Sialyl Lewis Glycomimetics as E- and P-Selectin Antagonists Targeting Hyperinflammation.

Inflammatory disorders, such as sepsis, pancreatitis, and severe COVID-19, often cause immune dysfunction and high mortality. These conditions trigger excessive immune cell influx, leading to cytokine storms, organ damage, and compensatory immune suppression that results in immunoparalysis, organ dysfunction, and reinfection. Controlled and reversible immunosuppression limiting immune cell recruitment to inflammation sites could reduce hyperinflammation and prevent immune exhaustion.

Sialyl Lewis glycomimetics bearing an extended anionic chain targeting E- and P- selectin binding sites.

Neutrophil binding to vascular P- and E-selectin is the rate-limiting step in the recruitment of immune cells to sites of inflammation. Many diseases, including sickle cell anemia, post-myocardial infarction reperfusion injury, and acute respiratory distress syndrome are characterized by dysregulated inflammation. We have recently reported sialyl Lewis analogues as potent antagonists of P- and E-selectin and demonstrated their in vivo immunosuppressive activity.

Digital interventions to reduce social isolation and loneliness in older adults: An evidence and gap map.

Background: Social isolation and loneliness are more common in older adults and are associated with a serious impact on their well-being, mental health, physical health, and longevity. They are a public health concern highlighted by the COVID-19 pandemic restrictions, hence the need for digital technology tools to enable remotely delivered interventions to alleviate the impact of social isolation and loneliness during the COVID-19 restrictions.

Objectives: To map available evidence on the effects of digital interventions to mitigate social isolation and/or loneliness in older adults in all settings except hospital settings.

Synthesis of Sialyl Lewis Mimetics with E- and P-Selectin Binding Properties and Immunosuppressive Activity.

E- and P-selectins are adhesion proteins implicated in immune cell recruitment at sites of infection, making them important drug targets for diseases involving excessive and uncontrolled inflammation. In this study, we developed an efficient strategy to synthesize bicyclic galactopyranosides through a key stereoselective equatorial C4-propiolate addition and TMSCN axial C-glycosidation. The nitrile group can then be converted to the carboxyl and different bioisosteres at a late stage in the synthesis, allowing for various derivatizations to potentially enhance biological activity.

PROTOCOL: Digital interventions to reduce social isolation and loneliness in older adults: An evidence and gap map.

This is the protocol for a Campbell systematic review. The objectives are as follows: the aim is to map available evidence on the effects of digital interventions to mitigate social isolation and/or loneliness in older adults in all settings except hospital settings.