Integrative function of histone deacetylase 3 in inflammation.

Inflammation is a complex biological response triggered when an organism encounters internal or external stimuli. These triggers activate various signaling pathways, leading to the release of numerous inflammatory mediators aimed at the affected tissue. Ensuring precision and avoiding the excessive activation, the inflammatory process is subject to tight regulation. Histone deacetylase 3 (HDAC3), a member of class I HDACs family, stands out for its significant role in modulating various inflammatory signaling, including Nuclear Factor kappa B (NF-κB) signaling, Mitogen-activated protein kinase (MAPK) signaling and Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling. In this review, we illuminate the intricate molecular mechanisms of HDAC3 across these inflammatory pathways. We emphasize its importance in orchestrating a balanced inflammatory response and highlight its promising potential as a therapeutic target.

Deacetylase-dependent and -independent role of HDAC3 in cardiomyopathy.

Cardiomyopathy is a common disease of cardiac muscle that negatively affects cardiac function. HDAC3 commonly functions as corepressor by removing acetyl moieties from histone tails. However, a deacetylase-independent role of HDAC3 has also been described. Cardiac deletion of HDAC3 causes reduced cardiac contractility accompanied by lipid accumulation, but the molecular function of HDAC3 in cardiomyopathy remains unknown. We have used powerful genetic tools in Drosophila to investigate the enzymatic and nonenzymatic roles of HDAC3 in cardiomyopathy. Using the Drosophila heart model, we showed that cardiac-specific HDAC3 knockdown (KD) leads to prolonged systoles and reduced cardiac contractility. Immunohistochemistry revealed structural abnormalities characterized by myofiber disruption in HDAC3 KD hearts. Cardiac-specific HDAC3 KD showed increased levels of whole-body triglycerides and increased fibrosis. The introduction of deacetylase-dead HDAC3 mutant in HDAC3 KD background showed comparable results with wild-type HDAC3 in aspects of contractility and Pericardin deposition. However, deacetylase-dead HDAC3 mutants failed to improve triglyceride accumulation. Our data indicate that HDAC3 plays a deacetylase-independent role in maintaining cardiac contractility and preventing Pericardin deposition as well as a deacetylase-dependent role to maintain triglyceride homeostasis.

Impact of COVID-19 Pandemic on Non-Small Cell Lung Cancer Care.

We assessed the impact of COVID-19 on healthcare visits, timing of stage IV NSCLC diagnosis and immunotherapy initiation, and rates of switching to extended dosing schedules of immunotherapies among patients with stage IV NSCLC. This retrospective study examined electronic health record data of adult patients receiving treatment for stage IV NSCLC within The US Oncology Network and Onmark. Endpoints were compared for February-July 2019 (before COVID) vs. February-July 2020 (during COVID). The study found rapid decreases in numbers of patients with clinic/vital visits, immunotherapy initiations, and new diagnoses of stage IV NSCLC during April-May 2020 vs. April-May 2019. The rate of delays of immunotherapy administrations and proportions of patients with such delays increased from February to March of 2020. These patterns may have resulted from the increase in COVID-19 cases during this period and the corresponding quarantine and lockdowns. However, when comparing pre COVID-19 and during COVID-19 for May and after, the differences in delay of immuno-oncology administrations became less marked, likely due to lifting of lockdowns. The rate of switching from shorter to longer dosing schedules increased from May-July 2020. This was mainly attributed to pembrolizumab, likely due to FDA approval of the pembrolizumab 6W dosing schedule in April 2020.