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1.
Eur J Med Res ; 29(1): 338, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890718

ABSTRACT

BACKGROUND: Synaptotagmin 11 (SYT11) plays a pivotal role in neuronal vesicular trafficking and exocytosis. However, no independent prognostic studies have focused on various cancers. In this study, we aimed to summarize the clinical significance and molecular landscape of SYT11 in various tumor types. METHODS: Using several available public databases, we investigated abnormal SYT11 expression in different tumor types and its potential clinical association with prognosis, methylation profiling, immune infiltration, gene enrichment analysis, and protein-protein interaction analysis, and identified common pathways. RESULTS: TCGA and Genotype-Tissue Expression (GTEx) showed that SYT11 was widely expressed across tumor and corresponding normal tissues. Survival analysis showed that SYT11 expression correlated with the prognosis of seven cancer types. Additionally, SYT11 mRNA expression was not affected by promoter methylation, but regulated by certain miRNAs and associated with cancer patient prognosis. In vitro experiments further verified a negative correlation between the expression of SYT11 and miR-19a-3p in human colorectal, lung, and renal cancer cell lines. Moreover, aberrant SYT11 expression was significantly associated with immune infiltration. Pathway enrichment analysis revealed that the biological and molecular processes of SYT11 were related to clathrin-mediated endocytosis, Rho GTPase signaling, and cell motility-related functions. CONCLUSIONS: Our results provide a clear understanding of the role of SYT11 in various cancer types and suggest that SYT11 may be of prognostic and clinical significance.


Subject(s)
MicroRNAs , Neoplasms , Synaptotagmins , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Line, Tumor , DNA Methylation , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasms/genetics , Neoplasms/metabolism , Prognosis , Synaptotagmins/genetics , Synaptotagmins/metabolism
2.
Clin Exp Reprod Med ; 51(2): 163-169, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38263588

ABSTRACT

OBJECTIVE: This retrospective study aimed to investigate the prevalence of chronic endometritis, diagnosed using CD138 immunohistochemistry, among infertile women and to assess the association between chronic endometritis and recurrent implantation failure (RIF). METHODS: In total, 266 patients who underwent hysteroscopy due to infertility between 2019 and 2020 were included in the analysis. Of these, 136 patients with RIF and 130 non-RIF patients were included in the study. CD138 immunohistochemistry test results, blood biomarkers (including natural killer cells, white blood cells, and the lymphocyte-to-neutrophil ratio), and data on pregnancy outcomes were obtained. If the CD138 test yielded a positive result, the patients received antibiotic treatment. RESULTS: The overall proportion of CD138-positive patients was 32.7% (87/266). The CD138 positivity rate was not related to the number of cycles with implantation failure. In the RIF patient group, no significant associations were found between CD138 positivity and peripheral blood markers. The clinical pregnancy rates were similar between infertile women treated with antibiotics for chronic endometritis and those without chronic endometritis. CONCLUSION: To improve the pregnancy rate in infertile patients, it may be helpful to combine CD138 testing with other laboratory tests and administer antibiotic treatment if the result is positive.

3.
BMB Rep ; 56(11): 612-617, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37817442

ABSTRACT

Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells. [BMB Reports 2023; 56(11): 612-617].


Subject(s)
Cell Cycle Proteins , RNA-Binding Proteins , Humans , RNA-Binding Proteins/metabolism , Cell Cycle Proteins/metabolism , HeLa Cells , Nuclear Proteins/metabolism , Cell Proliferation/genetics , Genomic Instability , Endoplasmic Reticulum Stress , Apoptosis/genetics , Cell Line, Tumor , Intracellular Signaling Peptides and Proteins/metabolism
4.
Nat Commun ; 14(1): 4047, 2023 Jul 08.
Article in English | MEDLINE | ID: mdl-37422498

