- and long-term side effects that are especially concerning for the treatment of chronic pain. Peripherally acting opioid receptor agonists promise to mitigate the more serious centrally mediated side effects of opioids, and the goal of this paper is to identify and elaborate on recent advances in these peripheral opioid receptor therapeutics.
 
  Peripheral opioid receptor agonists are effective analgesics that at the same time circumvent the problem of centrally mediated opioid side effects by (1) preferentially targeting peripheral opioid receptors that are often the source of the pain and (2) their markedly diminished permeability or activity across the blood-brain barrier. Recent novel bottom-up approaches have been notable for the design of therapeutics that are either active only at inflamed tissue, as in the case of fentanyl-derived pH-sensitive opioid ligands, or too bulky or hydrophilic to cross the blood-brain barrier, her active only at inflamed tissue, as in the case of fentanyl-derived pH-sensitive opioid ligands, or too bulky or hydrophilic to cross the blood-brain barrier, as in the case of morphine covalently bound to hyperbranched polyglycerols. Recent innovations in peripheral opioid receptor therapeutics of pH-sensitive opioid ligands and limiting opioid permeability across the blood-brain barrier have had promising results in animal models. While this is grounds for optimism that some of these therapeutics will be efficacious in human subjects at a future date, each drug must undergo individualized testing for specific chronic pain syndromes to establish not only the nuances of each drug's therapeutic effect but also a comprehensive safety profile.
  Non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and circular RNAs (circRNAs) are pivotal regulators of mRNA and protein expression that critically contribute to cardiovascular pathophysiology. Although little is known about the origin and function of such ncRNAs, they have been suggested as promising biomarkers with powerful therapeutic value in cardiovascular disease (CVD). In this review, we summarize the most recent findings on ncRNAs biology and their implication on cholesterol homeostasis and lipoprotein metabolism that highlight novel therapeutic avenues for treating dyslipidemia and atherosclerosis.
 
  Clinical and experimental studies have elucidated the underlying effects that specific miRNAs impose both directly and indirectly regulating circulating high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) metabolism and cardiovascular risk. Some of these relevant miRNAs include miR-148a, miR-128-1, miR-483, miR-520d, miR-224, miR-30c, miR-122, miRin (LDL), and very low-density lipoprotein (VLDL) metabolism and cardiovascular risk. Some of these relevant miRNAs include miR-148a, miR-128-1, miR-483, miR-520d, miR-224, miR-30c, miR-122, miR-33, miR-144, and miR-34. circRNAs are known to participate in a variety of physiological and pathological processes due to their abundance in tissues and their stage-specific expression activation. Recent studies have proven that circRNAs may be considered targets of CVD as well. Some of these cirRNAs are circ-0092317, circ_0003546, circ_0028198, and cirFASN that have been suggested to be strongly involved in lipoprotein metabolism; however, their relevance in CVD is still unknown.  https://www.selleckchem.com/products/lurbinectedin.html  MicroRNA and cirRNAs have been proposed as powerful therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field of lipid and lipoprotein metabolism underscoring the novel mechanisms by which some of these ncRNAs influence lipoprotein metabolism and CVD.