The role of platelets in sepsis: A review.

Sepsis, a life-threatening condition characterized by organ dysfunction, results from a complex series of pathophysiological mechanisms including immune dysfunction, an uncontrolled inflammatory response, and coagulation abnormalities. It is a major contributor to global mortality and severe disease development. Platelets, abundant in the circulatory system, are sensitive to changes in the body's internal environment and are among the first cells to respond to dysregulated pro-inflammatory and pro-coagulant reactions at the onset of sepsis. In the initial stages of sepsis, the coagulation cascade, inflammatory response, and endothelial tissue damage perpetually trigger platelet activation. These activated platelets then engage in complex inflammatory and immune reactions, potentially leading to organ dysfunction. Therefore, further research is essential to fully understand the role of platelets in sepsis pathology and to develop effective therapeutic strategies targeting the associated pathogenic pathways. This review delves into the involvement of platelets in sepsis and briefly outlines the clinical applications of associated biomarkers.

THE IL-33/ST2 AXIS PROMOTES ACUTE RESPIRATORY DISTRESS SYNDROME BY NATURAL KILLER T CELLS.

ABSTRACT: Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled inflammation, which manifests as leukocyte infiltration and lung injury. However, the molecules that initiate this infiltration remain incompletely understood. We evaluated the effect of the nuclear alarmin IL-33 on lung damage and the immune response in LPS-induced lung injury. We established a LPS-induced lung injury mouse model. We used genetically engineered mice to investigate the relationship among the IL-33/ST2 axis, NKT cells, and ARDS. We found that IL-33 was localized to the nucleus in alveolar epithelial cells, from which it was released 1 h after ARDS induction in wild-type (WT) mice. Mice lacking IL-33 (IL-33 - / - ) or ST2 (ST2 - / - ) exhibited reduced neutrophil infiltration, alveolar capillary leakage, and lung injury in ARDS compared with WT mice. This protection was associated with decreased lung recruitment and activation of invariant nature killer (iNKT) cells and activation of traditional T cells. Then, we validated that iNKT cells were deleterious in ARDS in CD1d - / - and Vα14Τg mice. Compared with WT mice, Vα14Τg mice exhibited increased lung injury in ARDS, and the CD1d - / - mice showed outcomes opposite those of the Vα14Τg mice. Furthermore, we administered a neutralizing anti-ST2 antibody to LPS-treated WT and Vα14Τg mice 1 h before LPS administration. We found that IL-33 promoted inflammation through NKT cells in ARDS. In summary, our results demonstrated that the IL-33/ST2 axis promotes the early uncontrolled inflammatory response in ARDS by activating and recruiting iNKT cells. Therefore, IL-33 and NKT cells may be therapeutic target molecules and immune cells, respectively, in early ARDS cytokine storms.

The role of lung macrophages in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is an acute and diffuse inflammatory lung injury in a short time, one of the common severe manifestations of the respiratory system that endangers human life and health. As an innate immune cell, macrophages play a key role in the inflammatory response. For a long time, the role of pulmonary macrophages in ARDS has tended to revolve around the polarization of M1/M2. However, with the development of single-cell RNA sequencing, fate mapping, metabolomics, and other new technologies, a deeper understanding of the development process, classification, and function of macrophages in the lung are acquired. Here, we discuss the function of pulmonary macrophages in ARDS from the two dimensions of anatomical location and cell origin and describe the effects of cell metabolism and intercellular interaction on the function of macrophages. Besides, we explore the treatments for targeting macrophages, such as enhancing macrophage phagocytosis, regulating macrophage recruitment, and macrophage death. Considering the differences in responsiveness of different research groups to these treatments and the tremendous dynamic changes in the gene expression of monocyte/macrophage, we discussed the possibility of characterizing the gene expression of monocyte/macrophage as the biomarkers. We hope that this review will provide new insight into pulmonary macrophage function and therapeutic targets of ARDS.

Mechanism of Endoplasmic Reticulum Stress Pathway in the Osteogenic Phenotypic Transformation of Aortic Valve Interstitial Cells.

Background and Purpose: Calcific Aortic Valve Disease (CAVD) is a crucial component of degenerative valvular disease in old age and with the increasing prevalence of the aging population. we hope that by modeling valvular osteogenesis and intervening with endoplasmic reticulum stress inhibitor TUDCA to observe the effect of endoplasmic reticulum stress on valve osteogenesis. Methods: In this study, rabbit heart valvular interstitial cells (VICs) were isolated and cultured. They treated with ox-LDL (Oxidized Low Density Lipoprotein) stimulation to establish a model of valvular osteogenic transformation. BMP2 (Bone Morphogenetic Protein 2), PERK (Protein kinase R-like endoplasmic reticulum kinase), CHOP (CCAAT/enhancer-binding protein homologous protein) and transcriptional regulatory factor ATF4 (Activating Transcription Factor 4 )were recorded after intervention with ER stress inhibitor TUDCA. The effects of er stress on valvular osteogenic transformation were analyzed. Result: After stimulation of VICs with ox-LDL, the expression levels of BMP2, PERK, CHOP, and ATF4 increased. However, TUDCA treatment can alleviate the increased expression levels of BMP2, PERK ATF4, and CHOP under ox-LDL stimulation to a certain extent. Conclusion: The endoplasmic reticulum stress signaling pathway is involved in ox-LDL-induced calcification of rabbit valve interstitial cells. Inhibition of endoplasmic reticulum stress using TUDCA can improve the progression of rabbit aortic valve calcification.