Novel Poxin Stable cGAMP-Derivatives Are Remarkable STING Agonists.

2',3'-cGAMP is a cyclic A- and G-containing dinucleotide second messenger, which is formed upon cellular recognition of foreign cytosolic DNA as part of the innate immune response. The molecule binds to the adaptor protein STING, which induces an immune response characterized by the production of type I interferons and cytokines. The development of STING-binding molecules with both agonistic as well as antagonistic properties is currently of tremendous interest to induce or enhance antitumor or antiviral immunity on the one hand, or to treat autoimmune diseases on the other hand. To escape the host innate immune recognition, some viruses encode poxin endonucleases that cleave 2',3'-cGAMP. Here we report that dideoxy-2',3'-cGAMP (1) and analogs thereof, which lack the secondary ribose-OH groups, form a group of poxin-stable STING agonists. Despite their reduced affinity to STING, particularly the compound constructed from two A nucleosides, dideoxy-2',3'-cAAMP (2), features an unusually high antitumor response in mice.

Perivascular Fat: A Novel Risk Factor for Coronary Artery Disease.

Perivascular adipose tissue (PVAT) interacts with the vascular wall and secretes bioactive factors which regulate vascular wall physiology. Vice versa, vascular wall inflammation affects the adjacent PVAT via paracrine signals, which induce cachexia-type morphological changes in perivascular fat. These changes can be quantified in pericoronary adipose tissue (PCAT), as an increase in PCAT attenuation in coronary computed tomography angiography images. Fat attenuation index (FAI), a novel imaging biomarker, measures PCAT attenuation around coronary artery segments and is associated with coronary artery disease presence, progression, and plaque instability. Beyond its diagnostic capacity, PCAT attenuation can also ameliorate cardiac risk stratification, thus representing an innovative prognostic biomarker of cardiovascular disease (CVD). However, technical, biological, and anatomical factors are weakly related to PCAT attenuation and cause variation in its measurement. Thus, to integrate FAI, a research tool, into clinical practice, a medical device has been designed to provide FAI values standardized for these factors. In this review, we discuss the interplay of PVAT with the vascular wall, the diagnostic and prognostic value of PCAT attenuation, and its integration as a CVD risk marker in clinical practice.

Obesity and Infection: What Have We Learned From the COVID-19 Pandemic.

Objective: The critical role played by the nutritional status in the complications, duration of hospitalization and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) has emerged from several research studies in diverse populations. Obesity has been associated with an increased risk of serious complications, as the adipose tissue appears to have significant effects on the immune response. The aim of this narrative review was to investigate the relationship between COVID-19 and obesity. Methods: We performed a review of papers in the English language derived from PubMed, Science Direct, and Web of Science. The primary outcomes investigated were the severity of the disease, admission to the intensive care unit (ICU), need for intubation, and mortality. Results and Conclusion: Review of 44 eligible studies from 18 countries around the world revealed evidence that obesity increases the risk of severe COVID-19 complications, ICU admission, intubation and mortality. Patients with a higher body mass index (BMI) appear to be more vulnerable to SARS-CoV-2 infection, with more severe illness requiring admission to ICU and intubation, and to have higher mortality. A healthy body weight should be targeted as a long-term prevention measure against acute complications of infection, and in the event of COVID-19, overweight and obese patients should be monitored closely.