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Background@#We investigated whether metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with an elevated risk of all-cause and cardiovascular mortality using a large-scale health examination cohort. @*Methods@#A total of 394,835 subjects in the Kangbuk Samsung Health Study cohort were enrolled from 2002 to 2012. Participants were categorized by the presence of nonalcoholic fatty liver disease (NAFLD) and MAFLD as follows: normal subjects; patients with both NAFLD and MAFLD; patients with NAFLD only; and patients with MAFLD only. Cox proportional hazards models were used to analyze the risk of mortality. @*Results@#During a median 5.7 years of follow-up, 20.69% was patients with both NAFLD and MAFLD, 1.51% was patients with NAFLD only, and 4.29% was patients with MAFLD only. All-cause and cardiovascular death was higher in patients with MAFLD than those without MAFLD (P<0.001, respectively). In patients with MAFLD only, the hazard ratio (HR) of all-cause and cardiovascular death was 1.35 (95% confidence interval [CI], 1.13 to 1.60) and 1.90 (95% CI, 1.26 to 2.88) after adjusting for age, which lost its statistical significance by multivariable adjustments. Compared to patients with less than two components of metabolic dysfunction, patients with more than two components of metabolic dysfunction were a higher risk of cardiovascular death (HR, 2.05; 95% CI, 1.25 to 3.38) and only women with more than two components of metabolic dysfunction were a higher risk of all-cause death (HR, 1.44; 95% CI, 1.02 to 2.03). @*Conclusion@#MAFLD criteria could identify a high-risk group for all-cause and cardiovascular death.
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Background and Objectives@#To date, no studies have been conducted on the interaction between extracellular heat shock protein 70 (Hsp70) and C-X-C chemokine receptor type 4 (CXCR4) in the upper airway. We aimed to evaluate the relationship between extracellular Hsp70 and CXCR4 and their role in the primary human nasal epithelium. @*Methods@#We cultured primary human nasal epithelial (HNE) cells in an air–liquid interface. Macrogen performed single-cell quantitative polymerase chain reaction and sequencing. We conducted western blot analysis for the CXCR4 and mitogen-activated protein kinase (MAPK) pathways. @*Results@#Extracellular Hsp70 treatment significantly increased the genetic expression and protein levels of CXCR4 in primary HNE cells. Phospho-ERK expression was increased by cotreatment with Hsp70 and CXCL12, but inhibited by pretreatment with AMD3100, a CXCR4 inhibitor. Pretreatment with an anti-Hsp70 antibody reduced phospho-ERK expression upregulation induced by cotreatment with Hsp70 and CXCL12. @*Conclusion@#Extracellular Hsp70 participates in the activation of the CXCR4-dependent downstream signaling pathway in HNE cells. Further studies should evaluate the extracellular Hsp70-CXCL12/CXCR4 axis and the role of its components in the development of inflammatory diseases.
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Objective@#We aimed to investigate the longitudinal trends in prevalence of hypertriglyceridemia in Korean adults and hypertriglyceridemia-associated lifestyle habits, socioeconomic factors and comorbidities. @*Methods@#Data from the 2007–2020 Korea National Health and Nutrition Examination Survey (KNHANES) were used in this study. Two cutoff values (≥150 mg/dL and ≥200 mg/dL) for fasting serum triglyceride levels were used to estimate the age- and sex-specific prevalence of hypertriglyceridemia. Use of lipid-lowering medications, lifestyle factors such as smoking, alcohol consumption, and regular exercise, socioeconomic variables such as educational attainment and household income, and comorbidities such as obesity, abdominal obesity, hypertension, and diabetes mellitus were also investigated. @*Results@#The prevalence of hypertriglyceridemia among Koreans based on KNHANES 2007–2020 was 29.6% at ≥150 mg/dL and 16.1% at ≥200 mg/dL. While the rate of using lipidlowering medications increased steadily from 2007 to 2020, changes in annual prevalence of hypertriglyceridemia were subtle. The prevalence of hypertriglyceridemia in men peaked in middle age (47.7% and 30.0% for ≥150 mg/dL and ≥200 mg/dL, respectively, in their 40s), but its prevalence in women increased throughout their lifetime (32.6% and 14.7% for ≥150 mg/ dL and ≥200 mg/dL, respectively, in their 70s). Smoking and high-risk drinking exacerbated peak prevalence in both sexes. Young adults with any comorbidities had prominently increased prevalence of hypertriglyceridemia. The lowest levels of education and income were both associated with the higher prevalence of hypertriglyceridemia in both sexes. @*Conclusion@#It is important to understand the age- and sex-specific epidemiology of hypertriglyceridemia to establish its appropriate management plans.
