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1.
Trends Genet ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906738

ABSTRACT

Cell-cell interactions orchestrate complex functions in multicellular organisms, forming a regulatory network for diverse biological processes. Their disruption leads to disease states. Recent advancements - including single-cell sequencing and spatial transcriptomics, coupled with powerful bioengineering and molecular tools - have revolutionized our understanding of how cells respond to each other. Notably, spatial transcriptomics allows us to analyze gene expression changes based on cell proximity, offering a unique window into the impact of cell-cell contact. Additionally, computational approaches are being developed to decipher how cell contact governs the symphony of cellular responses. This review explores these cutting-edge approaches, providing valuable insights into deciphering the intricate cellular changes influenced by cell-cell communication.

2.
Toxics ; 12(3)2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38535908

ABSTRACT

Investigating the impact of urinary mercury and cadmium on anthropometric parameters in Korean children is crucial amid growing concerns about heavy metal exposure and childhood growth. Using data from the Korean National Environmental Health Survey (2015-2017), we assessed age- and sex-specific associations of urinary mercury and cadmium with height and body mass index (BMI) z-scores in 1458 children aged 3-5 (n = 571) and 6-11 years (n = 887). Overall, 5.0% had stunted height (3-5 years: 6.9%, 6-11 years: 3.8%), whereas older children exhibited higher overweight/obesity prevalence (29.2%) than younger ones did (22.2%). In 3-5-year-old boys, urinary mercury correlated negatively with height z-scores (p < 0.001), whereas in girls, urinary cadmium correlated positively (p = 0.015). Boys aged 6-11 years showed positive associations between mercury/cadmium levels and BMI z-scores (p = 0.012). Logistic regression indicated associations between urinary mercury and stunted height likelihood (p = 0.001) and between urinary cadmium and reduced overweight likelihood (p = 0.039) in 3-5-year-old boys. In boys aged 6-11 years, urinary cadmium levels were positively associated with overweight likelihood (p = 0.003). This study underscores the link between elevated urinary mercury, cadmium levels, and growth disruptions in Korean children, emphasizing the need for public health strategies for reducing childhood heavy metal exposure.

3.
Small ; 20(4): e2304051, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37612793

ABSTRACT

Quantum-dot light-emitting diodes (QD-LEDs) have gained attention as potential display technologies. However, the solvents used to dissolve a polymeric hole transport layer (HTL) are hazardous to both humans and the environment. Additionally, intermixing the HTL and QD layers presents a significant challenge when fabricating inverted QD-LEDs. Here, a green solvent selection procedure to achieve good device performance and environmental safety in QD-LEDs is established. This procedure utilizes Hansen solubility parameters and surface roughness to identify a set of solvents that do not lower the device performance by avoiding interlayer mixing or a rough interface. The CHEM21 solvent selection guide is used to screen for environmentally hazardous solvents. Finally, cyclopentanone (CPO) is selected as the optimal HTL solvent from among 16 candidates. Using CPO improves the maximum luminescence by ≈1.6 times and the maximum current efficiency by ≈12.6 times, compared to that of conventional devices using hazardous chlorobenzene. Solvent selection is critical for the fabrication of green and high-performance inverted QD-LEDs, particularly for large display panels that require n-type oxide thin-film transistors.

4.
Allergol Int ; 73(1): 3-12, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37752021

ABSTRACT

The ongoing COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study is a prospective birth cohort investigating the origin and natural courses of childhood allergic diseases, including atopic dermatitis, food allergy, allergic rhinitis and asthma, with long-term prognosis. Initiated under the premise that allergic diseases result from a complex interplay of immune development alterations, environmental exposures, and host susceptibility, the COCOA study explores these dynamic interactions during prenatal and postnatal periods, framed within the hygiene and microbial hypotheses alongside the developmental origins of health and disease (DOHaD) hypothesis. The scope of the COCOA study extends to genetic predispositions, indoor and outdoor environmental variables affecting mothers and their offsprings such as outdoor and indoor air pollution, psychological factors, diets, and the microbiomes of skin, gut, and airway. We have embarked on in-depth investigations of diverse risk factors and the pathophysiological underpinnings of allergic diseases. By employing multi-omics approaches-proteomics, transcriptomics, and metabolomics-we gain deeper insights into the distinct pathophysiological processes across various endotypes of childhood allergic diseases, incorporating the exposome using extensive resources within the COCOA study. Integration with large-scale datasets, such as national health insurance records, enhances robustness and mitigates potential limitations inherent to birth cohort studies. As part of global networks focused on childhood allergic diseases, the COCOA study fosters collaborative research across multiple cohorts. The findings from the COCOA study are instrumental in informing precision medicine strategies for childhood allergic diseases, underpinning the establishment of disease trajectories.


