Association Between Plasma Granzyme B Levels, Organ Failure, and 28-Day Mortality Prediction in Patients with Sepsis.

: Sepsis is basically an inflammatory disease that involves the host's immune response. Granzyme B, a cytotoxic protease, has garnered attention for its involvement in modulating immune responses. This study aimed to elucidate the clinical implications of granzyme B in critically ill patients with sepsis, focusing on plasma granzyme B levels as a potential prognostic marker.

Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.

Repositioning of ezetimibe for the treatment of idiopathic pulmonary fibrosis.

Background: We previously identified ezetimibe, an inhibitor of Niemann-Pick C1-like intracellular cholesterol transporter 1 and European Medicines Agency-approved lipid-lowering agent, as a potent autophagy activator. However, its efficacy against pulmonary fibrosis has not yet been evaluated. This study aimed to determine whether ezetimibe has therapeutic potential against idiopathic pulmonary fibrosis.

Three-dimensional label-free morphology of CD8 + T cells as a sepsis biomarker.

Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality rate. The lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its management. We aimed to investigate the potential of three-dimensional label-free CD8 + T cell morphology as a biomarker for sepsis.

Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes.

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, the genetic mechanisms and target genes underlying these loci are largely unknown, as most risk-associated-variants might regulate gene expression in a context-specific manner. Here, we generated a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation.

Impairment of Mitochondrial ATP Synthesis Induces RIPK3-dependent Necroptosis in Lung Epithelial Cells During Lung Injury by Lung Inflammation.

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation.

Clinical value of full-length tryptophanyl-tRNA synthetase for sepsis detection in critically ill patients - A retrospective clinical assessment.

Objectives: Related innate immune system activation and diagnostic factors of sepsis are not fully understood. The aim of this study was to analyze the clinical value of full-length tryptophanyl-tRNA synthetase (WRS) induced through inflammatory stimuli for the detection of sepsis and prediction of mortality in critically ill patients.

Methods: This was a retrospective analysis of blood samples collected prospectively from patients in the medical intensive care unit (ICU) at Yonsei University College of Medicine, from March 2015 to June 2018.

Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality.

As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes.

The ratio of plasma angiopoietin-2 to angiopoietin-1 as a prognostic biomarker in patients with sepsis.

Background: We aimed to investigate the role of angiopoietin (Angpt) as a predictive biomarker for sepsis by evaluating associations between plasma Angpt and various inflammatory cytokines and mortality in critically ill patients with sepsis.

Methods: This study was a retrospective cohort study of the prospectively collected samples and clinical data of 145 patients with sepsis who were admitted to the medical intensive care unit (ICU) of a 2000-bed university tertiary referral hospital in South Korea. We collected plasma within 24 h of medical ICU admission, and several biomarkers (Angpt-1 and -2, Tie2, vascular endothelial growth factor, interleukin (IL)-1β, IL-10, IL-18, IL-6, interferon gamma-induced protein-10, and tumor necrosis factor-α) were measured using a Human Magnetic Luminex Screening Assay kit.

The Effects of Retinoic Acid and MAPK Inhibitors on Phosphorylation of Smad2/3 Induced by Transforming Growth Factor β1.

Background: Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1.

Methods: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors.

Inhibition of insulin-like growth factor receptor-1 reduces necroptosis-related markers and attenuates LPS-induced lung injury in mice.

Insulin-like growth factor-1 (IGF-1) levels are known to increase in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome. Herein, we investigated the role of IGF-1 in lipopolysaccharide (LPS)-induced lung injury. In LPS-treated cells, expressions of receptor-interacting protein 3 (RIP3) and phosphorylated mixed lineage kinase domain-like protein (MLKL) were decreased in IGF-1 receptor small interfering RNA (siRNA)-treated cells compared to control cells.

Clinical implications of the plasma EphA2 receptor level in critically ill patients with septic shock.

The Eph/ephrin receptor ligand system is known to play a role in inflammation induced by infection, injury, and inflammatory diseases. The present study aimed to evaluate plasma EphA2 receptor levels in critically ill patients with sepsis. This study was a prospective cohort study evaluating samples and clinical data from the medical intensive care unit (MICU) of a 2000-bed university tertiary referral hospital in South Korea.