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Background@#Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. @*Methods@#We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. @*Results@#Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. @*Conclusion@#The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.
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Background@#This study investigated the changes of fatty liver disease prevalence in general Korean population. @*Methods@#This study analyzed data from the Korean National Health Insurance Service from 2009 to 2017 that included individuals aged 20 years or older who had undergone a medical health examination. Fatty liver disease was assessed using the fatty liver index (FLI). The disease severity was defined by FLI cutoff, ≥30 as moderate, and ≥60 as severe fatty liver disease. @*Results@#The prevalence of Korean adults aged 20 years or over with fatty liver disease (FLI ≥60) increased from 13.3% in 2009 to 15.5% in 2017 (P for trend <0.001). The increase in fatty liver disease prevalence was prominent in men (from 20.5% to 24.2%) and the young age (20 to 39 years) group (from 12.8% to 16.4%) (P for interaction <0.001). The prevalence of fatty liver disease was the highest in type 2 diabetes mellitus (T2DM, 29.6%) population compared to that of prediabetes or normoglycemia (10.0% and 21.8%) in 2017. The prevalence of fatty liver disease had statistically increased in individuals with T2DM and prediabetes (P for trend <0.001). Its prevalence increased more steeply in the young-aged population with T2DM, from 42.2% in 2009 to 60.1% in 2017. When applying a lower FLI cutoff (≥30) similar results were observed. @*Conclusion@#The prevalence of fatty liver disease in the Korean population has increased. Individuals who are young, male, and have T2DM are vulnerable to fatty liver disease.
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Background and Objectives@#Fewer studies are available on geriatric patients’ gustatory dysfunction than on their olfactory dysfunction. Here we aimed to evaluate the relationship between subjective gustatory dysfunction and subjective or objective olfactory dysfunction according to cognitive function in geriatric patients.Subjects and Method We prospectively enrolled patients who underwent both cognitive function test and olfactory function test between August 2018 and May 2019. The correlation between subjective gustatory dysfunction and subjective olfactory dysfunction or conventional olfactory function scores was evaluated for geriatric patients with or withhout cognitive dysfunction. Participants with a threshold-discrimination-identification (TDI) score (<21) on the YSK olfactory function test were diagnosed with olfactory dysfunction. Subjective gustatory function and olfactory function were evaluated using the visual analog scale. The Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet and Mini-Mental State Examination were administered to all participants. Overall, 120 patients (27 male, 93 female; mean age, 73.00±7.50 years) were enrolled. @*Results@#We found that the subjective gustatory function score did not correlate with the threshold, discrimination, identification, or the summation of TDI scores of the olfactory function test but was significantly associated with the subjective olfactory function score (p<0.001). Further, there was no significant correlation between the subjective gustatory function score and cognitive function. @*Conclusion@#The subjective olfactory function score was the only factor significantly correlated with the subjective gustatory function score. Based on these results, we suggest evaluating gustatory function in geriatric patients with olfactory dysfunction.
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Background@#A total of 8,303 individuals (4.3%) with adverse reactions (n=191,860) after vaccination developed serious conditions or died. Such health developments could cause people not vaccinated yet or waiting for a booster shot to become fearful of the vaccination. @*Methods@#The 3-month (July–September 2021) clinical data of 41 patients from the family medicine department of a single medical center were analyzed retrospectively to determine risk factors and to investigate the clinical course to identify the cause of symptoms in detail. @*Results@#A significant number of older adults aged over 50 years reported experiencing general weakness (P=0.026) but fewer incidences of fever than patients aged 50 years or younger (P=0.011). Eighteen of the 41 patients were requested to visit more than twice or consult a specialist. In 14 patients, the symptoms were explained by other medical causes. @*Conclusion@#The primary physician has a pivotal role in thoroughly evaluating patients who complain of adverseeffects after vaccination, considering the broad multitude of symptoms and medical conditions presented. To thoroughlyevaluate and appropriately advise patients with adverse reactions to their chosen vaccine, taking detailedmedical history and nutritional counseling are required to identify possible underlying causes, resolve symptoms,and educate them on self-care and regarding vaccines.
