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Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5's tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA's regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.
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Neoplasias de la Boca , ARN Circular , Nexinas de Clasificación , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Ratones , Ratones Desnudos , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Femenino , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismoRESUMEN
Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5⯵m (PM2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM2.5 exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM2.5 induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM2.5 upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM2.5 and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM2.5 exposure to telomere shortening in humans.
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Contaminantes Atmosféricos , Material Particulado , Acortamiento del Telómero , Humanos , Material Particulado/toxicidad , Acortamiento del Telómero/efectos de los fármacos , Contaminantes Atmosféricos/toxicidad , Telomerasa , Línea Celular , Niño , Tamaño de la Partícula , Estudios de Cohortes , Células Epiteliales/efectos de los fármacos , Masculino , Factores de Tiempo , Exposición a Riesgos Ambientales/efectos adversos , FemeninoRESUMEN
OBJECTIVE: This study aimed to examine associations of maternal folic acid supplementation (FAS) during pregnancy with childhood overweight or obesity (OWO) or adiposity. METHODS: In a population-based cohort of 1479 children, maternal FAS during pregnancy was assessed retrospectively by questionnaires. BMI and body fat percentages were measured at a mean age of 6.4 years. Pertinent factors were accounted for in data analyses. RESULTS: Maternal FAS during pregnancy was negatively associated with OWO (adjusted odds ratio: 0.70; 95% CI: 0.50 to 0.99). There were inverse associations of maternal FAS during pregnancy with BMI z score (ß: -0.22; 95% CI: -0.39 to -0.05), whole body fat percentage (ß: -1.28; 95% CI: -2.27 to -0.30), trunk fat percentage (ß: -1.41; 95% CI: -2.78 to -0.04), and limb fat percentage (ß: -1.31; 95% CI: -2.32 to -0.30). Stratified analyses found inverse associations of FAS during pregnancy with OWO, BMI z score, and body fat percentages predominantly among children without breastfeeding and whose parents had a below-tertiary educational level. CONCLUSIONS: This study provides novel evidence that maternal FAS during pregnancy was significantly associated with a decreased risk of childhood OWO and adiposity, particularly among children with no breastfeeding and lower parental educational level.
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Índice de Masa Corporal , Suplementos Dietéticos , Ácido Fólico , Obesidad Infantil , Humanos , Femenino , Embarazo , Ácido Fólico/administración & dosificación , Niño , Estudios Retrospectivos , Masculino , Adiposidad , Sobrepeso , Adulto , Efectos Tardíos de la Exposición Prenatal , Preescolar , Fenómenos Fisiologicos Nutricionales Maternos , Lactancia MaternaRESUMEN
BACKGROUND: Anaphylaxis is an acute and serious allergic reaction. Little is known about physician adherence to anaphylaxis guidelines among patients across different age groups. OBJECTIVE: To investigate real-world physician adherence to anaphylaxis guidelines among children, adults, and older adults in emergency departments. METHODS: This study retrospectively analyzed all consecutive patients with anaphylaxis who presented to 2 emergency departments at 2 branches of the largest tertiary hospital in Taiwan, between 2001 and 2020. Patients who met the diagnostic criteria for anaphylaxis were enrolled and grouped by age: children (<18 years), adults (18-64 years), and older adults (≥65 years). RESULTS: We enrolled 771 patients with anaphylaxis (159 children, 498 adults, and 114 older adults). Intramuscular epinephrine was administered in 294 cases (38.1%). There was a significant age-group difference in the rate of intramuscular epinephrine administration (46.5% in children, 37.3% in adults, and 29.8% in older adults; P trend = .004). When stratified by severity, 14.3% of older adults with moderate reactions received intramuscular epinephrine, whereas 35.2% of adults and 55.3% of children received intramuscular epinephrine (P trend < .001), whereas such difference was not found in patients with severe reactions. Upon discharge from emergency departments, 15.3% received allergist referral (52.2% in children, 6.6% in adults, and 1.8% in older adults; P trend < .001); 12.5% received education on avoidance of triggers (18.9%, 11.4%, and 7.9%; P trend = .01), and 16.1% received education on alarm symptoms (21.4%, 15.1%, and 13.2%; P trend = .05). CONCLUSION: The real-world physician adherence to anaphylaxis guidelines remains suboptimal in emergency departments, particularly among older adults. Physician continuing education is needed to improve the gap between anaphylaxis guidelines and clinical practice.
