The gasdermin family:emerging therapeutic targets in diseases

The gasdermin(GSDM)family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis.This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization,pyroptosis,and the follow-up inflammatory response,which are crucial self-defense mechanisms against irritants and infections.GSDMs have been implicated in a range of diseases including,but not limited to,sepsis,viral infections,and cancer,either through involvement in pyroptosis or independently of this process.The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases.Current strategies for inhibiting GSDMD primarily involve binding to GSDMD,blocking GSDMD cleavage or inhibiting GSDMD-N-terminal(NT)oligomerization,albeit with some off-target effects.In this review,we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis,elucidate the activation mechanisms of GSDMs,explore their associations with a range of diseases,and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

How to improve the care of septic patients following"Surviving Sepsis Campaign:International Guidelines for Management of Sepsis and Septic Shock 2021"?

The updated global adult sepsis guidelines(guideline-2021),released in October 2021 by the Surviving Sepsis Campaign(SSC),place increased emphasis on improving the care of patients with sepsis.These evidence-based guidelines,published in Critical Care Medicine[1]and Intensive Care Medicine,[2]reflect practices and recommendations for the treatment of sepsis and septic shock in adults and are revised regularly to account for new research.

Deletion of G protein-coupled receptor 116 enhances neutrophil function and aggravates lung injury in mice

Acute lung injury(ALI)globally afflicts over 3 million in-dividuals every year.It can eventually develop into acute respiratory distress syndrome(ARDS)with a high mortality of up to 40%.To date,ALI has been undertreated in terms of the feeble efficacy of clinical approaches and the lack of proven pharmacological targets.1 G protein-coupled re-ceptors(GPCRs),the promising targets of modern medi-cine,participate intensively in the regulation of human physiology and pathophysiology.Among them,Gpr116,which is expressed in alveolar epithelial cells and immune cells.

Promising gas therapies for severe COVID-19

The novel coronavirus disease 2019(COVID-19)pandemic is a worldwide catastrophe,thoroughly challenging the healthcare systems.A growing number of victims suffer from a remarkable acute respiratory distress syndrome(ARDS)that necessitates admission to the intensive care unit(ICU),but there are no satisfactory treatments.Various gas therapies including nitric oxide,ozone,hyperbaric oxygen,hydrogen,and heliox have been employed in the fight against the pandemic and have improved clinical outcomes.However,the potential roles of these gases in COVID-19 treatment need to be verified in well-designed randomized controlled trials.This paper reviews advances in gaseous therapy of COVID-19.