Maternal folic acid supplementation during pregnancy in association with childhood overweight or obesity.

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.

Anti-inflammatory constituents from a sea anemone-derived fungus Arthrinium arundinis MA30.

In this study, preliminary field-sampling of bioactive fungal strains and bioassay-guided selection were conducted. A number of fungal strains were isolated from sea anemones along the northeastern coast of Badouzi, Keelung, Taiwan. Among them, Arthrinium arundinis MA30 showed significant anti-inflammatory activity and was thus selected for further chemical investigation. After a series of purification and isolation using different chromatographic techniques on the fermented products of A. arundinis MA30, thirty-one compounds were identified, five of which were previously unreported, including arthrinoic acid, hexylaconitic anhydride methyl ester, (3S,8R)-8-hydroxy-3-carboxy-2-methylenenonanoic acid, and arthripenoids G and H. These compounds were subjected to comprehensive spectroscopic data analysis. Of all the isolates, 1,3,5,6-tetrahydroxy-8-methylxanthone and arthripenoid C demonstrated the most distinctive inhibitory activities against nitric oxide production in mouse microglial BV-2 cells, with their respective inhibitory rates being 71% and 81% at 10 µM concentration, and their respective IC50 values were further determined to be 5.3 ± 0.6 and 1.6 ± 0.4 µM. These compounds showed no significant cytotoxicity, and curcumin was used as a positive control in this study.

Chemical constituents from the medicinal herb-derived fungus Chaetomium globosum Km1226.

BACKGROUND: Endophytic fungi have proven to be a rich source of novel natural products with a wide-array of biological activities and higher levels of structural diversity. RESULTS: Chemical investigation on the liquid- and solid-state fermented products of Chaetomium globosum Km1226 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-14. Their structures were determined by spectroscopic analysis as three previously undescribed C13-polyketides, namely aureonitol C (1), mollipilins G (2), and H (3), along with eleven known compounds 4-14. Among these, mollipilin A (5) exhibited significant nitric oxide production inhibitory activity in LPS-induced BV-2 microglial cells with an IC50 value of 0.7 ± 0.1 µM, and chaetoglobosin D (10) displayed potent anti-angiogenesis property in human endothelial progenitor cells (EPCs) with an IC50 value of 0.8 ± 0.3 µM. CONCLUSIONS: Three previously unreported compounds 1-3 were isolated and identified. Mollipilin A (5) and chaetoglobosin D (10) could possibly be developed as anti-inflammatory and anti-angiogenic lead drugs, respectively.

Prevalence, associated factors, and impact of adolescent asthma in Taiwan: Global Asthma Network phase I survey.

Background: The prevalence of asthma in Taiwan was increasing in the past 30 years, causing a great impact on adolescent health. This study aimed to investigate the current prevalence, impact, and associated factors of asthma in Taiwanese adolescents. Material and methods: Parents or guardians provided passive consent at home prior to the survey. Adolescents aged 13-14 years completed a questionnaire survey in 2017 in Taipei, Taiwan. The prevalence, impact, and associated factors of asthma were analyzed. We also compared the asthma prevalence with the prevalence in 1995 and 2001. Results: We analyzed 3474 validated questionnaires. The prevalence of physician-diagnosed asthma was 12.4%. The prevalence of current wheezing was 9.2% in 2017, which was 5.2% in 1995 and 7.0% in 2001. 3.3% of 13-14-year-old adolescents had severe asthma symptoms. Asthma significantly impacted the lives of adolescents. Of the students with asthma, 10.9% had school absenteeism, 16.5% urgently needed to see a doctor, 9.5% went to the emergency department, and 3.5% were admitted to hospitals within the preceding 12 months. The associated factors for physician-diagnosed asthma in Taiwanese adolescents were male (prevalence ratio [PR], 1.38; 95% confidence interval [CI], 1.05-1.83; p = 0.02), maternal history of asthma (PR, 2.61; 95% CI, 1.69-4.02; p < 0.01), and recent paracetamol use at least once per month (PR, 2.60; 95% CI, 1.24-5.42; p = 0.01). The associated factors for school absenteeism were nocturnal cough (PR, 1.99; 95% CI, 1.16-3.41; p = 0.01), current wheezing (PR, 7.52; 95% CI, 4.39-12.9; p < 0.01), and recent paracetamol use (at least once per month, PR, 3.16; 95% CI, 1.10-9.06; p = 0.03; at least once per year, PR, 2.19; 95% CI, 1.25-3.83; p < 0.01). Conclusions: The prevalence of physician-diagnosed asthma was 12.4%. Asthma substantially impacted the lives of adolescents. Reducing nocturnal cough, wheezing frequency, and paracetamol usage might help decrease school absenteeism.

