Translational research : the journal of laboratory and clinical medicine
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Over the past 25 years, naloxone has emerged as a critical lifesaving overdose antidote. Public health advocates and community activists established early methods for naloxone distribution to people who inject drugs, but a legacy of stigmatization and opposition to universal naloxone access continues to limit the drug's full potential to reduce opioid-related mortality. The establishment of naloxone distribution programs under the umbrella of syringe exchange programs faces the same practical, ideological and financial barriers to expansion similar to those faced by syringe exchange programs themselves. ⋯ Considerable naloxone "deserts" remain and even where there is naloxone access, it does not always reach those at risk. Promising areas for expansion include the development of more robust telehealth methods for naloxone distribution, including subsidized mail delivery programs; lowering barriers to pharmacy access; working with hospitals, ambulances, and law enforcement to expand naloxone "leave behind" programs; providing naloxone co-prescription with medications for opioid use disorder; and working with prisons, shelters, and networks of people who use drugs to increase access to the lifesaving medication. Efforts to ensure over-the-counter and low- or no-cost naloxone are ongoing and stand alongside medication-assisted treatments as efficacious, readily-actionable, and cost-efficient population-level interventions available for combatting opioid-related overdose in the United States.
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Once thought of as arising from "junk DNA," noncoding RNAs (ncRNAs) have emerged as key molecules in cellular processes and response to stress. From diseases such as cancer, coronary artery disease, and diabetes to the effects of ionizing radiation (IR), ncRNAs play important roles in disease progression and as biomarkers of damage. Noncoding RNAs regulate cellular processes by competitively binding DNA, mRNA, proteins, and other ncRNAs. ⋯ Furthermore, some studies have reported modulation of radiosensitivity by altering expression levels of these ncRNAs. This review discusses the roles of ncRNAs in the radiation response and evaluates prior research on ncRNAs as biomarkers of radiation damage. Future directions and applications of ncRNAs in radiation research are introduced, including the potential for a clinical ncRNA assay for assessing radiation damage and for the therapeutic use of RNA interference (RNAi).
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The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). ⋯ The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an antiapoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence.
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Clinical observation and ex vivo studies have established a strong association between inflammation and postoperative atrial fibrillation (POAF). However, it is unclear whether the inflammatory phenotype is causally linked to this event or is an epiphenomenon, and it is not known which inflammatory meditators may increase susceptibility to POAF. The limitations of available animal models of spontaneous POAF (sPOAF) makes it difficult to select an experimental system. Here, we provide experimental and clinical evidence for mechanistic involvement of interleukin-6 (IL-6) in sPOAF.
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Activation of the innate immune system represents a vital step in inflammation during cardiac remodeling induced by the angiotensin II (Ang II). This study aimed to explore the role of Toll-like receptors 2 (TLR2) in Ang II-induced cardiac remodeling. We investigated the effect of TLR2 deficiency on Ang II-induced cardiac remodeling by utilizing TLR2 knockout mice, bone marrow transplantation models, and H9C2 cells. ⋯ Moreover, Ang II significantly increased TLR2-MyD88 interaction in H9C2 cells in a TLR4-independent manner. TLR2 deficiency in cardiac cells prevents Ang II-induced cardiac remodeling, inflammation and dysfunction through reducing the formation of TLR2-MyD88 complexes. Inhibition of TLR2 pathway may be a therapeutic strategy of hypertensive heart failure.