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Anafilaxia , Médicos , Adolescente , Anciano , Niño , Humanos , Anafilaxia/diagnóstico , Anafilaxia/tratamiento farmacológico , Servicio de Urgencia en Hospital , Epinefrina/uso terapéutico , Inyecciones Intramusculares , Estudios Retrospectivos , Adulto , Recién Nacido , Preescolar , Adulto Joven , Persona de Mediana Edad , TaiwánRESUMEN
BACKGROUND: Antenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women. METHODS: Of 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009-2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment. RESULTS: Among 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69-0.83) for sepsis, 0.31 (95% CI: 0.27-0.36) for heart failure, and 11.57 (95% CI: 11.27-11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10-11.30) for sepsis and 4.45 (95% CI: 2.63-7.55) for heart failure, and 1.26 (95% CI: 1.02-1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01-3.96) for sepsis, 3.65 (95% CI: 2.14-6.22) for heart failure, and 1.81 (95% CI: 1.56-2.10) for gastrointestinal bleeding. CONCLUSIONS: This nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.
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Insuficiencia Cardíaca , Nacimiento Prematuro , Sepsis , Femenino , Embarazo , Recién Nacido , Humanos , Mujeres Embarazadas , Nacimiento Prematuro/epidemiología , Corticoesteroides/efectos adversos , Insuficiencia Cardíaca/epidemiología , Sepsis/epidemiología , Hemorragia GastrointestinalRESUMEN
Oral corticosteroids (OCS) are commonly prescribed for acute, self-limited conditions, despite studies demonstrating toxicity. Studies evaluating longitudinal OCS prescribing in the general population are scarce and do not compare use across countries. This study investigated and compared OCS prescription patterns from 2009 to 2018 in the general populations of the United States, Taiwan, and Denmark. This international population-based longitudinal cohort study used nationwide claims databases (United States: Optum Clinformatics Data Mart; de-identified; Taiwan: National Health Insurance Research Database; and Denmark: National Prescription and Patient Registries/Danish National Patient Registry) to evaluate OCS prescribing. We classified annual OCS duration as short-term (1-29 days), medium-term (30-89 days), or long-term (≥90 days). Longitudinal change in annual prevalence of OCS use and physician prescribing patterns were reported. Among 54,630,437 participants, average annual percentage of overall OCS use was 6.8% in the United States, 17.5% in Taiwan, and 2.2% in Denmark during 2009-2018. Prevalence of OCS prescribing increased at an average annual rate of 0.1%-0.17%, mainly driven by short-term prescribing to healthy adults. One-quarter to one-fifth of OCS prescribing was associated with a diagnosis of respiratory infection. Family practice and internal medicine physicians were among the highest OCS prescribers across countries and durations. Age- and sex-stratified trends mirrored unstratified trends. This study provides real-world evidence of an ongoing steady increase in OCS use in the general populations of the United States, Taiwan, and Denmark. This increase is largely driven by short-term OCS prescribing to healthy adults, a practice previously viewed as safe but recently shown to incur substantial population-level risk.
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Corticoesteroides , Adulto , Humanos , Estados Unidos/epidemiología , Prevalencia , Taiwán/epidemiología , Estudios Longitudinales , Corticoesteroides/efectos adversos , Dinamarca/epidemiologíaRESUMEN
Exposure to environmental metals has been associated with health outcomes including respiratory health. Little is known about the impact of exposure to environmental metals on lung function among young children in general population. This study aimed to investigate the associations of exposure to metals with lung function among young children in a population-based cohort. A total of 1488 children aged 5-8 years attended a follow-up visit as part of the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort. We measured urinary samples of vanadium (median: 1.21 ng/mL; interquartile range (IQR): 0.73-1.98), manganese (median: 0.23 ng/mL; IQR: 0.13-0.47), arsenic (median: 40.51 ng/mL; IQR: 21.66-70.49), nickel (median: 1.09 ng/mL; IQR: 0.31-3.60), and cadmium (median: 0.26 ng/mL; IQR: 0.11-0.43) and performed lung function tests. Urinary vanadium concentrations were inversely associated with FVC (ß coefficient for the highest quartile versus the other quartiles: -33.40, p = 0.001), FEV1 (ß: -41.31, p < 0.001), FEV1/FVC ratio (ß: -1.00, p = 0.009), PEF (ß: -92.12, p = 0.004), and FEF25-75 (ß: -82.85, p < 0.001), after adjusting for relevant confounders. Urinary manganese concentrations were inversely associated with FVC (ß: -26.60, p = 0.007), FEV1 (ß: -31.62, p = 0.001), PEF (ß: -84.86, p = 0.009), and FEF25-75 (ß: -69.21, p = 0.002). Stratification analyses found inverse associations of urinary vanadium and manganese concentrations with lung function parameters predominantly among children exposed to environmental tobacco smoke. We did not find significant associations of urinary arsenic, nickel, and cadmium concentrations with lung function parameters. In conclusion, this study adds new evidence showing inverse associations of vanadium and manganese exposure with lung function among young children in the general population. Children with environmental tobacco smoke exposure are particularly vulnerable to adverse impact of vanadium and manganese exposure on lung function.