Rising prevalence of food allergies in Taiwan: An epidemiological study.

BACKGROUND: Food allergies are becoming more prevalent globally. The purpose of this study was to investigate the epidemiology of food allergies in Taiwan. METHODS: In 2017, a food allergy questionnaire was administered to 6-7-year-old children, 13-14-year-old adolescents, and their parents in Taipei. The results were compared to those from a previous survey conducted in 2004. RESULTS: A total of 16,200 questionnaires were completed, revealing a rise in the prevalence of food allergies from 7.7% to 10.4% in the pediatric group and from 6.4% to 12.5% in the adult group. Peanut allergies also increased to 1.1%. Shrimp and crabs were the most common allergens, with urticaria being the most common symptom. Shortness of breath or wheezing occurred in 10% of individuals, while 2.1% experienced syncope or shock, and 0.1% were admitted to an intensive care unit. Personal history of allergic rhinitis and atopic dermatitis, as well as family histories of food allergies, were risk factors for food allergy in 6-7-year-old children. In the 13-14-year-old group, personal history of asthma, allergic rhinitis, or atopic dermatitis, recent use of acetaminophen, and living with dogs were risk factors. Females, personal histories of asthma, allergic rhinitis, atopic dermatitis, and moist and damp at home were risk factors in adults. Breastfeeding was a protective factor in 6-7-year-old children. CONCLUSION: The increasing prevalence of food allergies, including peanut allergies, in Taiwan warrants attention from physicians to provide appropriate care and education to patients with food allergies. The protective effect of breastfeeding against food allergies shall be emphasized.

Chemical Constituents and Bioactive Principles from the Mexican Truffle and Fermented Products of the Derived Fungus Ustilago maydis MZ496986.

To look in-depth into the traditional Mexican truffle, this study investigated the phytochemical and pharmacological properties of field-collected corn galls and the fermentate of its pathogen Ustilago maydis MZ496986. Here, we established the chemical profiles of both materials via the gradient HPLC-UV method and successfully identified six previously unreported chemical entities, ustilagols A-F (1-6), and 17 known components. Compounds 3, 5, and 9 exhibited potent nitric oxide production inhibitory activities in murine brain microglial BV-2 cells (IC50 = 6.7 ± 0.5, 5.8 ± 0.9, and 3.9 ± 0.1 µM) without cytotoxic effects. DIMBOA (9) also attenuates lipopolysaccharide (LPS)-stimulated NF-κB activation in RAW 264.7 macrophages (IC50 = 58.1 ± 7.2 µM). Ustilagol G (7) showed potent antiplatelet aggregation in U46619-stimulated human platelets (IC50 = 16.5 ± 5.3 µM). These findings highlighted the potential of corn galls and U. maydis MZ496986 fermentate as functional foods for improving inflammation-related discomforts and vascular obstruction.

Anti-Epstein-Barr Viral Agents from the Medicinal Herb-Derived Fungus Alternaria alstroemeriae Km2286.

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D (1-4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1-6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 µM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1-4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 µM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.

Radiomics nomogram for prediction disease-free survival and adjuvant chemotherapy benefits in patients with resected stage I lung adenocarcinoma.