ABSTRACT

The pulverization of lithium metal electrodes during cycling recently has been suppressed through various techniques, but the issue of irreversible consumption of the electrolyte remains a critical challenge, hindering the progress of energy-dense lithium metal batteries. Here, we design a single-ion-conductor-based composite layer on the lithium metal electrode, which significantly reduces the liquid electrolyte loss via adjusting the solvation environment of moving Li+ in the layer. A Li||Ni0.5Mn0.3Co0.2O2 pouch cell with a thin lithium metal (N/P of 2.15), high loading cathode (21.5 mg cm-2), and carbonate electrolyte achieves 400 cycles at the electrolyte to capacity ratio of 2.15 g Ah-1 (2.44 g Ah-1 including mass of composite layer) or 100 cycles at 1.28 g Ah-1 (1.57 g Ah-1 including mass of composite layer) under a stack pressure of 280 kPa (0.2 C charge with a constant voltage charge at 4.3 V to 0.05 C and 1.0 C discharge within a voltage window of 4.3 V to 3.0 V). The rational design of the single-ion-conductor-based composite layer demonstrated in this work provides a way forward for constructing energy-dense rechargeable lithium metal batteries with minimal electrolyte content.


Subject(s)
Body Fluids , Lithium , Electrolytes , Ions , Metals
5.
COPD ; 20(1): 153-161, 2023 12.
Article in English | MEDLINE | ID: mdl-37036446

ABSTRACT

This study aimed to evaluate the prevalence, trends, and risk factors of early chronic obstructive pulmonary disease (COPD) by using a nationally representative sample. The datasets of the Korea National Health and Nutrition Examination Survey 2010-2019 were used, where 80,860 individuals were identified; of these, 9,045 participants aged 40-49 years who underwent spirometry with no missing data were analyzed. Early COPD was defined as forced expiratory volume in 1 s /forced vital capacity ratio < the lower limit of normal (2.5th percentile) in individuals aged <50 years without a history of asthma, inhaler therapy, or persistent respiratory symptoms. The prevalence and trend of early COPD were estimated according to features such as smoking status and pack-years. Joinpoint regression analysis was used to analyze the significant annual change in the trend according to sex, smoking status, and pack-years. A complex sample multivariable-adjusted regression model was used to identify factors affecting early COPD. The estimated population size during 2010-2019 was 82,326,178. Early COPD was present in 4.5% of patients (6.5% of men and 2.3% of women). It was present in 7.7% of current smokers, followed by former and never smokers. Among smokers with ≥ 10 pack-years, early COPD was present in 8.2%, whereas it was present in 2.6% of smokers with < 10 pack-years. Joinpoint regression analyses found a recent decrease in the trend of prevalence in males who were former and current smokers. The multivariable-adjusted logistic regression model showed that being male, lower educational level, smoking status, and pack-years were factors that affected the presence of early COPD. Continued surveillance of this pre-disease condition is required, and further research are warrant.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Male , Female , Nutrition Surveys , Prevalence , Risk Factors , Smoking/adverse effects , Forced Expiratory Volume , Vital Capacity , Spirometry
6.
Pharmaceuticals (Basel) ; 15(11)2022 Oct 31.
Article in English | MEDLINE | ID: mdl-36355519

ABSTRACT

Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from eczema, itching, disrupted barrier function and aberrant cutaneous immune responses. The aim of the present study was to assess the efficacy of kushenol F as an effective treatment for AD via the suppression of thymic stromal lymphopoietin (TSLP) production. The results of the present study demonstrated that the clinical symptoms of AD were less severe and there was reduced ear thickening and scratching behavior in kushenol F-treated Dermatophagoides farinae extract (DFE)/1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Histopathological analysis demonstrated that kushenol F decreased the DFE/DNCB-induced infiltration of eosinophil and mast cells and TSLP protein expression levels. Furthermore, kushenol F-treated mice exhibited significantly lower concentrations of serum histamine, IgE and IgG2a compared with the DFE/DNCB-induced control mice. Kushenol F also significantly decreased phosphorylated NF-κB and IKK levels and the mRNA expression levels of IL-1ß and IL-6 in cytokine combination-induced human keratinocytes. The results of the present study suggested that kushenol F may be a potential therapeutic candidate for the treatment of AD via reducing TSLP levels.