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Arsénico , Contaminación por Humo de Tabaco , Humanos , Niño , Preescolar , Manganeso/toxicidad , Vanadio/toxicidad , Arsénico/toxicidad , Cadmio , Níquel , PulmónRESUMEN
Schoolchildren are sensitive to airborne aldehyde exposures. The knowledge regarding inhalation exposure to aldehydes and the factors influencing exposure in schoolchildren is limited. This study aimed to assess the variability and potential health risks of exposure to aldehydes (including formaldehyde) in schoolchildren. The important factors affecting personal exposure to aldehydes were also explored. Forty schoolchildren were recruited from the urban and suburban areas of Taiwan for aldehyde samplings and questionnaire surveys. Personal and indoor home samples of aldehydes were collected simultaneously during warm and cold seasons. We also identified the potential variables associated with aldehyde exposure based on the participant's responses to the questionnaires using mixed-effects models. The dominant three abundant aldehydes identified in personal exposure samples were formaldehyde (geometric mean, GM = 12.2 µg/m3), acetaldehyde (GM = 5.53 µg/m3), and hexaldehyde (GM = 8.79 µg/m3), accounting for approximately 80% of the total selected aldehydes. Higher personal exposure to aldehydes was observed during the warm season. Moreover, the within-subject variance was predominant, accounting for 66.6 to > 99.9% of the total variance in exposure. Schoolchildren had a high probability of overexposure to formaldehyde and acrolein, which resulted in an incremental lifetime cancer risk of 1.59 × 10-4 (95th percentile = 4.64 × 10-4). Season, location, household refurbishment, and indoor ventilation variables were significantly associated with personal exposure to aldehydes. The results can improve our understanding of aldehyde exposure among schoolchildren to propose mitigation strategies. These findings may be applied to further epidemiological studies.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Humanos , Niño , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Aldehídos/análisis , Formaldehído/análisis , Encuestas y CuestionariosRESUMEN
Autism spectrum disorder (ASD) is associated with a high prevalence of visual dysfunction. This study aimed to investigate the rates of amblyopia, refractive errors, and strabismus, as well as their clinical correlates in ASD. This population-based matched-cohort study used data from the Taiwan National Health Insurance Research Database. A total of 3,551 youths with ASD and 35,510 non-autistic control participants matched by age and sex were included. All the participants were followed-up until they were 18 years old. The prevalence of amblyopia, refractive errors, and strabismus was compared between the ASD and control groups. Effect modifiers, including sex, ASD subgroup, and co-diagnosis of intelligence disability, were examined. Compared to the control group, youths with ASD had a significantly increased risk of amblyopia (adjusted odds ratio [aOR] = 1.75), anisometropia (aOR = 1.66), astigmatism (aOR = 1.51), hypermetropia (aOR = 2.08), exotropia (aOR = 2.86), and esotropia (aOR = 2.63), but a comparable likelihood of myopia according to age. Males with ASD had a significantly lower likelihood of exotropia, but a higher likelihood of myopia than females with ASD. The autism subgroup had a higher OR for hypermetropia, but a lower OR for myopia than the other ASD subgroups. ASD youths with intelligence disabilities demonstrated significantly higher ORs for amblyopia, hypermetropia, and all types of strabismus and lower OR for myopia than those without intelligence disabilities. In conclusion, the rates of amblyopia, refractive errors, and strabismus were higher in youths with ASD. Ocular abnormalities in youths with ASD require a comprehensive assessment and management.