BACKGROUND: Robust imaging biomarkers are needed for risk stratification in stage I lung adenocarcinoma patients in order to select optimal treatment regimen. We aimed to construct and validate a radiomics nomogram for predicting the disease-free survival (DFS) of patients with resected stage I lung adenocarcinoma, and further identifying candidates benefit from adjuvant chemotherapy (ACT). METHODS: Using radiomics approach, we analyzed 554 patients' computed tomography (CT) images from three multicenter cohorts. Prognostic radiomics features were extracted from computed tomography (CT) images and selected using least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for DFS stratification. The biological basis of radiomics was explored in the Radiogenomics dataset (n=79) by gene set enrichment analysis (GSEA). Then a nomogram that integrated the signature with these significant clinicopathologic factors in the multivariate analysis were constructed in the training cohort (n=238), and its prognostic accuracy was evaluated in the validation cohort (n=237). Finally, the predictive value of nomogram for ACT benefits was assessed. RESULTS: The radiomics signature with higher score was significantly associated with worse DFS in both the training and validation cohorts (P<0.001). The GSEA presented that the signature was highly correlated to characteristic metabolic process and immune system during cancer progression. Multivariable analysis revealed that age (P=0.031), pathologic TNM stage (P=0.043), histologic subtype (P=0.010) and the signature (P<0.001) were independently associated with patients' DFS. The integrated radiomics nomogram showed good discrimination performance, as well as good calibration and clinical utility, for DFS prediction in the validation cohort. We further found that the patients with high points (point ≥8.788) defined by the radiomics nomogram obtained a significant favorable response to ACT (P=0.04) while patients with low points (point <8.788) showed no survival difference (P=0.7). CONCLUSIONS: The radiomics nomogram could be used for prognostic prediction and ACT benefits identification for patient with resected stage I lung adenocarcinoma.

Exercise-induced bronchoconstriction in children with asthma: An observational cohort study.

BACKGROUND/PURPOSE: The diagnosis of exercise-induced bronchoconstriction (EIB) was established by changes in lung function after exercise challenge. The prevalence of EIB and factors related to EIB were not fully described in children with asthma. The aim of this study was to investigate the prevalence and predictors of EIB in children with asthma. METHODS: A total of 149 children with physician-diagnosed asthma above 5 years of age underwent standardized treadmill exercise challenge for EIB and methacholine challenge for airway hyper-responsiveness from October 2015 to December 2016. RESULTS: EIB presented in 52.5% of children with asthma. Compared with children without EIB, there were more patients with atopic dermatitis in children with EIB (p = 0.038). Allergic to Dermatohagoides pteronyssinus and Dermatophagoides farinae were also found more in children with EIB (p = 0.045 and 0.048 respectively). Maximal decrease in forced expiratory volume in 1 s (FEV1) were highest in patients who were most sensitive to methacholine provocation (provocation concentration causing 20% fall in FEV1 [PC20] ≤ 1 mg/mL). Patients, who were more sensitive to methacholine challenge (with lower PC20 levels), develop EIB with more decline in FEV1 after exercise challenge (p = 0.038). Among patients with EIB, airflow limitation development in patient with methacholine-induced airway hyper-responsiveness was more abrupt and severe compared with patients without airway hyper-responsiveness (p = 0.045 and 0.033 respectively). CONCLUSION: EIB presented in 52.5% of children with asthma. The more severe methacholine-induced hyper-responsiveness, the higher prevalence of EIB as well as the severity.

Prevalence of airway hyperresponsiveness and its seasonal variation in children with asthma.

BACKGROUND: Airway hyperresponsiveness (AHR) is a key feature of asthma and can be detected using various bronchoprovocation tests. In pediatric populations, the percentage of a positive methacholine challenge test (MCCTs) in children with asthma varies among studies, and some have reported seasonal variability. However, these studies have mostly been conducted in temperate regions. This study evaluated the prevalence of AHR to methacholine and its seasonal variation in asthmatic children in Taiwan, a subtropical country. METHODS: A total of 276 children with asthma and their MCCT results were retrospectively reviewed. All were diagnosed with asthma and received asthma controllers regularly. They were assigned to four season groups depending in which season MCCTs were administered, with seasons categorized by the Central Weather Bureau of Taiwan. Subgroup analyses, including for sex, age, and atopy level, were compared for seasonal difference. RESULTS: The prevalence of methacholine hyperresponsiveness was 70.7% (n = 195), and the children who were younger and had higher total serum IgE were more sensitive to methacholine (p = 0.019 and p < 0.005, respectively). No significant difference in AHR prevalence among seasons was observed (p = 0.480). The percentage of borderline, mild, and moderate severity of MCCT results was almost equally distributed among the seasons. In subgroup analysis, the children with a higher IgE level (≥75th percentile of all data) had a higher proportion of positive MCCTs in summer (88.6%, p = 0.016). CONCLUSION: In total, 70% of the children with asthma in Taiwan had AHR to methacholine, which varied among seasons. Children with a higher total serum IgE level may be more seasonally dependent, particularly in summer.