7.
Exp Mol Med ; 54(8): 1188-1200, 2022 08.
Article in English | MEDLINE | ID: mdl-35982301

ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation and the destruction of joints and systemic organs. RA is commonly accompanied by neuropsychiatric complications, such as cognitive impairment and depression. However, the role of monoamine oxidase (MAO) and its inhibitors in controlling neurotransmitters associated with these complications in RA have not been clearly identified. Here, we report that peripheral and central MAO-B are highly associated with joint inflammation and cognitive impairment in RA, respectively. Ribonucleic acid (RNA) sequencing and protein expression quantification were used to show that MAO-B and related molecules, such as gamma aminobutyric acid (GABA), were elevated in the inflamed synovium of RA patients. In primary cultured fibroblast-like synoviocytes in the RA synovium, MAO-B expression was significantly increased by tumor necrosis factor (TNF)-α-induced autophagy, which produces putrescine, the polyamine substrate for GABA synthesis. We also observed that MAO-B-mediated aberrant astrocytic production of GABA was augmented by interleukin (IL)-1ß and inhibited CA1-hippocampal pyramidal neurons, which are responsible for memory storage, in an animal model of RA. Moreover, a newly developed reversible inhibitor of MAO-B ameliorated joint inflammation by inhibiting cyclooxygenase (Cox)-2. Therefore, MAO-B can be an effective therapeutic target for joint inflammation and cognitive impairment in patients with RA.


Subject(s)
Arthritis, Rheumatoid , Cognitive Dysfunction , Animals , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Cells, Cultured , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Fibroblasts/metabolism , Inflammation/metabolism , Monoamine Oxidase/metabolism , Monoamine Oxidase/pharmacology , Tumor Necrosis Factor-alpha/metabolism , gamma-Aminobutyric Acid/metabolism
8.
Article in English | MEDLINE | ID: mdl-35886249

ABSTRACT

(1) Background: To evaluate the association between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) in the general population using a nationally representative sample from South Korea; (2) Methods: This study included 4275 adults aged ≥40 years who completed the snoring, tiredness, observed apnea, high blood pressure, body mass index (BMI), age, neck circumference, and gender (STOP-Bang) questionnaire. The risk of OSA was stratified into low, intermediate, and high grades according to the STOP-Bang score. The prevalence of NAFLD according to the STOP-Bang score was calculated, and the increasing trend was measured. A complex sample multivariable regression analysis with adjustments for possible confounding variables was used to calculate the odds ratio of NAFLD and advanced fibrosis. Subgroup analysis was conducted with stratification based on sex and obesity status; (3) Results: We identified 1021 adults with NAFLD and 3254 adults without NAFLD. The prevalence of NAFLD increased significantly with higher STOP-Bang scores in both men and women. Participants of both sexes with high STOP-Bang scores were more likely to have NAFLD. Compared to non-obese individuals, the risk of NAFLD according to the STOP-Bang score was more intense in obese individuals. With respect to hepatic steatosis, there was no significant association between advanced fibrosis and STOP-Bang score; (4) Conclusions: OSA, the risk of which was measured using the STOP-Bang model, was closely associated with NAFLD in both Korean men and women. Clinicians should consider screening for NAFLD in individuals with a high STOP-Bang score.


Subject(s)
Non-alcoholic Fatty Liver Disease , Sleep Apnea, Obstructive , Adult , Cross-Sectional Studies , Female , Fibrosis , Humans , Male , Mass Screening , Non-alcoholic Fatty Liver Disease/epidemiology , Obesity , Polysomnography/methods , Sleep Apnea, Obstructive/diagnosis , Surveys and Questionnaires
9.
BMJ Open ; 12(7): e062617, 2022 07 25.
Article in English | MEDLINE | ID: mdl-35879016