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OBJECTIVE: To investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life. DESIGN: Nationwide cohort study. SETTING: National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database, 1 January 2008 to 31 December 2019, to identify all pregnant individuals and their offspring in Taiwan. PARTICIPANTS: 1 960 545 pairs of pregnant individuals and their singleton offspring. 45 232 children were exposed and 1 915 313 were not exposed to antenatal corticosteroids. MAIN OUTCOME MEASURES: Incidence rates were estimated for overall serious infection, sepsis, pneumonia, acute gastroenteritis, pyelonephritis, meningitis or encephalitis, cellulitis or soft tissue infection, septic arthritis or osteomyelitis, and endocarditis during the first three, six, and 12 months of life in children exposed versus those not exposed to antenatal corticosteroids. Cox proportional hazards models were performed to quantify adjusted hazard ratios with 95% confidence intervals for each study outcome. RESULTS: The study cohort was 1 960 545 singleton children: 45 232 children were exposed to one course of antenatal corticosteroids and 1 915 313 children were not exposed to antenatal corticosteroids. The adjusted hazard ratios for overall serious infection, sepsis, pneumonia, and acute gastroenteritis among children exposed to antenatal corticosteroids were significantly higher than those not exposed to antenatal corticosteroids during the first six months of life (adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.47, P<0.001, for overall serious infection; 1.74, 1.16 to 2.61, P=0.01, for sepsis; 1.39, 1.17 to 1.65, P<0.001, for pneumonia; and 1.35, 1.10 to 1.65, P<0.001, for acute gastroenteritis).Similarly, the adjusted hazard ratios for overall serious infection (P<0.001), sepsis (P=0.02), pneumonia (P<0.001), and acute gastroenteritis (P<0.001) were significantly higher from birth to 12 months of life. In the sibling matched cohort, the results were comparable with those observed in the whole cohort, with a significantly increased risk of sepsis in the first six (P=0.01) and 12 (P=0.04) months of life. CONCLUSIONS: This nationwide cohort study found that children exposed to one course of antenatal corticosteroids were significantly more likely to have an increased risk of serious infection during the first 12 months of life. These findings suggest that before starting treatment, the long term risks of rare but serious infection associated with antenatal corticosteroids should be carefully weighed against the benefits in the perinatal period.
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Corticoesteroides , Nacimiento Prematuro , Humanos , Embarazo , Niño , Femenino , Estudios de Cohortes , Corticoesteroides/efectos adversos , Taiwán/epidemiologíaRESUMEN
Bronchiolitis is the most common seasonal viral respiratory disorder in infants. However, risk factors for the development of bronchiolitis, particularly during pregnancy, remain unclear. Methods: A questionnaire was administered to the parents of the hospitalized infants with acute bronchiolitis to obtain information regarding patients' medical, family, and prenatal exposure history. Logistic regression with adjustment was performed to evaluate risk factors associated with bronchiolitis in the infants. Results: Among the enrolled patients, 55 (36.7%) were diagnosed as having bronchiolitis, and the majority (89%) of the patients had moderate-to-severe bronchiolitis. The bronchiolitis group had lower C-reactive protein levels than did the control group. Fewer patients in the bronchiolitis group developed fever. However, hospital stays were longer in the bronchiolitis group than in the control group. Respiratory syncytial virus was the most detected virus (23/26, 88.6%) in the bronchiolitis group. Male sex (odds ratio [OR], 5.71; 95% confidence interval [CI], 2.02-16.12; P < 0.001), antibiotic usage during pregnancy (OR, 27.2; 95% CI, 1.12-660.84; P = 0.04), and viral infection (OR, 49.3; 95% CI, 9.01-270.26; P < 0.001) during the postnatal period were significantly associated with hospitalization for acute bronchiolitis in the infants. By contrast, pet exposure during the perinatal period was significantly and negatively associated with acute bronchiolitis (OR = 0.21, 95% CI = 0.07-0.69, P < 0.01). Conclusion: Environmental exposures during pregnancy may affect respiratory health in offspring, and effective strategies should be developed to prevent bronchiolitis in early life.
