Thrombospondin-1 modulation by Bifidobacterium spp. mitigates lung damage in an acute lung injury mouse model.

Unlabelled: Our study shows that Bifidobacterium spp. supplementation reduces lung damage in acute lung injury by enhancing immune cell activity and restoring thrombospondin-1 levels, offering a promising therapeutic approach for the treatment of ALI/ARDS.

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are critical conditions characterized by severe lung inflammation and damage, often exacerbated by mechanical ventilation.

Plasma EphA2 level is a superior biomarker to Del-1 for sepsis diagnosis and prognosis.

Background: Sepsis, characterized by a dysregulated host response to infection, often leads to organ dysfunction, and vascular endothelial dysfunction plays a central role. The erythropoietin-producing hepatocellular carcinoma (Eph)A2 receptor is associated with increased vascular permeability; however, the developmental endothelial locus-1 (Del-1), has contrasting effects on endothelial function. Hence, we examined their potential as biomarkers of sepsis.

Sepsis Diagnosis Based on a Parylene Matrix Chip Using LPC16:0 as a Biomarker in Comparison with Colorimetry of Total Phospholipid.

For the medical diagnosis of sepsis, it is crucial to differentiate infectious inflammation from noninfectious symptoms to prevent acute aggravation. Herein, a diagnosis for early stage sepsis was performed using LPC 16:0 and total phospholipids as small molecular biomarkers. The measurement of LPC 16:0 was conducted using a parylene matrix chip, which was developed to effectively detect small molecules in laser desorption/ionization mass spectrometry (LDI-MS).

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.

Electrochemical analysis of total phospholipids in human serum for severe sepsis diagnosis.

Electrochemical analysis of total phospholipids was performed for the diagnosis of sepsis. The influence of electrode materials on the analysis of the chromogenic substrate was analyzed using Au, graphite, and pyrolyzed carbon electrodes. The total phospholipid analysis based on electrochemical analysis with pyrolyzed carbon was used for diagnosis of sepsis using sera from healthy volunteers, systemic inflammatory response syndrome (SIRS), and severe sepsis patients.

Novel small molecule-mediated restoration of the surface expression and anion exchange activity of mutated pendrin causing Pendred syndrome and DFNB4.

Variants in SLC26A4 (pendrin) are the most common reasons for genetic hearing loss and vestibular dysfunction in East Asians. In patients with Pendred syndrome and DFNB4 (autosomal recessive type of genetic hearing loss 4), caused by variants in SLC26A4, the hearing function is residual at birth and deteriorates over several years, with no curative treatment for these disorders. In the present study, we revealed that a novel small molecule restores the expression and function of mutant pendrin.

Identification of Biomarkers for the Diagnosis of Sepsis-Associated Acute Kidney Injury and Prediction of Renal Recovery in the Intensive Care Unit.

Purpose: Acute kidney injury (AKI) following sepsis is associated with higher mortality; however, reliable biomarkers for AKI development and recovery remain to be elucidated.

Materials And Methods: Patients with sepsis admitted to the medical intensive care unit (ICU) of Severance Hospital between June 2018 and May 2019 were prospectively analyzed. Patients were divided into those with and without AKI within 48 hours.

TMED3 Complex Mediates ER Stress-Associated Secretion of CFTR, Pendrin, and SARS-CoV-2 Spike.

Under ER stress conditions, the ER form of transmembrane proteins can reach the plasma membrane via a Golgi-independent unconventional protein secretion (UPS) pathway. However, the targeting mechanisms of membrane proteins for UPS are unknown. Here, this study reports that TMED proteins play a critical role in the ER stress-associated UPS of transmembrane proteins.

NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model.

Background: For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model.

Methods: Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor.

Inhibition of Pendrin by a small molecule reduces Lipopolysaccharide-induced acute Lung Injury.

Pendrin is encoded by and its mutation leads to congenital hearing loss. Additionally, pendrin is up-regulated in inflammatory airway diseases such as chronic obstructive pulmonary disease, allergic rhinitis, and asthma. In this study, the effects of a novel pendrin inhibitor, YS-01, were investigated in an LPS-induced acute lung injury (ALI) mice model, and the mechanism underlying the effect of YS-01 was examined.

Diagnosis and mortality prediction of sepsis via lysophosphatidylcholine 16:0 measured by MALDI-TOF MS.

Sepsis remains a critical problem with high mortality worldwide, but there is still a lack of reliable biomarkers. We aimed to evaluate the serum lysophosphatidylcholine (LPC) 16:0 as a biomarker of sepsis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients admitted to intensive care unit at Severance Hospital from March 2017 through June 2018 were prospectively enrolled.

MALDI-TOF Mass Spectrometry Based on Parylene-Matrix Chip for the Analysis of Lysophosphatidylcholine in Sepsis Patient Sera.

In this work, medical diagnosis of sepsis was conducted via quantitative analysis of lysophosphatidylcholine 16:0 (LPC 16:0) by using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry based on a parylene-matrix chip. In the first step, specific mass peaks for the diagnosis of sepsis were searched by comparing MALDI-TOF mass spectra of sepsis patient sera with healthy controls and pneumonia patient sera. Two mass peaks at / = 496.

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.

Erythropoietin-Producing Hepatoma Receptor Tyrosine Kinase A2 Modulation Associates with Protective Effect of Prone Position in Ventilator-induced Lung Injury.

The erythropoietin-producing hepatoma (Eph) receptor tyrosine kinase A2 (EphA2) and its ligand, ephrinA1, play a pivotal role in inflammation and tissue injury by modulating the epithelial and endothelial barrier integrity. Therefore, EphA2 receptor may be a potential therapeutic target for modulating ventilator-induced lung injury (VILI). To support this hypothesis, here, we analyzed EphA2/ephrinA1 signaling in the process of VILI and determined the role of EphA2/ephrinA1 signaling in the protective mechanism of prone positioning in a VILI model.

Utility of Conventional Culture and MALDI-TOF MS for Identification of Microbial Communities in Bronchoalveolar Lavage Fluid in Comparison with the GS Junior Next Generation Sequencing System.

Background: Diverse microbiota exist in the lower respiratory tract. Although next generation sequencing (NGS) is the most widely used microbiome analysis technique, it is difficult to implement NGS in clinical microbiology laboratories. Therefore, we evaluated the performance of conventional culture methods together with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in identifying microbiota in bronchoalveolar lavage (BAL) fluid.

All-trans retinoic acid attenuates bleomycin-induced pulmonary fibrosis via downregulating EphA2-EphrinA1 signaling.

The role of all-trans retinoic acid (ATRA) in pulmonary fibrosis is relatively unknown, although this metabolite modulates cell differentiation, proliferation, and development. We aimed to evaluate the role of ATRA in bleomycin-induced pulmonary fibrosis, and whether the mechanism involves EphA2-EphrinA1 and PI3K-Akt signaling. We evaluated three groups of mice: a control group (intraperitoneal DMSO injection 3 times weekly after PBS instillation), bleomycin group (intraperitoneal DMSO injection 3 times weekly after bleomycin instillation), and bleomycin + ATRA group (intraperitoneal ATRA injection 3 times weekly after bleomycin instillation).

Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.

Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury.

EphA2 Receptor Signaling Mediates Inflammatory Responses in Lipopolysaccharide-Induced Lung Injury.

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury.

Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.