ABSTRACT

OBJECTIVES: Determination of reference intervals (RIs) using big data faces several obstacles due to heterogeneity in analysers, period and ethnicity. The present study aimed to establish the RIs for routine common blood count (CBC) and biochemistry laboratory tests in homogeneous, healthy, male Korean soldiers in their 20s using a large health check-up data set, comparing parametric and non-parametric estimation. DESIGN: A multicentre, cross-sectional study. SETTING: Seven armed forces hospitals in South Korea. PARTICIPANTS: A total of 609 649 men underwent health examination when promoted to corporal between January 2015 and September 2021. 260 889 eligible individuals aged 20-25 were included in the analysis. MAIN OUTCOMES AND MEASURES: The RIs were established by parametric and non-parametric methods. In the parametric approach, maximum likelihood estimation was applied to measure the Box-Cox transformation parameter and the values at the 2.5th and 97.5th percentiles were recalculated. The non-parametric approach adopted the Tukey's exclusion test and the values at the 2.5th and 97.5th percentiles were obtained. Classification by body mass index was also performed. RESULTS: The obtained RIs for haematology parameters were comparable between devices. If the values followed a Gaussian distribution, parametric and non-parametric methods were well matched for haematology and biochemical markers. When the values were right-skewed, the upper limits were higher with parametric than with non-parametric methods. Participants with obesity showed higher RIs for CBC, some liver function tests and some lipid profiles than participants without obesity. CONCLUSIONS: Using data from healthy, male Korean soldiers in their 20s, we proposed the RIs for CBC and biochemical parameters, comparing parametric and non-parametric estimation. As such approaches based on large data sets become more prevalent, further studies are needed to discriminate eligible individuals and determine RIs in an extrapolated sample.


Subject(s)
Military Personnel , Asian People , Cross-Sectional Studies , Humans , Male , Obesity , Reference Values
10.
Int J Mol Sci ; 23(10)2022 May 18.
Article in English | MEDLINE | ID: mdl-35628458

ABSTRACT

Mitophagy is a selective form of autophagy that removes damaged mitochondria. Increasing evidence indicates that dysregulated mitophagy is implicated in numerous autoimmune diseases, but the role of mitophagy in rheumatoid arthritis (RA) has not yet been reported. The aim of the present study was to determine the roles of mitophagy in patient-derived RA synovial fibroblasts (RASFs) and in the collagen antibody-induced arthritis mouse model. We measured the mitophagy marker PTEN-induced putative kinase 1 (PINK1) in RASFs treated with tumor necrosis factor-α (TNF-α) using Western blotting and immunofluorescence. Arthritis was induced in PINK1-/- mice by intraperitoneal injection of an anti-type II collagen antibody cocktail and lipopolysaccharide. RA severity was assessed by histopathology. PINK1 expression and damaged mitochondria increased in TNF-α treated RASFs via increased intracellular levels of reactive oxygen species. PINK1 knockdown RASFs decreased cellular migration and invasion functions. In addition, PINK1-/- mice with arthritis exhibited markedly reduced swelling and inflammation relative to wild-type mice with arthritis. Taken together, these findings suggest that regulation of PINK1 expression in RA could represent a potential therapeutic and diagnostic target for RA.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Synovitis , Animals , Antibodies , Fibroblasts/metabolism , Humans , Mice , Mice, Knockout , Mitophagy , Protein Kinases/genetics , Protein Kinases/metabolism , Tumor Necrosis Factor-alpha/pharmacology
11.
Am J Clin Pathol ; 158(2): 206-211, 2022 08 04.
Article in English | MEDLINE | ID: mdl-35285877

ABSTRACT

OBJECTIVES: Various preanalytical factors, including the collection tube, storage conditions, and centrifugation, affect the detection results of plasma cell-free DNA (cfDNA). We compared the effect of different centrifugation protocols on the detection of EGFR mutations in cfDNA. METHODS: We analyzed 117 plasma specimens from 110 patients with non-small cell lung cancer using the cobas EGFR Mutation Test v2 (Roche Diagnostics). We compared the identified EGFR mutations and semiquantitative index values from the 1- and 2-step centrifugation groups and confirmed the clinical impact of differences in the results after further high-speed centrifugation. RESULTS: We detected EGFR mutations in 44 (37.6%) and 47 (40.2%) samples that were centrifuged once and twice, respectively; the 2 groups showed an 89.7% (105/117) concordance and a strong correlation in their semiquantitative index values (r = 0.929). Among the 12 inconsistent result pairs, 9 samples of 2-step centrifugation (75%) were consistent with the results of a recent tissue biopsy. CONCLUSIONS: Additional high-speed centrifugation has been shown to increase the sensitivity of EGFR mutation detection in a commercial in vitro diagnostic real-time polymerase chain reaction device and is an optimal preanalytical factor for detecting low-allele frequency gene mutations using low concentrations of cfDNA.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cell-Free Nucleic Acids , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell-Free Nucleic Acids/genetics , Centrifugation , ErbB Receptors/genetics , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Reagent Kits, Diagnostic
13.
Vaccines (Basel) ; 9(12)2021 Dec 13.
Article in English | MEDLINE | ID: mdl-34960219

