Publications by authors named "Kuei-Pin Chung"

Obesity is a risk factor for acute respiratory distress syndrome (ARDS). We previously showed that obesity is linked to increased lung injury and bronchoalveolar lavage fluid (BALF) fatty acids in a hyperoxic model of ARDS. We sought to expand our understanding of this association and examined the effect of obesity on β-oxidation (FAO), the mitochondrial process of breaking down fatty acids, in alveolar epithelial type 2 cells (AEC2s) in hyperoxia-induced ARDS.

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Background: Laboratory examinations play a crucial role in medical diagnostics and treatment, necessitating the identification of interference factors to ensure accurate results. Biotin, a common dietary supplement, can interfere with immunoassays utilizing biotin-streptavidin interactions. Studies have documented biotin's significant impact on thyroid function tests and various immunoassays, prompting the need for effective mitigation strategies.

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Background: Triglycerides (TGs) play a crucial role in various physiological processes through the breakdown of their fatty acyl (FA) side chains. It has been demonstrated that not only the total levels of TGs but also the specific composition of FA side chains are vital for biological functions. However, biomedical studies that comprehensively identify FA compositions remain very limited.

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Objective : Recent studies have proposed that Krebs cycle metabolites may serve as potential biomarkers for prognosis in sepsis. However, whether these metabolites are associated with disease severity and can be applied to improve the effectiveness of current prognosis assessment in sepsis remains unclear and is explored in this study. Methods : This prospective multicenter cohort study was conducted in medical intensive care units (ICUs).

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Background: High-flow nasal cannula (HFNC) has emerged as a promising intervention for postextubation oxygen therapy, with the potential to reduce the need for reintubation. However, it remains unclear whether using a higher flow setting provides better outcomes than the commonly used flow rate of 30 to 50 L/min.

Research Question: Does setting the flow rate of HFNC at 60 L/min vs 40 L/min for postextubation care result in different extubation outcomes?

Study Design And Methods: This randomized controlled trial assigned intubated patients to receive HFNC at either a 60 L/min or 40 L/min flow rate following extubation.

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Article Synopsis
  • Type 2 alveolar epithelial (AT2) cells play a key role in managing inflammation in the lungs after injury, and their function may be affected by poor mitochondrial fatty acid metabolism.
  • The expression of an enzyme called CPT1a, crucial for fatty acid breakdown in these cells, is notably reduced in conditions like acute respiratory distress syndrome (ARDS).
  • Deleting Cpt1a or related enzymes in AT2 cells can limit inflammation in lung injury by decreasing the production of a specific inflammatory signal (CXCL2), suggesting that impaired fatty acid metabolism serves as an anti-inflammatory mechanism in ARDS.
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  • Cell-free DNA (cfDNA) released from injured cells can worsen inflammation, and COVID-19 patients often face severe respiratory issues requiring oxygen therapy or mechanical ventilation.
  • This study analyzed cfDNA levels in 95 hospitalized COVID-19 patients to see if these levels could predict the need for treatment.
  • Findings showed that higher levels of cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) were linked to a greater need for oxygen therapy or mechanical ventilation, suggesting these could be early biomarkers for assessing patient severity.
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Background: Secondary pneumonia has a significant clinical impact on critically ill patients with COVID-19.

Aim: Considering potential geographic variations, this study explores the clinical implications of secondary pneumonia within East Asian populations.

Methods: This multicenter, retrospective cohort study enrolled critical COVID-19 patients requiring intensive care units (ICUs) admission in Taiwan from December 31, 2020, to June 1, 2022.

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Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit.

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  • AEC2 cells play a crucial role in lipid metabolism for surfactant production, which is vital for lung function.
  • Chronic exposure to cigarette smoke disrupts lipid synthesis in these cells and is connected to the development of COPD.
  • Mice lacking the FASN enzyme in AEC2 cells showed increased lung inflammation and altered surfactant composition, highlighting the enzyme's importance in how the lung responds to smoke exposure.
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  • Intracellular purine- and pyrimidine-related derivatives are crucial for genetic preservation, energy production, and signaling in cells, and this study focused on quantifying these molecules.
  • A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, which included adding medronic acid and ammonium phosphate to improve measurement accuracy, especially for di- and triphosphate nucleotides.
  • The validated method showed strong accuracy and precision, and was effectively used to analyze changes in these derivatives in A549 cells under mitochondrial stress, potentially paving the way for new drug developments targeting purine and pyrimidine metabolism.
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Heat shock protein (HSP) 40 has emerged as a key factor in both innate and adaptive immunity, whereas the role of HLJ1, a molecular chaperone in HSP40 family, in modulating endotoxin-induced sepsis severity is still unclear. During lipopolysaccharide (LPS)-induced endotoxic shock, HLJ1 knockout mice shows reduced organ injury and IFN-γ (interferon-γ)-dependent mortality. Using single-cell RNA sequencing, we characterize mouse liver nonparenchymal cell populations under LPS stimulation, and show that HLJ1 deletion affected IFN-γ-related gene signatures in distinct immune cell clusters.