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Mixed cryoglobulinemia (MC) is a hepatitis C virus (HCV)-related extrahepatic manifestation that is characterized by the abnormal presence of immune complexes (ICs). This may be due to the reduced uptake and clearance of ICs. The C-type lectin member 18A (CLEC18A) is a secretory protein that is expressed abundantly in hepatocytes. We previously observed that CLEC18A increased significantly in the phagocytes and sera of patients with HCV, particularly those with MC. Herein, we explored the biological functions of CLEC18A in the MC syndrome development of patients with HCV by using an in vitro cell-based assay with quantitative reverse transcription-PCR, immunoblotting, immunofluorescence, flow cytometry, and enzyme-linked immunosorbent assays. HCV infection or Toll-like receptor 3/7/8 activation could induce CLEC18A expression in Huh7.5 cells. Upregulated CLEC18A interacts with Rab5 and Rab7 and enhances type I/III interferon production to inhibit HCV replication in hepatocytes. However, overexpressed CLEC18A suppressed phagocytic activity in phagocytes. Significantly decreased levels of the Fc gamma receptor (FcγR) IIA were found in the neutrophils of HCV patients, particularly in those with MC (P < 0.005). We demonstrated that CLEC18A could inhibit FcγRIIA expression in a dose-dependent manner through the production of NOX-2-dependent reactive oxygen species to impair the uptake of ICs. Additionally, CLEC18A suppresses the Rab7 expression that is induced by starvation. Overexpressed CLEC18A does not affect autophagosome formation but does reduce the recruitment of Rab7 to autophagosomes, thereby retarding the maturation of autophagosomes and affecting autophagosome-lysosome fusion. We offer a novel molecular machinery with which to understand the association of HCV infection with autoimmunity and propose that CLEC18A may act as a candidate biomarker for HCV-associated MC. IMPORTANCE During infection, the host immune system produces cellular factors to protect against pathogen invasion. However, when the immune response overreacts and there is dysregulated cytokine homeostasis, autoimmunity occurs following an infection. We identified a cellular factor that is involved in HCV-related extrahepatic manifestation, namely, CLEC18A, which is expressed abundantly in hepatocytes and phagocytes. It inhibits HCV replication in hepatocytes by interacting with Rab5/7 and enhancing type I/III IFN expression. However, overexpressed CLEC18A inhibited FcγRIIA expression in phagocytes to impair phagocytosis. Furthermore, the interaction between CLEC18A and Rab5/7 may reduce the recruitment of Rab7 to autophagosomes and thereby retard autophagosome maturation and cause immune complex accumulation. A decreasing trend in CLEC18A levels that was accompanied by reduced HCV RNA titers and diminished cryoglobulin was observed in the sera of HCV-MC patients after direct-acting antiviral therapy. CLEC18A may be used for the evaluation of anti-HCV therapeutic drug effects and could be a potential predisposing factor for the development of MC syndrome.
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Hepatitis C Crónica , Hepatitis C , Humanos , Receptores de IgG , Antivirales/farmacología , Autofagosomas , Hepacivirus/genética , Fagocitosis , Lisosomas , Lectinas Tipo C/genéticaRESUMEN
(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. This study aimed to explore the association of SCFAs with the severity of NAFLD in T2D patients. (2) Methods: We employed echography to examine the severity of hepatic steatosis. The serum levels of nine SCFAs, namely, formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured using gas chromatography mass spectrometry. (3) Results: A total of 259 T2D patients was enrolled in this cross-sectional study. Of these participants, 117 with moderate to severe NAFLD had lower levels of formate, isobutyrate, and methylbutyrate than the 142 without NAFLD or with mild NAFLD. Lower circulating levels of isobutyrate and methylbutyrate were associated with an increased severity of NAFLD. A relationship between NAFLD severity and circulating isobutyrate and methylbutyrate levels was found independently of a glycated hemoglobin (HbA1C) level of 7.0%. (4) Conclusion: Circulating levels of isobutyrate and methylbutyrate were significantly and negatively correlated with NAFLD severity in the enrolled T2D patients. SCFAs may be related to NAFLD severity in T2D patients.
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Diabetes Mellitus Tipo 2 , Ácidos Grasos Volátiles , Hígado Graso , Enfermedad del Hígado Graso no Alcohólico , Humanos , Ácidos Grasos Volátiles/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Diabetes Mellitus Tipo 2/sangre , Ultrasonografía , Hígado Graso/diagnóstico por imagen , Isobutiratos/sangre , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
This cohort study examines the association of the use of leukotriene-receptor antagonists during pregnancy with the risk of neuropsychiatric events in offspring.