Gallic acid induces necroptosis via TNF-α signaling pathway in activated hepatic stellate cells.

Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), a natural phenolic acid widely found in gallnuts, tea leaves and various fruits, possesses several bioactivities against inflammation, oxidation, and carcinogenicity. The beneficial effect of GA on the reduction of animal hepatofibrosis has been indicated due to its antioxidative property. However, the cytotoxicity of GA autoxidation causing cell death has also been reported. Herein, we postulated that GA might target activated hepatic stellate cells (aHSCs), the cell type responsible for hepatofibrosis, to mitigate the process of fibrosis. The molecular cytotoxic mechanisms that GA exerted on aHSCs were then analyzed. The results indicated that GA elicited aHSC programmed cell death through TNF-α-mediated necroptosis. GA induced significant oxidative stress through the suppression of catalase activity and the depletion of glutathione (GSH). Elevated oxidative stress triggered the production of TNF-α facilitating the undergoing of necroptosis through the up-regulation of key necroptotic regulatory proteins TRADD and receptor-interacting protein 3 (RIP3), and the inactivation of caspase-8. Calmodulin and calpain-1 activation were engaged, which promoted subsequent lysosomal membrane permeabilization (LMP). The TNF-α antagonist (SPD-304) and the RIP1 inhibitor (necrostatin-1, Nec-1) confirmed GA-induced TNFR1-mediated necroptosis. The inhibition of RIP1 by Nec-1 diverted the cell death from necroptosis to apoptosis, as the activation of caspase 3 and the increase of cytochrome c. Collectively, this is the first report indicating that GA induces TNF signaling-triggered necroptosis in aHSCs, which may offer an alternative strategy for the amelioration of liver fibrosis.

New 6-hydroxyeunicellins from a soft coral Cladiella sp.

Two new 6-hydroxyeunicellin diterpenoids, cladieunicellin G (1) and 6-epi-cladieunicellin F (2), were isolated from an Indonesian octocoral Cladiella sp. The structures of eunicellins 1 and 2 were established by spectroscopic methods and 2 was found to be an epimer of the known eunicellin cladieunicellin F (3). Eunicellin 2 displayed inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.

Display of Fibrobacter succinogenes ß-glucanase on the cell surface of Lactobacillus reuteri.

The aim of this study was to display a rumen bacterial ß-glucanase on the cell surface of a probiotic Lactobacillus reuteri strain. The ß-glucan degrading ability and the adhesion capability of the genetically modified strain were evaluated. The ß-glucanase (Glu) from Fibrobacter succinogenes was fused to the C-terminus of collagen-binding protein (Cnb) from L. reuteri and then expressed by L. reuteri Pg4 as a recombinant Cnb-Glu-His(6) fusion protein. Confocal immunofluorescence microscopy and flow cytometric analysis of the transformed strain L. reuteri pNZ-cnb/glu demonstrated that Cnb-Glu-His(6) fusion protein was displayed on its cell surface. In addition, L. reuteri pNZ-cnb/glu acquired the capacity to break down barley ß-glucan and showed higher adhesion capability, in comparison with the parental strain L. reuteri Pg4. To the best of the authors' knowledge, this is the first report of successful display of fibrolytic enzymes on the cell surface of intestinal lactobacilli.

Ocular biocompatibility of carbodiimide cross-linked hyaluronic acid hydrogels for cell sheet delivery carriers.