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Background: Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission and is activated by phosphorylation at serine 616. We previously demonstrated that DRP1 activation is regulated by epidermal growth factor receptor (EGFR) signaling and multiple kinases in lung adenocarcinoma, and is significantly associated with an increased risk of postoperative recurrence in early stage lung adenocarcinoma. However, it is unclear whether DRP1 activation is associated with worse prognosis in patients with advanced lung adenocarcinoma.

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Recent studies revealed the role of dynamin-related protein 1 (DRP1), encoded by the DNM1L gene, in regulating the growth of cancer cells of various origins. However, the regulation, function, and clinical significance of DRP1 remain undetermined in lung adenocarcinoma. Our study shows that the expression and activation of DRP1 are significantly correlated with proliferation and disease extent, as well as an increased risk of postoperative recurrence in stage I to stage IIIA lung adenocarcinoma.

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Background: Acute respiratory distress syndrome (ARDS) is heterogeneous. As an indication of the heterogeneity of ARDS, there are patients whose syndrome improves rapidly (i.e.

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Mitophagy, by maintaining mitochondrial quality control, plays a key role in maintaining kidney function and is impaired in pathologic states. Macrophages are well known for their pathogenic role in kidney fibrosis. Here, we report that PINK1/Parkin-mediated mitophagy in macrophages is compromised in experimental and human kidney fibrosis.

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Accumulating evidence illustrates a fundamental role for mitochondria in lung alveolar type 2 epithelial cell (AEC2) dysfunction in the pathogenesis of idiopathic pulmonary fibrosis. However, the role of mitochondrial fusion in AEC2 function and lung fibrosis development remains unknown. Here we report that the absence of the mitochondrial fusion proteins mitofusin1 (MFN1) and mitofusin2 (MFN2) in murine AEC2 cells leads to morbidity and mortality associated with spontaneous lung fibrosis.

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  • Recent research indicates that higher levels of acylcarnitines in patients with sepsis are linked to worse survival outcomes, but their specific role in measuring sepsis severity needs more exploration.
  • This study involved collecting and analyzing plasma samples from sepsis patients in ICUs across Taiwan, focusing on the levels of carnitine and acylcarnitines using advanced liquid chromatography techniques.
  • Findings revealed that increased plasma acetylcarnitine levels were strongly associated with multiple organ dysfunction, blood culture positivity, and a significantly higher risk of death within 28 days, emphasizing its potential as a prognostic marker in sepsis.
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Renal fibrosis is a common pathogenic response to injury in chronic kidney disease (CKD). The receptor-interacting protein kinase-3 (RIPK3), a regulator of necroptosis, has been implicated in disease pathogenesis. In mice subjected to unilateral ureteral obstruction-induced (UUO-induced) or adenine diet-induced (AD-induced) renal fibrosis, models of progressive kidney fibrosis, we demonstrate increased kidney expression of RIPK3.

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Studies about prognostic assessment in cancer patients requiring prolonged mechanical ventilation (PMV) for post-intensive care are scarce. We retrospectively enrolled 112 cancer patients requiring PMV support who were admitted to the respiratory care center (RCC), a specialized post-intensive care weaning facility, from November 2009 through September 2013. The weaning success rate was 44.

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  • The study reveals that NADPH oxidase 4 (NOX4) plays a crucial role in inflammation and metabolism, specifically affecting the innate immune response by influencing fatty acid oxidation (FAO) through carnitine palmitoyltransferase 1A (CPT1A).
  • NOX4 deficiency leads to reduced FAO, which in turn decreases the activation of the NLRP3 inflammasome in macrophages, although it does not affect other inflammasomes like NLRC4, NLRP1, and AIM2.
  • In experiments with Nox4-deficient mice, researchers observed decreased production of pro-inflammatory cytokines and improved survival in infections, indicating that
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Patients with rheumatoid arthritis (RA) often have pulmonary involvement, and interstitial lung disease (ILD) is the primary manifestation, in which diffuse alveolar damage (DAD) is a rare histopathologic pattern. Leflunomide (LEF) is a frequently prescribed disease-modifying antirheumatic drug for treating RA. LEF-related ILD in the form of DAD has been reported in patients with RA, with the duration of LEF treatment before symptom onset ranging from 6 to 1204 days.

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Liver kinase B1 (LKB1) is a tumor suppressor, and its loss might lead to activation of the mammalian target of rapamycin (mTOR) and tumorigenesis. This study aimed to determine the clinical relevance of LKB1 gene and protein expression in breast cancer patients. LKB1 protein expression was evaluated using immunohistochemistry in tumors from early breast cancer patients in two Taiwanese medical centers.

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Sepsis-related mortality has been found increased in RAG-1 knockout mice. However, in patients admitted to medical intensive care units, it is unknown whether severe lymphocyte depletion at admission is associated with increased interleukin (IL)-7 and IL-15 levels in circulation, and increased mortality. We prospectively enrolled 92 patients who were admitted to medical intensive care units for severe sepsis or septic shock.

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