Subject(s)
Asthma , Dermatitis, Atopic , Food Hypersensitivity , Rhinitis, Allergic , Pregnancy , Female , Humans , Prospective Studies , Food Hypersensitivity/complications
5.
Mol Syst Biol ; 19(11): e11670, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37815040

ABSTRACT

Cells have evolved their communication methods to sense their microenvironments and send biological signals. In addition to communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach to investigate cell neighbor-dependent gene expression (CellNeighborEX) in spatial transcriptomics (ST) data. To categorize cells based on their microenvironment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on ST technologies. For each cell type, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. We found that cells express different genes depending on their neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. Those genes are associated with critical biological processes such as development or metastases. We further validated that gene expression is induced by neighboring partners via spatial visualization. The neighbor-dependent gene expression suggests new potential genes involved in cell-cell interactions beyond what ligand-receptor co-expression can discover.


Subject(s)
Liver Neoplasms , Transcriptome , Animals , Mice , Transcriptome/genetics , Gene Expression Profiling , Brain , Cell Communication , Tumor Microenvironment
6.
J Colloid Interface Sci ; 649: 132-139, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37348332

ABSTRACT

Quantum-dot (QDs) polymer composite films, which are key components in recent display applications, require improved photoluminescence (PL) intensity and color conversion efficiency for better display quality and low power consumption. In this study, we developed a novel approach to improve the photoluminescence (PL) of quantum dot (QDs)-polymer nanocomposite films. This was achieved by incorporating CO2 micropores and scattering particles into QD-embedded photopolymerizable polymer films. CO2 micropores were generated by the decomposition of KHCO3 in the film. The CO2 micropores, along with the partially decomposed KHCO3 microparticles, act as a scattering medium that increases the photon absorbance and improves the PL intensity. The effect of KHCO3 annealing temperature on various optical properties is investigated, and it is found that a large number of uniform micropores are created in the film at an optimal temperature, 110 ℃. Compared to an ordinary QD-polymer film, the PL of the QD-hybrid-foamed polymer film increases by 4.2 times. This method is fast and economically efficient, and provides insights into the design of high-performance optoelectronic devices.

7.
Allergy Asthma Immunol Res ; 15(2): 145-159, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37021502

ABSTRACT

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

8.
Allergy Asthma Immunol Res ; 15(1): 19-31, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36693355

ABSTRACT

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life (QOL) of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence while considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines of AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine (INAH) combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

9.
Asian Pac J Allergy Immunol ; 41(1): 60-66, 2023 Mar.
Article in English | MEDLINE | ID: mdl-32416664

ABSTRACT

BACKGROUND: Maternal anxiety during pregnancy has been previously reported to be associated with atopic dermatitis (AD) in offspring. The potential mechanism is not yet proven but epigenetic change may be suggested. OBJECTIVE: We examined whether maternal anxiety during pregnancy may alter placental DNA methylation, then develop AD in the offspring. METHODS: We evaluated maternal anxiety at 36 weeks of gestation by self-reported questionnaires, the State-Trait Anxiety Inventory-Trait subscale (STAI-T), in the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) study. AD was diagnosed at 6 months of age by pediatric allergists. We stratified the subjects into four groups according to the STAI score of mothers and diagnosis of AD in children. Placental genome-wide methylation microarray was analyzed using Infinium 450K BeadChip and selected genes were validated by pyrosequencing. RESULTS: From microarray, several differential methylation sites were identified in AD and healthy subjects and in total subjects, regarding to the STAI scores. Among differential methylation sites in microarray, six sites were selected for pyrosequencing. And site of matrix metalloproteinases 27 (MMP27) among 6 sites showed decreased methylation in AD infants with high STAI mothers compared to healthy infants with low STAI mothers. CONCLUSIONS: Epigenetic change in placenta can be a suggesting mechanism for the development of AD in offspring at 6 months of age associated with maternal anxiety during pregnancy and MMP27 may be a candidate gene.