ABSTRACT

The immune-acquired responses after vaccination vary depending on the type of vaccine and the individual. The purpose of this study was to investigate the relationship between the acquisition of immunity and the side effects, health status, and lifestyle after completion of the second dose of AZD1222. Blood samples were collected after a second dose of AZD1222. The Euroimmun Anti-SARS-CoV-2 ELISA (IgG) for anti-S1 antibody, the cPASS SARS-CoV-2 neutralizing antibody detection kit for the surrogate virus neutralization test, and the T-spot Discovery SARS-CoV-2 kit were used to identify cellular immunogenicity. Patient experience of adverse effects was investigated using questionnaires. Information on health status and lifestyle were collected from the most recent health checkup data. Generally, females experience more reactogenicity in both intensity and duration. The rash of the first shot and chills of the second shot were associated with humoral immunity. However, comprehensive adverse effects had no correlation with humoral and cellular immunity. The T-spot-positive group had a higher creatinine level, which reflects muscle mass, than the T-spot-negative group. Males presented a higher level of T-spot assays. Body mass index and age were negatively correlated with the T-spot assay and anti-S1 antibody, respectively. Immune acquisition after the second AZD1222 shot was not associated with reactogenicity. However, individuals' sex, age, and BMI were found to be associated with immunogenicity after vaccination.

14.
Biomedicines ; 9(11)2021 Nov 19.
Article in English | MEDLINE | ID: mdl-34829956

ABSTRACT

Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC.

15.
Exp Mol Med ; 53(3): 432-445, 2021 03.
Article in English | MEDLINE | ID: mdl-33731895

ABSTRACT

Cancer cachexia is a highly debilitating condition characterized by weight loss and muscle wasting that contributes significantly to the morbidity and mortality of pancreatic cancer. The factors that induce cachexia in pancreatic cancer are largely unknown. We previously showed that pancreatic adenocarcinoma upregulated factor (PAUF) secreted by pancreatic cancer cells is responsible for tumor growth and metastasis. Here, we analyzed the relation between pancreatic cancer-derived PAUF and cancer cachexia in mice and its clinical significance. Body weight loss and muscle weight loss were significantly higher in mice with Panc-1/PAUF tumors than in those with Panc-1/Mock tumors. Direct administration of rPAUF to muscle recapitulated tumor-induced atrophy, and a PAUF-neutralizing antibody abrogated tumor-induced muscle wasting in Panc-1/PAUF tumor-bearing mice. C2C12 myotubes treated with rPAUF exhibited rapid inactivation of Akt-Foxo3a signaling, resulting in Atrogin1/MAFbx upregulation, myosin heavy chain loss, and muscle atrophy. The neutrophil-to-lymphocyte ratio and body weight loss were significantly higher in pancreatic cancer patients with high PAUF expression than in those with low PAUF expression. Analysis of different pancreatic cancer datasets showed that PAUF expression was significantly higher in the pancreatic cancer group than in the nontumor group. Analysis of The Cancer Genome Atlas data found associations between high PAUF expression or a high DNA copy number and poor overall survival. Our data identified tumor-secreted circulating PAUF as a key factor of cachexia, causing muscle wasting in mice. Neutralizing PAUF may be a useful therapeutic strategy for the treatment of pancreatic cancer-induced cachexia.