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Foreign bodies pose a diagnostic challenge to clinicians, and nasal foreign bodies have the potential to lead to significant morbidity. Although foreign bodies in the nasal cavity are a commonly encountered problem in pediatric patients, a foreign body in the nasal cavity not associated with a trauma history is rare in adults. We recently experienced a 35-year-old man who presented with a foreign body in his right nasal cavity and anterior tooth pain. He was not sure what the material was, and we were not able to confirm the material type preoperatively. However, we found that a very large and thick material was impacted and totally obstructed the right anterior nasal cavity. We surgically removed it as a bone block and confirmed postoperatively that the material was glass. This case provided several lessons, and we would like to share our experience.
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Objective@#To validate the criteria for the extreme risk category for atherosclerotic cardiovascular disease (ASCVD). @*Methods@#An observational cohort study of 35,464 individuals with established ASCVD was performed using the National Health Information Database. Incident myocardial infarction (MI), ischemic stroke, and death in patients with established ASCVD was investigated to validate the criteria for the extreme risk category of ASCVD defined as the presence of diabetes mellitus (DM), chronic kidney disease (CKD), and history of premature ASCVD. @*Results@#Among 35,464 patients, 77.97% of them were classified into the extreme risk group of ASCVD. A total of 28.10%, 39.61%, and 32.12% had DM, CKD, and a history of premature ASCVD, respectively. During a mean follow-up of 8.39 years, MI, ischemic stroke, and all-cause death were found in 3.87%, 8.51%, and 23.98% of participants, respectively. In multivariate analysis, patients with DM had higher risk for MI (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.45–1.81), ischemic stroke (HR, 1.39; 95% CI, 1.29–1.50), and all-cause death (HR, 1.52; 95% CI, 1.45–1.59) than those without DM. Patients with CKD had 1.56 times higher risk for MI, 1.12 times higher risk for ischemic stroke, and 1.34 times higher risk for death than those without CKD. However, the risk for MI, ischemic stroke, and all-cause death was not different between patients with and without a history of premature ASCVD. @*Conclusion@#DM and CKD, but not a history of premature ASCVD, could be considered as reasonable criteria of an extreme risk for ASCVD.
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Background@#To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM). @*Methods@#We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age. @*Results@#Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m2. The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles. @*Conclusion@#In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.
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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorders and is associated with various metabolic diseases, including type 2 diabetes mellitus (T2DM). There are no approved drugs for NAFLD, and the only approved treatment option is weight reduction. However, it is not easy to maintain weight loss by lifestyle modification alone; pharmacological treatments are helpful in this regard. As insulin resistance plays an important role in the development of NAFLD, many antidiabetic drugs have been evaluated for treatment of NAFLD. Pioglitazone could be a first-line option to improve nonalcoholic steatohepatitis (NASH) in patients with T2DM to produce some improvement in fibrosis. Glucagon-like peptide-1 receptor agonists show evidence of improving NAFLD/NASH with fibrosis. Metformin and dipeptidyl peptidase-4 inhibitors are not recommended for treating NAFLD in patients with T2DM. Evidence that sodium-glucose cotransporter 2 inhibitors improve NAFLD/NASH with fibrosis in patients with T2DM is emerging.
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Background@#To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database. @*Methods@#We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes. @*Results@#The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m2 were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m2. Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM. @*Conclusion@#The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.
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BackgroundUmbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.MethodsInsulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.ResultsGlucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.ConclusionUC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.
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Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.
