Dataset Information

Human Sirtuin Regulators: The "Success" Stories.

ABSTRACT: The human sirtuins are a group of NAD⁺-dependent protein deacylases. They "erase" acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism. Human sirtuins have been intensely pursued by both academia and industry as therapeutic targets for a broad spectrum of diseases such as cancer, neurodegenerative diseases, and metabolic disorders. The last two decades have witnessed a flood of small molecule sirtuin regulators. However, there remain relatively few compounds targeting human sirtuins in clinical development. This reflects the inherent issues concerning the development of isoform-selective and potent molecules with good drug-like properties. In this article, small molecule sirtuin regulators that have advanced into clinical trials will be discussed in details as "successful" examples for future drug development. Special attention is given to the discovery of these compounds, the mechanism of action, pharmacokinetics analysis, formulation, as well as the clinical outcomes observed in the trials.

SUBMITTER: Curry AM

PROVIDER: S-EPMC8568457 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Human Sirtuin Regulators: The "Success" Stories.

Curry Alyson M AM White Dawanna S DS Donu Dickson D Cen Yana Y

Frontiers in physiology 20211021

The human sirtuins are a group of NAD<sup>+</sup>-dependent protein deacylases. They "erase" acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism. Human sirtuins have been intensely pursued by both academia and industry as therapeutic targets for a broad spectrum of di ...[more]

PMID: 34744791

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Project description:IntroductionThe onset of the COVID-19 pandemic halted in-person activities in universities and caused disruption in the usual iteration of the semesters. When the clinical environment resumed student placement, the potential health risks caused additional anxiety to the students and clinical faculty. This paper aims to examine the measures implemented to support the radiation therapy students during their first clinical placement during the COVID-19 pandemic.BackgroundThe 2nd year radiation therapy students' first clinical placement was organized around pandemic restrictions that required new activities to support student safety and wellness. The clinical faculty team redesigned the clinical course to integrate enhanced communication, additional safety measures and mental wellness sessions, as well as making COVID-19 related resources available during the week-long orientation and throughout the semester.MethodsRegistered students were asked to participate in a 9-item survey questionnaire to gather their perspective on the effectiveness of the orientation and clinical activities during the pandemic. The responses were tabulated and independently analyzed for emergent themes by the clinical faculty.DiscussionThe students reported that the combination of activities, workshops, exposure to the treatment unit and feedback from both clinical faculty and learning mentors provided the support needed for physical safety and wellness in the clinic. Identified challenges included communication with continuous masking, the timeliness of communicating evolving clinical safety protocols, and the need for enhanced coordination of interprofessional education.ConclusionThe COVID-19 pandemic brought new challenges and opportunities for students and clinical faculty at the University of Alberta's Radiation Therapy department. The results of the quality improvement survey highlighted the importance and effectiveness of the redesigned clinical course, which integrated COVID-19 related activities, enhanced communication strategies, safety, wellness resources and check-ins throughout the course.

Project description:BackgroundPeer narratives engage listeners through personally relevant content and have been shown to promote lifestyle change and effective self-management among patients with hypertension. Incorporating key quotations from these stories into follow-up text messages is a novel way to continue the conversation, providing reinforcement of health behaviors in the patients' daily lives.ObjectiveIn our previous work, we developed and tested videos in which African American Veterans shared stories of challenges and success strategies related to hypertension self-management. This study aims to describe our process for developing a text-messaging protocol intended for use after viewing videos that incorporate the voices of these Veterans.MethodsWe used a multistep process, transforming video-recorded story excerpts from 5 Veterans into 160-character texts. We then integrated these into comprehensive 6-month texting protocols. We began with an iterative review of story transcripts to identify vernacular features and key self-management concepts emphasized by each storyteller. We worked with 2 Veteran consultants who guided our narrative text message development in substantive ways, as we sought to craft culturally sensitive content for texts. Informed by Veteran input on timing and integration, supplementary educational and 2-way interactive assessment text messages were also developed.ResultsWithin the Veterans Affairs texting system Annie, we programmed five 6-month text-messaging protocols that included cycles of 3 text message types: narrative messages, nonnarrative educational messages, and 2-way interactive messages assessing self-efficacy and behavior related to hypertension self-management. Each protocol corresponds to a single Veteran storyteller, allowing Veterans to choose the story that most resonates with their own life experiences.ConclusionsWe crafted a culturally sensitive text-messaging protocol using narrative content referenced in Veteran stories to support effective hypertension self-management. Integrating narrative content into a mobile health texting intervention provides a low-cost way to support longitudinal behavior change. A randomized trial is underway to test its impact on the lifestyle changes and blood pressure of African American Veterans.Trial registrationClinicalTrials.gov NCT03970590; https://clinicaltrials.gov/ct2/show/NCT03970590.International registered report identifier (irrid)DERR1-10.2196/29423.

Dataset Information

Human Sirtuin Regulators: The "Success" Stories.

Publications

Human Sirtuin Regulators: The "Success" Stories.

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