Subject(s)
Adenocarcinoma/complications , Biomarkers, Tumor/metabolism , Cachexia/pathology , Gene Expression Regulation, Neoplastic , Intercellular Signaling Peptides and Proteins/metabolism , Muscular Atrophy/pathology , Pancreatic Neoplasms/complications , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cachexia/etiology , Cachexia/metabolism , Cell Proliferation , Female , Humans , Male , Mice , Middle Aged , Muscular Atrophy/etiology , Muscular Atrophy/metabolism , Prognosis , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
16.
Dev Cell ; 56(8): 1118-1130.e6, 2021 04 19.
Article in English | MEDLINE | ID: mdl-33761320

ABSTRACT

Adenosine N6-methylation (m6A) is one of the most pervasive mRNA modifications, and yet the physiological significance of m6A removal (demethylation) remains elusive. Here, we report that the m6A demethylase FTO functions as a conserved regulator of motile ciliogenesis. Mechanistically, FTO demethylates and thereby stabilizes the mRNA that encodes the master ciliary transcription factor FOXJ1. Depletion of Fto in Xenopus laevis embryos caused widespread motile cilia defects, and Foxj1 was identified as one of the major phenocritical targets. In primary human airway epithelium, FTO depletion also led to FOXJ1 mRNA destabilization and a severe loss of ciliated cells with an increase of neighboring goblet cells. Consistently, Fto knockout mice showed strong asthma-like phenotypes upon allergen challenge, a result owing to defective ciliated cells in the airway epithelium. Altogether, our study reveals a conserved role of the FTO-FOXJ1 axis in embryonic and homeostatic motile ciliogenesis.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Cilia/metabolism , Demethylation , Forkhead Transcription Factors/genetics , Organogenesis , RNA Stability/genetics , RNA, Messenger/genetics , Adenosine/analogs & derivatives , Adenosine/metabolism , Animals , Asthma/pathology , Ciliopathies/pathology , Embryo, Mammalian/metabolism , Forkhead Transcription Factors/metabolism , Gene Expression Regulation , Humans , Mice, Inbred C57BL , Mice, Knockout , Phenotype , RNA, Messenger/metabolism , Respiratory Mucosa/metabolism , Xenopus laevis
18.
PLoS One ; 15(8): e0237983, 2020.
Article in English | MEDLINE | ID: mdl-32822397

ABSTRACT

OBJECTIVES: Although smoking is known to have a negative impact in patients with metabolic syndrome (MetS), only a few studies have examined the association between electronic cigarette (e-cig) use and MetS. METHODS: Among 22,948 participants in the 6th Korea National Health and Nutrition Examination Survey, 14,738 (13,459 [91.3%] never, 954 [6.5%] ever, and 325 [2.2%] current e-cig users) were selected. The relationship between e-cig exposure and MetS (based on the National Cholesterol Education Program Adult Treatment Panel [NCEP-ATP] III criteria) was evaluated using a multivariable logistic regression analysis. An unweighted analysis was performed to evaluate this association without a sampling weight. A subgroup analysis was performed among active smokers to compare dual users with never e-cig users. RESULTS: Among current e-cig users, 85.0% were dual users, 12.7% were former cigarette users, and 2.2% were only e-cig users. After adjustment for covariates, abdominal obesity and hypertriglyceridemia were significantly associated with current e-cig exposure (odds ratio [OR]: 1.88, 95% confidence interval [CI]: 1.41-2.50 and OR: 1.32, 95% CI: 1.00-1.74 respectively [compared with the never e-cig users group]). Compared with never e-cig users, current e-cig users showed an OR of 1.27 (95% CI: 0.96-1.70, Ptrend = 0.01) for MetS. In the unweighted analysis, the OR for MetS in current e-cig users was 1.40 (95% CI: 1.08-1.81, Ptrend <0.01). Compared with never e-cig users, dual users showed a higher OR for abdominal obesity (OR: 1.71, 95% CI: 1.25-2.34, Ptrend <0.001). CONCLUSIONS: Current e-cig exposure was associated with an increased risk of MetS. Dual use of e-cigs and cigarettes was associated with abdominal obesity. Further longitudinal studies and better assessment of e-cig use and type are needed to clarify this relationship.