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Antagonistas de Leucotrieno , Leucotrienos , Femenino , Embarazo , Humanos , Antagonistas de Leucotrieno/uso terapéuticoRESUMEN
Platelet hyper-reactivity and neutrophil extracellular trap (NET) formation contribute to the development of thromboembolic diseases for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the pathophysiological effects of SARS-CoV-2 surface protein components and the viral double-stranded RNA (dsRNA) on platelet aggregation and NET formation. Traditional Chinese medicine (TCM) with anti-viral effects was also delineated. The treatment of human washed platelets with SARS-CoV-2 spike protein S1 or the ectodomain S1 + S2 regions neither caused platelet aggregation nor enhanced agonists-stimulated platelet aggregation. Moreover, NET formation can be induced by polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of viral dsRNA, but not by the pseudovirus composed of SARS-CoV-2 spike, envelope, and membrane proteins. To search for TCM with anti-NET activity, the plant Melastoma malabathricum L. which has anticoagulant activity was partially purified by fractionation. One of the fractions inhibited poly(I:C)-induced NET formation in a dose-dependent manner. This study implicates that SARS-CoV-2 structural proteins alone are not sufficient to promote NET and platelet activation. Instead, dsRNA formed during viral replication stimulates NET formation. This study also sheds new insight into using the active components of Melastoma malabathricum L. with anti-NET activity in the battle of thromboembolic diseases associated with SARS-CoV-2 infection.
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Both greenness and air pollution have widely been linked with asthma. However, the potential mechanism has rarely been investigated. This study aimed to identify the association between residential greenness and air pollution (fine particulate matter [PM2.5]; nitrogen dioxide [NO2]; ozone [O3]) with nasal microbiota among asthmatic children during the recovery phase. The normalized difference vegetation index was used to assess the extent of residential greenness. Spatiotemporal air pollution variation was estimated using an integrated hybrid kriging-LUR with the XG-Boost algorithm. These exposures were measured in 250-m intervals for four incremental buffer ranges. Nasal microbiota was collected from 47 children during the recovery phase. A generalized additive model controlled for various covariates was applied to evaluate the exposure-outcome association. The lag-time effect of greenness and air pollution related to the nasal microbiota also was examined. A significant negative association was observed between short-term exposure to air pollution and nasal bacterial diversity, as a one-unit increment in PM2.5 or O3 significantly decreased the observed species (PM2.5: -0.59, 95%CI -1.13, -0.05 and O3: -0.93, 95%CI -1.54, -0.32) and species richness (PM2.5: -0.64, 95%CI -1.25, -0.02 and O3: -0.68, 95%CI -1.43, -0.07). Considering the lag-time effect, we found a significant positive association between greenness and both the observed species and species richness. In addition, we identified a significant negative association for all pollutants with the observed species richness. These findings add to the evidence base of the links between nasal microbiota and air pollution and greenness. This study establishes a foundation for future studies of how environmental exposure plays a role in nasal microbiota, which in turn may affect the development of asthma.
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Contaminantes Atmosféricos , Contaminación del Aire , Asma , Humanos , Niño , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Asma/epidemiología , Material Particulado/análisis , Exposición a Riesgos Ambientales/análisis , Dióxido de Nitrógeno/análisisRESUMEN
BACKGROUND: Studies on insomnia in patients with ischemic stroke, particularly in the acute phase, are limited. The proportion of patients with sleep disturbance during the acute stroke period who are likely to develop insomnia in subacute and chronic stages of stroke is unknown. This study aimed to investigate the risk factors for sleep disturbance and the clinical course of the disease in patients with acute ischemic stroke. METHODS: This prospective observational study included patients diagnosed with ischemic stroke between July 1, 2020, and October 31, 2021. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) for insomnia and the eight-item Athens Insomnia Scale (CAIS-8) were used to diagnose insomnia. Beck Depression Inventory (BDI) was applied to evaluate the mood of patients. Patient reported their sleeping conditions, before stroke onset and during the acute (within 7 days) and chronic (3 months after presentation) stroke periods. RESULTS: In total, 195 patients with ischemic stroke were included in this study. Of these, 34.3% (67), 37.4% (73), and 29.7% (58) presented with sleep disturbance before stroke onset and during the acute and chronic stroke periods, respectively. Of the 128 patients without insomnia before stroke onset, 15.6% (20/128) presented with insomnia symptoms 3 months after stroke onset. Moreover, 13 (12.7%) of the 102 patients without sleep disturbance during the acute stroke period developed insomnia 3 months after stroke onset. Of the 67 patients with insomnia before stroke onset 29 (43.3%) did not develop the condition 3 months after stroke onset. A higher risk of sleep disturbance was associated with atrial fibrillation, hypertension, and mood disturbance in the acute stroke period, and a higher risk of insomnia was associated with low education and mood disturbance in the chronic stroke period. CONCLUSION: The prevalence rates of sleep disturbance before and during the acute and chronic stroke periods were 34.3%, 37.4%, and 29.7%, respectively. The incidence of stroke-related insomnia was 15.6%. Patients with insomnia before stroke may recover after the stroke. Atrial fibrillation, hypertension, and mood disturbance were associated with a higher risk of sleep disturbance in the acute stroke period, whereas low education and mood disturbance were associated with insomnia in the chronic stroke period.