Due to its innocuous nature, hyaluronic acid (HA) is one of the most commonly used biopolymers for ophthalmic applications. We recently developed a cell sheet delivery system using carbodiimide cross-linked HA carriers. Chemical cross-linking provides an improvement in stability of polymer gels, but probably causes toxic side-effects. The aim of this study was to investigate the ocular biocompatibility of HA hydrogels cross-linked by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC). HA discs without cross-linking and glutaraldehyde (GTA) cross-linked HA samples were used for comparison. The disc implants were inserted in the anterior chamber of rabbit eyes for 24 weeks and characterized by slit-lamp biomicroscopy, histology and scanning electron microscopy. The ophthalmic parameters obtained from biomicroscopic examinations were also scored to provide a quantitative grading system. Results of this study showed that the HA discs cross-linked with EDC had better ocular biocompatibility than those with GTA. The continued residence of GTA cross-linked HA implants in the intraocular cavity elicited severe tissue responses and significant foreign body reactions, whereas no adverse inflammatory reaction was observed after contact with non-cross-linked HA or EDC cross-linked HA samples. It is concluded that the cross-linking agent type gives influence on ocular biocompatibility of cell carriers and the EDC-HA hydrogel is an ideal candidate for use as an implantable material in cell sheet delivery applications.

Low Bloom strength gelatin as a carrier for potential use in retinal sheet encapsulation and transplantation.

Retinal transplantation aims to restore vision for patients suffering from retinitis pigmentosa and age-related macular degeneration. Because the retinal sheets are fragile in nature, it is difficult to maintain graft integrity during surgical manipulation and after transplantation. In the present work, we report the feasibility of applying sandwich-like gelatin membranes as encapsulating carriers for retinal sheet transplantation applications. The relationship between the Bloom index of gelatin and the functionality of carrier membranes was studied by determinations of mechanical property, dissolution degree, melting point, cytocompatibility, biocompatibility, and transplant transfer and encapsulation efficiency. Irrespective of their Bloom strength, the gelatin membranes had a thickness sufficient to provide mechanical support for retinal sheets and would be beneficial to overcome the fragility of transplants during intraocular delivery. It was found that the lower the Bloom value of gelatin, the lower melting point of membranes. This allowed for easy fabrication of a stable sandwich-like encapsulating structure at 37 degrees C. The gelatins with lower Bloom strengths could possibly be dissolved to an extent required for the establishment of close contact between the retinal grafts and defective tissues. In addition, the carrier membranes made from the gelatins with low Bloom values showed a relatively higher cytocompatibility and biocompatibility as well as a higher transfer and encapsulation efficiency as compared to those with high Bloom values. It is concluded that the effect of Bloom index of gelatin plays a significant role in the membrane functionality and the gelatins with low Bloom values have substantial potential to be further developed as effective encapsulating carriers for the intraocular delivery of retinal sheets.

Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators.

Spilanthes acmella (Paracress), a common spice, has been administered as a traditional folk medicine for years to cure toothaches, stammering, and stomatitis. Previous studies have demonstrated its diuretic, antibacterial, and anti-inflammatory activities. However, the active compounds contributing to the anti-inflammatory effect have seldom been addressed. This study isolates the active compound, spilanthol, by a bioactivity-guided approach and indicates significant anti-inflammatory activity on lipopolysaccharide-activated murine macrophage model, RAW 264.7. The anti-inflammatory mechanism of paracress is also investigated. Extracts of S. acmella are obtained by extraction with 85% ethanol, followed by liquid partition against hexane, chloroform, ethyl acetate, and butanol. The ethyl acetate extract exhibits a stronger free radical scavenging capacity than other fractions do, as determined by DPPH and ABTS radical scavenging assays. The chloroform extract significantly inhibits nitric oxide production ( p < 0.01) and is selected for further fractionation to yield the active compound, spilanthol. The diminished levels of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) mRNA and protein expression support the postulation that spilanthol inhibits proinflammatory mediator production at the transcriptional and translational levels. Additionally, the LPS-stimulated IL-1beta, IL-6, and TNF-alpha productions are dose-dependently reduced by spilanthol. The LPS-induced phosphorylation of cytoplasmic inhibitor-kappaB and the nuclear NF-kappaB DNA binding activity are both restrained by spilanthol. Results of this study suggest that spilanthol, isolated from S. acmella, attenuates the LPS-induced inflammatory responses in murine RAW 264.7 macrophages partly due to the inactivation of NF-kappaB, which negatively regulates the production of proinflammatory mediators.