Subject(s)
Asthma , Dermatitis, Atopic , Pregnancy , Infant , Female , Humans , Child , DNA Methylation , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/genetics , Placenta , Anxiety/genetics
10.
Asian Pac J Allergy Immunol ; 41(3): 220-226, 2023 Sep.
Article in English | MEDLINE | ID: mdl-35278062

ABSTRACT

BACKGROUND: Exposure to particulate matter (PM) has been known to develop asthma in children and the oxidative stress-related mechanisms are suggested. For the development of asthma, not only the exposure dose but also the critical window and the risk modifying factors should be evaluated. OBJECTIVE: We investigated whether prenatal exposure to PM10 increases the risk of childhood asthma and evaluated the modifying factors, such as gender and reactive oxidative stress-related gene. METHODS: A general population-based birth cohort, the Panel Study of Korean Children (PSKC), including 1572 mother-baby dyads was analyzed. Children were defined to have asthma at age 7 when a parent reported physician-diagnosed asthma. Exposure to PM10 during pregnancy was estimated by land-use regression models based on national monitoring system. TaqMan method was used for genotyping nuclear factor, erythroid 2-related factor, NRF2 (rs6726395). A logistic Bayesian distributed lag interaction model (BDLIM) was used to evaluate the associations between prenatal PM10 exposure and childhood asthma by gender and NRF2. RESULTS: Exposure to PM10 during pregnancy was associated with the development of asthma (aOR 1.03, 95% CI 1.001.06). Stratifying by gender and NRF2 genotype, exposure to PM10 during 26-28 weeks gestation increased the risk of childhood asthma, especially in boys with NRF2 GG genotype. CONCLUSIONS: A critical window for PM10 exposure on the development of childhood asthma was during 26-28 weeks of gestation, and this was modified by gender and NRF2 genotype.


Subject(s)
Air Pollutants , Air Pollution , Asthma , Prenatal Exposure Delayed Effects , Infant , Child , Male , Female , Pregnancy , Humans , Particulate Matter/adverse effects , Particulate Matter/analysis , NF-E2-Related Factor 2/genetics , Bayes Theorem , Prenatal Exposure Delayed Effects/epidemiology , Asthma/etiology , Asthma/genetics , Genotype , Air Pollutants/adverse effects , Air Pollution/adverse effects
11.
Clin Exp Pediatr ; 66(3): 134-141, 2023 03.
Article in English | MEDLINE | ID: mdl-36550772

ABSTRACT

BACKGROUND: Human coronaviruses (HCoV) cause mild upper respiratory infections; however, in 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, causing an acute respiratory disease pandemic. Coronaviruses exhibit marked epidemiological and clinical differences. PURPOSE: This study compared the clinical, laboratory, and radiographic findings of children infected with SARS-CoV-2 versus HCoV. METHODS: SARS-CoV-2 data were obtained from the Korea Disease Control and Prevention Agency (KDCA) registry and 4 dedicated coronavirus disease 2019 (COVID-19) hospitals. Medical records of children admitted with a single HCoV infection from January 2015 to March 2020 were collected from 10 secondary/tertiary hospitals. Clinical data included age, sex, underlying disease, symptoms, test results, imaging findings, treatment, and length of hospital stay. RESULTS: We compared the clinical characteristics of children infected with HCoV (n=475) to those of children infected with SARS-CoV-2 (272 from KDCA, 218 from COVID-19 hospitals). HCoV patients were younger than KDCA patients (older than 9 years:3.6% vs. 75.7%; P<0.001) and patients at COVID-19 hospitals (2.0±2.9 vs 11.3±5.3; P<0.001). Patients with SARS-CoV-2 infection had a lower rate of fever (26.6% vs. 66.7%; P<0.001) and fewer respiratory symptoms than those with HCoV infection. Clinical severity, as determined by oxygen therapy and medication usage, was worse in children with HCoV infection. Children and adolescents with SARS-CoV-2 had less severe symptoms. CONCLUSION: Children and adolescents with COVID-19 had a milder clinical course and less severe disease than those with HCoV in terms of symptoms at admission, examination findings, and laboratory and radiology results.