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Objectives@#. Few studies have reported combined analyses of the microbiome of the adenoids and tonsils in pediatric patients with snoring, and correlations of the adenotonsillar microbiome with clinical characteristics have not been evaluated to date. The aim of this study was to characterize the adenotonsillar microbiome and to determine its correlations with the subjective symptoms of pediatric patients with snoring and with levels of regional mucosal immune molecules. @*Methods@#. Twenty-four children who underwent tonsillectomy with adenoidectomy owing to snoring were enrolled in this cross-sectional study conducted between August 2017 and December 2018. The microbiome of the adenoids and tonsils was characterized, and its alpha- and beta-diversity was determined. Clinical characteristics, including subjective discomfort during sleep (assessed using the obstructive sleep apnea-18 questionnaire), the presence of allergic rhinitis, concentrations of heat shock protein (Hsp)27, Hsp70, and interleukin-8 (IL-8) in lavage fluids, and white blood cell (WBC) counts, were measured. @*Results@#. At the phylum level, the microbiome was not significantly different between the adenoids and tonsils; the alpha and beta indices were likewise not significantly different between these two regions. The alpha-diversity of the entire adenotonsillar microbiome was associated with sex, emotional stress, and IL-8 levels in the tonsil lavage fluids. Beta-diversity was associated with Hsp27 levels in the tonsil lavage fluids and WBC counts. Multiple allergen simultaneous test results were not significant, although total serum immunoglobulin E levels were significantly associated with the beta-diversity of the adenotonsillar microbiome. @*Conclusion@#. The data reported herein suggest, for the first time, that the adenotonsillar microbiome interacts with the regional mucosal immune system. The observed association of the microbiome with subjective discomfort is a novel finding that warrants further investigation.
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Background@#To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database. @*Methods@#We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes. @*Results@#The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m2 were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m2. Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM. @*Conclusion@#The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.
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BackgroundUmbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.MethodsInsulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.ResultsGlucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.ConclusionUC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.
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Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.
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Objectives@#. Few studies have reported combined analyses of the microbiome of the adenoids and tonsils in pediatric patients with snoring, and correlations of the adenotonsillar microbiome with clinical characteristics have not been evaluated to date. The aim of this study was to characterize the adenotonsillar microbiome and to determine its correlations with the subjective symptoms of pediatric patients with snoring and with levels of regional mucosal immune molecules. @*Methods@#. Twenty-four children who underwent tonsillectomy with adenoidectomy owing to snoring were enrolled in this cross-sectional study conducted between August 2017 and December 2018. The microbiome of the adenoids and tonsils was characterized, and its alpha- and beta-diversity was determined. Clinical characteristics, including subjective discomfort during sleep (assessed using the obstructive sleep apnea-18 questionnaire), the presence of allergic rhinitis, concentrations of heat shock protein (Hsp)27, Hsp70, and interleukin-8 (IL-8) in lavage fluids, and white blood cell (WBC) counts, were measured. @*Results@#. At the phylum level, the microbiome was not significantly different between the adenoids and tonsils; the alpha and beta indices were likewise not significantly different between these two regions. The alpha-diversity of the entire adenotonsillar microbiome was associated with sex, emotional stress, and IL-8 levels in the tonsil lavage fluids. Beta-diversity was associated with Hsp27 levels in the tonsil lavage fluids and WBC counts. Multiple allergen simultaneous test results were not significant, although total serum immunoglobulin E levels were significantly associated with the beta-diversity of the adenotonsillar microbiome. @*Conclusion@#. The data reported herein suggest, for the first time, that the adenotonsillar microbiome interacts with the regional mucosal immune system. The observed association of the microbiome with subjective discomfort is a novel finding that warrants further investigation.
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Tyrosine kinase inhibitors are widely used as targeted treatments for various malignancies. Sorafenib is an orally active tyrosine kinase inhibitor that blocks the signaling pathways of several growth factors. Its use is approved for various malignancies such as unresectable hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumors. Several adverse effects have been reported in the literature; however, cardiotoxicity is rare. We present a case of recurrent coronary vasospasm caused by short-term administration (5 days) of sorafenib. Since it caused refractory ischemia after re-administration, we had no choice but to stop the treatment.