Relationship between vitamin D-binding protein polymorphisms and blood vitamin D level in Korean patients with COPD.

Background: In chronic obstructive pulmonary disease (COPD), the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD.

Methods: The study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort.

Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions.

Background: The development of chemo-resistance in non-small lung cancer is a major obstacle in treating patients. Hypoxia is a commonly faced microenvironment in solid tumor and suggested to be related to both autophagy and chemo-resistance.

Methods: In this study, we investigated the role of hypoxia-induced autophagy in acquiring chemo-resistance in both cancer cell (A549) and human cancer tissue

Results: Hypoxic exposure (1 % O2) of A549 cell stimulated autophagic induction in cancer cells, shown by increase of LC3BI to LC3BII conversion and decrease of p62/sequestosome1 in Western blot, increased GFP-LC puncta in confocal microscopy, and increased number of double-membrane autophagic vacuoles in electron micrographs.

Autophagy activity in pulmonary metastatic tumor tissues from colorectal cancer: a pilot study.

Purpose: Autophagy has been reported to be involved in treatment failure in tumor. We aimed to evaluate autophagy activity in tumor tissue and compare them between the recurrence and non-recurrence groups.

Materials And Methods: We analyzed expressions of autophagy-related proteins in tumor tissues which were obtained from pulmonary metastases of colorectal cancer patients by Western blot.

Relationship of vitamin D binding protein polymorphisms and lung function in Korean chronic obstructive pulmonary disease.

Purpose: Multiple genetic factors are associated with chronic obstructive pulmonary disease (COPD). The association of gene encoding vitamin D binding protein (VDBP, GC) with COPD has been controversial. We sought to investigate the types of GC variants in the Korean population and determine the association of GC variants with COPD and lung function in the Korean population.

The prevalence of human papillomavirus infection in Korean non-small cell lung cancer patients.

Human papillomavirus (HPV) infection is a co-carcinogen of lung cancer and contributes to its pathogenesis. To evaluate the prevalence of HPV infection, polymerase chain reaction (PCR) was employed to detect HPV 16, 18, and 33 DNA in tumor tissues of 112 patients with non-small cell lung cancer (NSCLC) who underwent curative surgery from Jan. 1995 to Dec.

Identical epidermal growth factor receptor mutations in adenocarcinomatous and squamous cell carcinomatous components of adenosquamous carcinoma of the lung.

Background: Adenosquamous carcinoma of the lung is composed of adenocarcinomatous and squamous cell carcinomatous components. The epidermal growth factor receptor (EGFR) mutations occur mostly in adenocarcinomas and rarely in squamous cell carcinoma of lung. Attempts to investigate the EGFR mutation status in each component of adenosquamous carcinoma and to characterize the patients according to mutation status may help to understand the histogenesis of adenosquamous carcinoma.

Identification of tumor suppressor loci on the long arm of chromosome 5 in pulmonary large cell neuroendocrine carcinoma.

Background: A recent cytogenetic analysis of non-small cell lung cancer revealed hot-spot regions for deletion on the long arm of chromosome 5 and suggested the existence of putative tumor suppressor genes in that region. However, similar studies on genetic alterations in large cell neuroendocrine carcinoma (LCNEC) have been very limited. To our knowledge, this is the first report to screen for the loss of heterozygosity (LOH) and to examine the location of putative tumor suppressor genes on chromosome 5q in LCNEC.

Promoter -202 A/C polymorphism of insulin-like growth factor binding protein-3 gene and non-small cell lung cancer risk.

Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits the mitogenic and antiapoptotic activity of insulin-like growth factor (IGF) by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene.

Identification of tumor suppressor loci on the long arm of chromosome 15 in primary small cell lung cancer.

Small cell lung cancer (SCLC) frequently shows a loss of heterozygosity (LOH) on chromosome 15q. In order to define the commonly affected region on chromosome 15q, we tested 23 primary SCLCs by microsatellite analysis. By analyzing 43 polymorphic microsatellite markers located on chromosome 15q, we found that 14 (60.