Background Recent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic ...dermatitis (AD) risk remains poorly understood. Objective We investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species. Methods Two general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases COCOA) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children PSKC) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11β-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured. Results In COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1 year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 95% CI, 1.02-1.69; hazard ratio for anxiety, 1.41 95% CI, 1.06-1.89) and PSKC (odds ratio for distress, 1.85 95% CI, 1.06-3.25). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD ( P < .001 in both). Prenatal distress decreased placental glutathione to glutathione disulfide ratios ( P = .037) and, especially in those who later had AD, decreased placental 11β-hydroxysteroid dehydrogenase type 2 levels ( P = .010) and increased IgE levels at 1 year of age ( P = .005). Conclusion Prenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.
Most individuals with Down Syndrome (DS) show an early-onset of Alzheimer's disease (AD), which potentially results from the presence of an extra copy of a segment of chromosome 21. Located on ...chromosome 21 are the genes that encode β-amyloid (Aβ) precursor protein (APP ), a key protein involved in the pathogenesis of AD, and dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A (DYRK1A ), a proline-directed protein kinase that plays a critical role in neurodevelopment. Here, we describe a potential mechanism for the regulation of AD pathology in DS brains by DYRK1A-mediated phosphorylation of APP. We show that APP is phosphorylated at Thr668 by DYRK1A in vitro and in mammalian cells. The amounts of phospho-APP and Aβ are increased in the brains of transgenic mice that over-express the human DYRK1A protein. Furthermore, we show that the amounts of phospho-APP as well as those of APP and DYRK1A are elevated in human DS brains. Taken together, these results reveal a potential regulatory link between APP and DYRK1A in DS brains, and suggest that the over-expression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.
Circulating tumor DNA (ctDNA) has emerged as a candidate biomarker for cancer screening. However, studies on the usefulness of ctDNA for postoperative recurrence monitoring are limited. The present ...study monitored ctDNA in postoperative blood by employing cancer-specific rearrangements. Personalized cancer-specific rearrangements in 25 gastric cancers were analyzed by whole-genome sequencing (WGS) and were employed for ctDNA monitoring with blood up to 12 months after surgery. Personalized cancer-specific rearrangements were identified in 19 samples. The median lead time, which is the median duration between a positive ctDNA detection and recurrence, was 4.05 months. The presence of postoperative ctDNA prior to clinical recurrence was significantly correlated with cancer recurrence within 12 months of surgery (P = 0.029); in contrast, no correlation was found between cancer recurrence and the presence of preoperative ctDNA, suggesting the clinical usefulness of postoperative ctDNA monitoring for cancer recurrence in gastric cancer patients. However, the clinical application of ctDNA can be limited by the presence of ctDNA non-shedders (42.1%, 8/19) and by inconsistent postoperative ctDNA positivity.
Bispectral index (BIS), a useful marker of anaesthetic depth, is calculated by a statistical multivariate model using nonlinear functions of electroencephalography-based subparameters. However, only ...a portion of the proprietary algorithm has been identified. We investigated the BIS algorithm using clinical big data and machine learning techniques. Retrospective data from 5,427 patients who underwent BIS monitoring during general anaesthesia were used, of which 80% and 20% were used as training datasets and test datasets, respectively. A histogram of data points was plotted to define five BIS ranges representing the depth of anaesthesia. Decision tree analysis was performed to determine the electroencephalography subparameters and their thresholds for classifying five BIS ranges. Random sample consensus regression analyses were performed using the subparameters to derive multiple linear regression models of BIS calculation in five BIS ranges. The performance of the decision tree and regression models was externally validated with positive predictive value and median absolute error, respectively. A four-level depth decision tree was built with four subparameters such as burst suppression ratio, power of electromyogram, 95% spectral edge frequency, and relative beta ratio. Positive predictive values were 100%, 80%, 80%, 85% and 89% in the order of increasing BIS in the five BIS ranges. The average of median absolute errors of regression models was 4.1 as BIS value. A data driven BIS calculation algorithm using multiple electroencephalography subparameters with different weights depending on BIS ranges has been proposed. The results may help the anaesthesiologists interpret the erroneous BIS values observed during clinical practice.
ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ...ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD
)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.
To achieve high performance photoelectrochemical CO sub(2) reduction, a polypyrrole-coated p-ZnTe electrode (PPy/ZnTe) was fabricated as a new photocathode material and its catalytic activities were ...investigated. The PPy deposited on the p-ZnTe electrode improved the photoelectrochemical CO sub(2) reduction activity as a surface modifying catalyst. Under the irradiation of visible light, the PPy/ZnTe showed a prominent performance with a 51.0% of Faradaic efficiency at -0.2 V (vs.RHE) without any significant overpotential loss. The ultraviolet photoelectron spectroscopy (UPS) and electrochemical impedance spectroscopy (EIS) implied that the enhanced catalytic performances were primarily attributed to the enhanced conversion efficiency of photoenergy on the PPy/ZnTe. It was suggested that the PPy/ZnTe electrode improved the generation of photo-induced electron-hole pairs, and the different work functions of ZnTe and PPy introduced an electron pathway from ZnTe to PPy and then to the reactants.