Subject(s)
Metabolic Syndrome/pathology , Vaping , Adult , Cholesterol, HDL/blood , Cigarette Smoking , Female , Humans , Hypertriglyceridemia/epidemiology , Hypertriglyceridemia/pathology , Logistic Models , Male , Metabolic Syndrome/epidemiology , Middle Aged , Nutrition Surveys , Obesity/epidemiology , Obesity/pathology , Odds Ratio , Republic of Korea/epidemiology , Triglycerides/blood
19.
Asian-Australas J Anim Sci ; 33(12): 1912-1921, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32819072

ABSTRACT

OBJECTIVE: This study assessed genomic prediction accuracies based on different selection methods, evaluation procedures, training population (TP) sizes, heritability (h2) levels, marker densities and pedigree error (PE) rates in a simulated Korean beef cattle population. METHODS: A simulation was performed using two different selection methods, phenotypic and estimated breeding value (EBV), with an h2 of 0.1, 0.3, or 0.5 and marker densities of 10, 50, or 777K. A total of 275 males and 2,475 females were randomly selected from the last generation to simulate ten recent generations. The simulation of the PE dataset was modified using only the EBV method of selection with a marker density of 50K and a heritability of 0.3. The proportions of errors substituted were 10%, 20%, 30%, and 40%, respectively. Genetic evaluations were performed using genomic best linear unbiased prediction (GBLUP) and single-step GBLUP (ssGBLUP) with different weighted values. The accuracies of the predictions were determined. RESULTS: Compared with phenotypic selection, the results revealed that the prediction accuracies obtained using GBLUP and ssGBLUP increased across heritability levels and TP sizes during EBV selection. However, an increase in the marker density did not yield higher accuracy in either method except when the h2 was 0.3 under the EBV selection method. Based on EBV selection with a heritability of 0.1 and a marker density of 10K, GBLUP and ssGBLUP_0.95 prediction accuracy was higher than that obtained by phenotypic selection. The prediction accuracies from ssGBLUP_0.95 outperformed those from the GBLUP method across all scenarios. When errors were introduced into the pedigree dataset, the prediction accuracies were only minimally influenced across all scenarios. CONCLUSION: Our study suggests that the use of ssGBLUP_0.95, EBV selection, and low marker density could help improve genetic gains in beef cattle.

20.
PLoS One ; 15(7): e0236274, 2020.
Article in English | MEDLINE | ID: mdl-32722695

ABSTRACT

Mortality at an early stage after kidney transplantation is a catastrophic event. Treatment-related mortality (TRM) within 1 or 3 months after kidney transplantation has been seldom reported. We designed a retrospective observational cohort study using a national population-based database, which included information about all kidney recipients between 2003 and 2016. A total of 16,073 patients who underwent kidney transplantation were included. The mortality rates 1 month (early TRM) and 3 months (TRM) after transplantation were 0.5% (n = 74) and 1.0% (n = 160), respectively. Based on a multivariate analysis, older age (hazard ratio [HR] = 1.06; P < 0.001), coronary artery disease (HR = 3.02; P = 0.002), and hemodialysis compared with pre-emptive kidney transplantation (HR = 2.53; P = 0.046) were the risk factors for early TRM. Older age (HR = 1.07; P < 0.001), coronary artery disease (HR = 2.88; P < 0.001), and hemodialysis (HR = 2.35; P = 0.004) were the common independent risk factors for TRM. In contrast, cardiac arrhythmia (HR = 1.98; P = 0.027) was associated only with early TRM, and fungal infection (HR = 2.61; P < 0.001), and epoch of transplantation (HR = 0.34; P < 0.001) were the factors associated with only TRM. The identified risk factors should be considered in patient counselling, selection, and management to prevent TRM.


Subject(s)
Graft vs Host Disease/mortality , Kidney Transplantation , Adult , Age Factors , Aged , Cohort Studies , Coronary Artery Disease/complications , Female , Graft vs Host Disease/etiology , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Proportional Hazards Models , Renal Dialysis , Risk Factors , Survival Rate , Transplantation, Homologous
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