Asunto(s)
Fibrilación Atrial , Hipertensión , Accidente Cerebrovascular Isquémico , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Accidente Cerebrovascular , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , SueñoRESUMEN
Whether parental psychiatric disorders are associated with autism spectrum disorder (ASD) in offspring has remained inconclusive. We examined the associations of parental psychiatric disorders with ASD in offspring. This population-based case-control study used Taiwan's National Health Insurance Research Database to identify a cohort of children born from 2004 to 2017 and their parents. A total of 24,279 children with ASD (diagnostic ICD-9-CM code: 299.x or ICD-10 code F84.x) and 97,715 matched controls were included. Parental psychiatric disorders, including depressive disorders, bipolar spectrum disorders, anxiety disorders, obsessive-compulsive disorder, schizophrenia, substance use disorders, autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), and adjustment disorders were identified. Conditional logistic regressions with covariate adjustment were performed. The results suggest that parental diagnosis with any of the psychiatric disorders is associated with ASD in offspring (adjusted odds ratio [AOR] = 1.45, 95%CI: 1.40-1.51 for mothers; and AOR = 1.12, 95%CI: 1.08-1.17 for fathers). ASD in offspring was associated with schizophrenia, depressive disorders, obsessive-compulsive disorder, adjustment disorders, ADHD and ASD in both parents. The relationship between parental psychiatric disorders and the timing of the child's birth and ASD diagnosis varied across the different psychiatric disorders. The present study provides supportive evidence that parental psychiatric disorders are associated with autistic children. Furthermore, because the associations between parental psychiatric disorders and the timing of child's birth and ASD diagnosis varied across psychiatric disorders, the observed relationships may be affected by both genetic and environmental factors. Future studies are needed to disentangle the potential influence of genetic and environmental factors on the observed associations.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Niño , Femenino , Humanos , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/complicaciones , Estudios de Casos y Controles , Padres/psicología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Madres/psicologíaRESUMEN
Background: Osteoporosis is associated with many serious health conditions that have a severely negative impact on quality of life, as well as higher rates of morbidity and mortality. Due to the aging society and low birth rate in Taiwan, an increasing number of people are living alone. This longitudinal study was aimed to assess the relationship between living alone and calcaneus ultrasound T-score in a large cohort in Taiwan. Methods: A total of 118,853 participants enrolled in the Taiwan Biobank since 2008 to 2016, who had complete calcaneus ultrasound examinations were collected in the baseline study. Of these participants, 26,850 received complete follow-up measurements after a median of 4 years. The T-score (g/cm2) of the calcaneus in the non-dominant foot was measured using ultrasound. Changes in the calcaneus ultrasound T-score (ΔT-score) were calculated as follow-up T-score minus baseline T-score. We analyzed these data in 2022. We used multivariable linear regression analysis to investigate correlation between living alone with baseline T-score and ΔT-score. We also carried out separate analyses for men and women. Results: The mean age of the participants was 49.89 ± 10.95 years, and multivariable analysis showed that living alone was significantly correlated to low baseline T-score in whole cohort (ß = -0.040; p = 0.012) and women (ß = -0.055; p = 0.023). Furthermore, living alone (coefficient ß = -0.049; p = 0.048) was significantly correlated to a low ΔT-score after 4 years of follow-up. Conclusion: In this large population-based longitudinal study, living alone may be related to low baseline calcaneus ultrasound T-score and ΔT-score. Adopting long-term community-based care policies to increase the activity of people living alone may help to prevent osteoporosis and decrease the risk of fractures in Taiwan.