12.
Clin Respir J ; 16(11): 756-767, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36205104

ABSTRACT

INTRODUCTION: Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide-sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children. METHODS: A prospective multicenter study was conducted in 1063 children <18 years old in July 2018-June 2020. The 454 had a positive M. pneumoniae polymerase chain reaction assay. RESULTS: Most subjects had MRMP (78.4%), and all mutated strains had the A2063G transition. We defined MRMP* (n = 285) as MRMP pneumonia requiring admission and MSMP* (n = 72) as MSMP pneumonia requiring admission. Patients with MRMP pneumonia were older, more likely to have segmental/lobar pneumonia, and had more febrile days than those with MSMP pneumonia. C-reactive protein (CRP), lactate dehydrogenase (LDH), and percentage neutrophils were more strongly associated with MRMP* than MSMP* groups. Percentage neutrophils, CRP, and alanine aminotransferase significantly changed between admission and follow-up measurements in patients with MRMP* (P < 0.05). The duration of admission positively correlated with the number of febrile days after initiation of antibiotic medication and laboratory variables (white blood cell count, CRP, and aspartate aminotransferase [AST]) (P < 0.05). Random forest analysis indicated that the number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission was over five. CONCLUSIONS: This study indicated that children with M. pneumoniae pneumonia with a higher number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission were more likely to have prolonged admission duration.


Subject(s)
Mycoplasma pneumoniae , Pneumonia, Mycoplasma , Child , Humans , Adolescent , Mycoplasma pneumoniae/genetics , Prospective Studies , Drug Resistance, Bacterial , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/epidemiology , Macrolides/therapeutic use , Macrolides/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , C-Reactive Protein
13.
Mol Syst Biol ; 18(9): e11080, 2022 09.
Article in English | MEDLINE | ID: mdl-36065846

ABSTRACT

Characterization of tissue architecture promises to deliver insights into development, cell communication, and disease. In silico spatial domain retrieval methods have been developed for spatial transcriptomics (ST) data assuming transcriptional similarity of neighboring barcodes. However, domain retrieval approaches with this assumption cannot work in complex tissues composed of multiple cell types. This task becomes especially challenging in cellular resolution ST methods. We developed Vesalius to decipher tissue anatomy from ST data by applying image processing technology. Vesalius uniquely detected territories composed of multiple cell types and successfully recovered tissue structures in high-resolution ST data including in mouse brain, embryo, liver, and colon. Utilizing this tissue architecture, Vesalius identified tissue morphology-specific gene expression and regional specific gene expression changes for astrocytes, interneuron, oligodendrocytes, and entorhinal cells in the mouse brain.


Subject(s)
Transcriptome , Animals , Mice , Transcriptome/genetics
14.
Clin Exp Pediatr ; 65(7): 348-349, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35508310
15.
BMC Infect Dis ; 22(1): 330, 2022 Apr 04.
Article in English | MEDLINE | ID: mdl-35379181

ABSTRACT

BACKGROUND: Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. METHODS: The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. RESULTS: A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. CONCLUSIONS: This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.


Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia, Mycoplasma , Adolescent , Child , Community-Acquired Infections/microbiology , Humans , Multiplex Polymerase Chain Reaction/methods , Staphylococcus aureus
16.
J Clin Med ; 11(2)2022 Jan 08.
Article in English | MEDLINE | ID: mdl-35054002

