Kyubo Kim

Bio: Kyubo Kim is an academic researcher from Hallym University. The author has contributed to research in topics: Mucus & Slow-wave sleep. The author has an hindex of 5, co-authored 11 publications receiving 456 citations. Previous affiliations of Kyubo Kim include Yonsei University & University of Texas MD Anderson Cancer Center.

Mucus hypersecretion in asthma: causes and effects.

Abstract: Purpose of reviewAirway mucus plugging has long been recognized as a principal cause of death in asthma. However, molecular mechanisms of mucin overproduction and secretion have not been understood until recently. These mechanisms are reviewed together with ongoing investigations relating them to lu

SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages

Abstract: Proper regulation of mitophagy for mitochondrial homeostasis is important in various inflammatory diseases. However, the precise mechanisms by which mitophagy is activated to regulate inflammatory ...

Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract.

Abstract: Background The submucosal gland (SMG) is important in the control of airway surface fluid. Protease-activated receptor (PAR) 2 contributes to the pathophysiology of allergies in response to nonspecific allergens bearing proteases and anion secretion. House dust mites (HDMs) have abundant proteases that can activate PAR2, but little is known about the direct effect of HDM on SMG secretion. Objective The aim of this study was to investigate the effect of HDMs on glandular secretion and its mechanism in allergic patients, patients with chronic rhinosinusitis (CRS), or both. Methods Inferior nasal turbinates were harvested from 55 patients and classified into 4 groups (the control, allergic rhinitis [AR], CRS, and AR+CRS groups). A microscope attached to a digital camera was used to quantify mucus bubbles from individual SMGs while stimulated with HDM extract, PAR2-activating peptide, and carbachol. PAR2 expression in the SMG was determined by means of immunostaining with anti-PAR2 mAb. Results HDM induced a significantly higher secretion rate and number of responding glands in the AR and AR+CRS groups than in the control group. Interestingly, patients in the CRS group, who had no HDM-specific IgE antibody, showed a higher response than the control group, and its response was suppressed by a PAR2-selective antagonist. The responses to PAR2-activating peptide were similar to those to HDM, and their secretion rates positively correlated with HDM responses. PAR2 was highly expressed in all 3 disease groups with immunostaining. Conclusions HDM allergens can induce glandular secretion in patients with AR, CRS, or both, and PAR2 represents a possible mechanism for nonspecific hyperreactivity in inflammatory airway diseases.

The Updated AJCC/TNM Staging System for Papillary Thyroid Cancer (8th Edition): From the Perspective of Genomic Analysis.

Abstract: Recently, the American Joint Committee on Cancer published the 8th edition of its Cancer Staging Manual with major changes regarding the staging of thyroid cancer, including the raising of the age cutoff from 45 to 55 years. Using the clinical and genetic data of 505 papillary thyroid cancer (PTC) cases, we aimed to compare overall survival (OS) and recurrence-free survival (RFS) with different age cutoff values, and also investigate the efficacy of the new staging system on a genomic level. We downloaded gene expression data, somatic mutation profile, copy number alteration data and clinical data of 505 PTC patients from The Cancer Genome Atlas data portal. We used multiple statistical analysis and multiplatform genomic analysis to evaluate the efficacy of the 8th edition. When using 55 years as the cutoff value for analyzing RFS, the Kaplan–Meier plot showed a significant p value but not when using 45 years (p = 0.006 vs. p = 0.493), but both cutoff values were significant when analyzing OS (p = 1.1 × 10−9 with age 55 vs. p = 4.4 × 10−5 with age 45). When looking at stage-dependent survival, both the 7th and 8th edition had significant p values (p = 0.048 vs. p = 3.1 × 10−9 in RFS and p = 5.9 × 10−10 vs. p = 2.2 × 10−10 in OS). Multiplatform genomic analysis showed patients ≥55 years had 103 differently expressed genes when compared with other age groups. Signaling pathway analysis revealed that patients ≥55 years had altered pathways associated with aggressiveness of thyroid cancer. In conclusion, this is the first study to show clinical and genetic evidence supporting the altered age cutoff point of 55 years in the AJCC 8th edition for PTC patients.

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Molecular mechanisms and physiological functions of mitophagy.

Abstract: Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy-mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady-state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations.

Inflammasome activation and regulation: toward a better understanding of complex mechanisms.

Abstract: Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by a repertoire of endogenous and exogenous stimuli, leading to enzymatic activation of canonical caspase-1, noncanonical caspase-11 (or the equivalent caspase-4 and caspase-5 in humans) or caspase-8, resulting in secretion of IL-1β and IL-18, as well as apoptotic and pyroptotic cell death. Appropriate inflammasome activation is vital for the host to cope with foreign pathogens or tissue damage, while aberrant inflammasome activation can cause uncontrolled tissue responses that may contribute to various diseases, including autoinflammatory disorders, cardiometabolic diseases, cancer and neurodegenerative diseases. Therefore, it is imperative to maintain a fine balance between inflammasome activation and inhibition, which requires a fine-tuned regulation of inflammasome assembly and effector function. Recently, a growing body of studies have been focusing on delineating the structural and molecular mechanisms underlying the regulation of inflammasome signaling. In the present review, we summarize the most recent advances and remaining challenges in understanding the ordered inflammasome assembly and activation upon sensing of diverse stimuli, as well as the tight regulations of these processes. Furthermore, we review recent progress and challenges in translating inflammasome research into therapeutic tools, aimed at modifying inflammasome-regulated human diseases.

PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation.

Abstract: Contrast-induced acute kidney injury (CI-AKI) occurs in more than 30% of patients after intravenous iodinated contrast media and causes serious complications, including renal failure and mortality. Recent research has demonstrated that routine antioxidant and alkaline therapy failed to show benefits in CI-AKI patients with high risk for renal complications. Mitophagy is a mechanism of selective autophagy, which controls mitochondrial quality and mitochondrial reactive oxygen species (ROS) through degradation of damaged mitochondria. The role of mitophagy and its regulation of apoptosis in CI-AKI are poorly understood. In this study, we demonstrated that mitophagy was induced in renal tubular epithelial cells (RTECs) during CI-AKI, both in vivo and in vitro. Meanwhile, contrast media-induced mitophagy was abolished when silencing PINK1 or PARK2 (Parkin), indicating a dominant role of the PINK1-Parkin pathway in mitophagy. Moreover, mitochondrial damage, mitochondrial ROS, RTEC apoptosis, and renal injury under contrast exposure were more severe in PINK1- or PARK2-deficient cells and mice than in wild-type groups. Functionally, PINK1-Parkin-mediated mitophagy prevented RTEC apoptosis and tissue damage in CI-AKI through reducing mitochondrial ROS and subsequent NLRP3 inflammasome activation. These results demonstrated that PINK1-Parkin-mediated mitophagy played a protective role in CI-AKI by reducing NLRP3 inflammasome activation.

Th9 and allergic disease.

Abstract: Helper CD4(+) T-cell subsets have improved our understanding of adaptive immunity in humans and in animal models of disease. These include T helper type 1 (Th1), Th2 and the interleukin-17 (IL-17) -producing population 'Th17'. Th2 cells have been described as orchestrating the immune response in allergic disease based on studies with patient samples and animal models. The cytokine IL-9 has largely been regarded as a Th2 cytokine that makes multifocal contributions to allergic disease. Recent data suggest that under certain conditions relevant to chronic disease (IL-4 and transforming growth factor-beta), a distinct population of IL-9-producing 'Th9' helper T cells can exist. The contribution of Th9 cells in allergic disease is currently unknown, and this review will propose a model for how these cells may regulate chronic allergic inflammation.