In this work, we introduce a low cost, room-temperature and atmospheric pressure based chemical method to produce highly transparent, conductive, and flexible nano-mesh structured electrodes using Ag ...nanocrystals (NCs). Sequential treatments of ligand exchange and reduction processes were developed to engineer the optoelectronic properties of Ag NC thin films. Combinatorial analysis indicates that the origin of the relatively low conductivity comes from the non-metallic compounds that are introduced during ligand exchange. The reduction process successfully removed these non-metallic compounds, yielding structurally uniform, optically more transparent, dispersive, and electrically more conductive thin films. We optimized the design of Ag NC thin film mesh structures, and achieved low sheet resistance (9.12 Ω □-1), high optical transmittance (94.7%), and the highest figure of merit (FOM) of 6.37 × 10-2. Solution processed flexible transparent heaters, touch pads, and wearable sensors are demonstrated, emphasizing the potential applications of Ag NC transparent electrodes in multifunctional sensors and devices.
Chronic exposure to bile acid in the liver due to impaired bile flow induces cholestatic liver disease, resulting in hepatotoxicity and liver fibrosis. Sestrin2, a highly conserved, stress-inducible ...protein, has been implicated in cellular responses to multiple stress conditions and the maintenance of cellular homeostasis. However, its role in cholestatic liver injury is not fully understood. In this study, we investigated the role of hepatic Sestrin2 in cholestatic liver injury and its underlying mechanisms using in vivo and in vitro approaches. Hepatic Sestrin2 expression was upregulated by activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-β (C/EBP-β) after treatment with bile acids and correlated with endoplasmic reticulum (ER) stress responses. Bile-duct ligation (BDL)-induced hepatocellular apoptosis and liver fibrosis were exacerbated in Sestrin2-knockout (Sesn2
) mice. Moreover, Sestrin2 deficiency enhanced cholestasis-induced hepatic ER stress, whereas Sestrin2 overexpression ameliorated bile acid-induced ER stress. Notably, the mammalian target of rapamycin (mTOR) inhibitor rapamycin and the AMP-activated protein kinase (AMPK) activator AICAR reversed bile acid-induced ER stress in Sestrin2-deficient cells. Furthermore, Sestrin2 deficiency promoted cholestasis-induced hepatic pyroptosis by activating NLRP3 inflammasomes. Thus, our study provides evidence for the biological significance of Sestrin2 and its relationship with cholestatic liver injury, suggesting the potential role of Sestrin2 in regulating ER stress and inflammasome activation during cholestatic liver injury.
This study aimed to evaluate factors that predict lymph node metastasis (LNM) in papillary thyroid cancer (PTC). This retrospective cross-sectional study compared the demographic, clinical, and ...ultrasonographic findings of patients with PTC with and without LNM. Subgroup analysis was conducted for micro-PTCs (<1 cm). Among total (n = 512; mean age, 47.3 ± 12.7 years) and micro-PTC patients (n = 312), 35.7% and 19.6% had LNM, respectively. Younger age, male sex, tumor size, bilaterality, and suspicious ultrasound features of the tumor were associated with LNM. In multiple logistic regression analysis, among all patients, age, tumor size, and extrathyroidal extension were independent risk factors for LNM (all p<0.05). In the micro-PTC subgroup, age, extrathyroidal extension, bilaterality of tumor, and presence of autoimmune thyroid disease were independent risk and protective factors for LNM (all p<0.05). In the receiver operating characteristic analysis, the accuracy of the multivariable logistic regression model for predicting LNM among all patients and micro-PTC was acceptable (area under the curve = 0.729 and 0.733, respectively). Age, sex, tumor size, and extrathyroidal extension can assist in predicting LNM in PTC patients. Additionally, the bilaterality of tumors and presence of autoimmune thyroid disease can assist in predicting LNM in micro-PTCs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since the 1970s, the public has been advised to limit egg consumption even though there is little evidence of any harmful effect of eggs on blood cholesterol. The purpose of this cross-sectional and ...prospective study was to evaluate the potential association between egg consumption and metabolic syndrome (MetS) and MetS components in adults ≥ 40 years in KoGES_Yangpyeong. Yangpyeong is a rural area in South Korea. A total of 2,887 subjects (men 1,115, women 1,772) were recruited from 2005 to 2009, based on a physical examination and questionnaires administered using standardized protocol. After excluding subjects who had MetS at baseline, 1,663 subjects (675 men, 958 women) were followed for 3.20 years (range: 0.34-8.70). During the follow-up period, MetS occurred in 289 subjects. More than 3 eggs per week was significantly associated with decreased risk of MetS in both men (RR = 0.46, 95% CI, 0.26-0.82, P for trend = 0.1093) and women (RR = 0.54, 95% CI, 0.31-0.93, P for trend 0.0325) compared to non-users. There was a cross-sectional inverse relationship between egg consumption and abdominal obesity in men and women. Also, prospectively, higher egg consumption in men was associated with a decreased risk of high fasting blood glucose (RR = 0.39, 95% CI, 0.22-0.67, P for trend = 0.0042) and high triglycerides (RR = 0.42, 95% CI, 0.22-0.80, P for trend = 0.1080). In conclusion, our findings suggest that higher egg consumption may reduce the risk of MetS both in men and women, and the risk of high fasting blood glucose and high triglycerides in men. Current guidelines regarding egg consumption may need to be re-visited for healthy middle-aged and elderly people.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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