ABSTRACT

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

17.
Yonsei Med J ; 62(8): 708-716, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34296548

ABSTRACT

PURPOSE: To determine the efficacy of a potassium-competitive acid blocker (P-CAB)-based first-line eradication therapy with bismuth compared with that of proton pump inhibitor-based first-line therapy with bismuth. MATERIALS AND METHODS: Eradication-naive H. pylori-infected patients were consecutively enrolled from January to November 2020. Before approval of the P-CAB-based eradication therapy, twice daily administration of a regimen containing lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and bismuth potassium citrate 300 mg was prescribed for 7 days. After approval, lansoprazole was replaced with tegoprazan (50 mg). Clarithromycin resistance was examined in patients who underwent gastroscopic biopsy at our center. Efficacy was assessed via the 13C-urea breath test. RESULTS: Of the 381 eradication-naive patients, eradication was successful in 88.3% (151/171) treated with tegoprazan and 82.8% (140/169) treated with lansoprazole in per-protocol analysis (p=0.151). In intention-to-treat analysis, eradication rates were 78.8% (152/193) in the tegoprazan and 74.5% (140/188) in the lansoprazole group (p=0.323). Clarithromycin resistance was observed in 30 (20.1%) of the 148 patients (74 from each group), and only four of the 16 clarithromycin-resistant patients in the tegoprazan group achieved successful eradication. Clarithromycin resistance [odds ratio (OR)=42.1, 95% confidence intervals (CIs)=12.6-141.0] and poor patient compliance (OR=17.1, 95% CIs=1.6-189.1) were independent risk factors for eradication failure. CONCLUSION: In eradication-naive patients, eradication success rates for 7-day first-line triple therapy regimen exceeded 82% with bismuth administration. In clarithromycin-resistant patients, neither tegoprazan 50 mg nor lansoprazole 30 mg achieved acceptable eradication rates when administered twice daily for 7 days.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Anti-Bacterial Agents/therapeutic use , Bismuth/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/drug therapy , Humans , Potassium , Treatment Outcome
18.
Environ Res ; 200: 111640, 2021 09.
Article in English | MEDLINE | ID: mdl-34302828

ABSTRACT

Prenatal particulate matter <2.5 µm (PM2.5) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM2.5 levels and birth weight (BW). PM2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism.


Subject(s)
Air Pollutants , Air Pollution , Prenatal Exposure Delayed Effects , Air Pollutants/analysis , Air Pollutants/toxicity , Arrestins , Bayes Theorem , Child , DNA Methylation , Female , Humans , Infant, Newborn , Male , Maternal Exposure/adverse effects , Particulate Matter/analysis , Particulate Matter/toxicity , Pregnancy
19.
Nat Mater ; 20(6): 892-903, 2021 06.
Article in English | MEDLINE | ID: mdl-33495631

ABSTRACT

The basement membrane (BM) is a special type of extracellular matrix and presents the major barrier cancer cells have to overcome multiple times to form metastases. Here we show that BM stiffness is a major determinant of metastases formation in several tissues and identify netrin-4 (Net4) as a key regulator of BM stiffness. Mechanistically, our biophysical and functional analyses in combination with mathematical simulations show that Net4 softens the mechanical properties of native BMs by opening laminin node complexes, decreasing cancer cell potential to transmigrate this barrier despite creating bigger pores. Our results therefore reveal that BM stiffness is dominant over pore size, and that the mechanical properties of 'normal' BMs determine metastases formation and patient survival independent of cancer-mediated alterations. Thus, identifying individual Net4 protein levels within native BMs in major metastatic organs may have the potential to define patient survival even before tumour formation. The ratio of Net4 to laminin molecules determines BM stiffness, such that the more Net4, the softer the BM, thereby decreasing cancer cell invasion activity.


Subject(s)
Basement Membrane/metabolism , Mechanical Phenomena , Neoplasm Metastasis , Biomechanical Phenomena , Cell Line, Tumor , Humans , Netrins/metabolism
20.
Entropy (Basel) ; 22(9)2020 Sep 04.
Article in English | MEDLINE | ID: mdl-33286756

ABSTRACT

Robustness and evolvability are essential properties to the evolution of biological networks. To determine if a biological network is robust and/or evolvable, it is required to compare its functions before and after mutations. However, this sometimes takes a high computational cost as the network size grows. Here, we develop a predictive method to estimate the robustness and evolvability of biological networks without an explicit comparison of functions. We measure antifragility in Boolean network models of biological systems and use this as the predictor. Antifragility occurs when a system benefits from external perturbations. By means of the differences of antifragility between the original and mutated biological networks, we train a convolutional neural network (CNN) and test it to classify the properties of robustness and evolvability. We found that our CNN model successfully classified the properties. Thus, we conclude that our antifragility measure can be used as a predictor of the robustness and evolvability of biological networks.

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