Publications by authors named "Jiu-Yao Wang"

100 Publications

Effect of a Probiotic Combination in an Experimental Mouse Model and Clinical Patients With Chronic Kidney Disease: A Pilot Study.

Front Nutr 2021 31;8:661794. Epub 2021 May 31.

Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.

The aim of the present study was to evaluate whether probiotic administration could slow declining renal function. C57BL/6 mice (6-8 weeks of age, male) were fed a diet supplemented with adenine to induce chronic kidney disease (CKD). The experimental groups were additionally supplemented with 10 colony-forming units (CFU)/day (high-dose) and 10 CFU/day (low-dose) probiotics containing (TYCA06), subspecies (BLI-02), and (VDD088). Renal function and histology were examined. Patients with stage 3-5 CKD and not on dialysis were recruited from July 2017 to January 2019. Two capsules of probiotics containing 2.5 × 10 CFU with the same composition were administered twice daily for 6 months. The decline in the estimated glomerular filtration rate (eGFR) was measured before and after the intervention. In addition, changes in the serum endotoxin and cytokine levels, gastrointestinal symptom scores, and the stool microbiota were measured. Probiotics could attenuate renal fibrosis and improve renal function in CKD mice. Thirty-eight patients completed the 6-month study. The mean baseline eGFR was 30.16 ± 16.52 ml/min/1.73 m. The rate of decline in the eGFR was significantly slower, from -0.54 (-0.18, -0.91) to 0.00 (0.48, -0.36) ml/min/1.73 m/month ( = 0.001) after 6 months of treatment. The serum levels of TNF-α, IL-6, IL-18, and endotoxin were significantly decreased after probiotic administration. Borborygmus and flatulence scores, as well as stool formation improved significantly. The abundance of and in the stool microbiota increased significantly. In conclusion, a combination of probiotics might attenuate renal function deterioration in CKD mice and human patients.
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http://dx.doi.org/10.3389/fnut.2021.661794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200566PMC
May 2021

Human Surfactant Protein D Binds Spike Protein and Acts as an Entry Inhibitor of SARS-CoV-2 Pseudotyped Viral Particles.

Front Immunol 2021 14;12:641360. Epub 2021 May 14.

Center for Allergy & Clinical Immunology Research (ACIR), National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Human SP-D is a potent innate immune molecule whose presence at pulmonary mucosal surfaces allows its role in immune surveillance against pathogens. Higher levels of serum SP-D have been reported in the patients with severe acute respiratory syndrome coronavirus (SARS-CoV). Studies have suggested the ability of human SP-D to recognise spike glycoprotein of SARS-CoV; its interaction with HCoV-229E strain leads to viral inhibition in human bronchial epithelial (16HBE) cells. Previous studies have reported that a recombinant fragment of human SP-D (rfhSP-D) composed of 8 Gly-X-Y repeats, neck and CRD region, can act against a range of viral pathogens including influenza A Virus and Respiratory Syncytial Virus , and . In this context, this study was aimed at examining the likely protective role of rfhSP-D against SARS-CoV-2 infection. rfhSP-D showed a dose-responsive binding to S1 spike protein of SARS-CoV-2 and its receptor binding domain. Importantly, rfhSP-D inhibited interaction of S1 protein with the HEK293T cells overexpressing human angiotensin converting enzyme 2 (hACE2). The protective role of rfhSP-D against SARS-CoV-2 infection as an entry inhibitor was further validated by the use of pseudotyped lentiviral particles expressing SARS-CoV-2 S1 protein; ~0.5 RLU fold reduction in viral entry was seen following treatment with rfhSP-D (10 µg/ml). These results highlight the therapeutic potential of rfhSP-D in SARS-CoV-2 infection and merit pre-clinical studies in animal models.
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http://dx.doi.org/10.3389/fimmu.2021.641360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161545PMC
June 2021

Decreasing ten-year (2008-2018) trends of the prevalence of childhood asthma and air pollution in Southern Taiwan.

World Allergy Organ J 2021 May 29;14(5):100538. Epub 2021 Apr 29.

Division of Allergy and Clinical Immunology, Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.

Background: Asthma is a common pediatric chronic respiratory disease worldwide. Previous studies showed the prevalence of childhood asthma increased in developed countries as well as in Taiwan in the late 20th century. Recently, several reports from different parts of the world showed a reversed trend in this epidemic of childhood asthma prevalence. This study investigated the trend of childhood asthma through serial cross-section questionnaire surveys in the southern part of Taiwan, and identified associated factors related to this trend in elementary school children.

Methods: We used the Chinese version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to assess the asthma status of elementary school students aged 6-12 years in Tainan city in 3 independent study periods, namely, 2008-2009, 2010-2012, and 2017-2018. We assessed the trend of "asthma" and "related respiratory symptoms" across 3 study periods.

Results: Of the 19,633 respondents, 17,545 (89.4%) completed the questionnaires. After adjustment for covariates, the prevalence of asthma and related respiratory symptoms was significantly lower in 2017-2018 than in the 2 earlier periods. Among the protective factors, the increasing rate of breastfeeding might be partly responsible for the observed reduced prevalence of current asthma and exercise-induced wheeze, but not physician-diagnosed asthma. The presence of pets in the house was the risk factor that correlated with the prevalence of nocturnal cough. Pearson correlation analysis showed a significant correlation of the prevalence of physician-diagnosed asthma, current asthma, and exercise-induced wheezing with the concentrations of air pollutant particles with aerodynamic diameter ≤10 μM (PM) (r = 0.84, 0.77 and 0.81, respectively).

Conclusion: The prevalence of asthma and related respiratory symptoms has declined in elementary school-age children in southern Taiwan. The increased prevalence of breastfeeding, decreased rate of the presence of pets in the house, and improvement in outdoor air pollution seem to be related to this decreasing trend of asthma in school children. Our findings will provide the scientific base to empower prevention policy to reverse the trend of childhood asthma prevalence.

Trial Registration: N/A.
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http://dx.doi.org/10.1016/j.waojou.2021.100538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102795PMC
May 2021

Development and Application of Human Coronavirus Protein Microarray for Specificity Analysis.

Anal Chem 2021 06 19;93(21):7690-7698. Epub 2021 May 19.

Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan 701, Taiwan, ROC.

Coronavirus is an enveloped RNA virus that causes mild to severe respiratory diseases in humans, including HKU1-CoV, 229E-CoV, NL63-CoV, OC43-CoV, SARS-CoV, MERS-CoV, and SARS-CoV-2. Due to the outbreak of SARS-CoV-2, it is important to identify the patients and investigate their immune responses. Protein microarray is one of the best platforms to profile the antibodies in the blood because of its fast, multiplexed, and sensitive nature. To fully understand the immune responses and biological specificities, this study developed a human coronavirus (HCoV) protein microarray and included all seven human coronaviruses and three influenza viruses. Each protein was printed in triplicate and formed 14 identical blocks per array. The HCoV protein microarray showed high reproducibility and sensitivity to the monoclonal antibodies against spike and nucleocapsid protein with detection limits of 10-200 pg. The HCoV proteins that were immobilized on the array were properly folded and functional by showing interactions with a known human receptor, e.g., ACE2. By profiling the serum IgG and IgA from 32 COVID-19 patients and 36 healthy patients, the HCoV protein microarray demonstrated 97% sensitivity and 97% specificity with two biomarkers. The results also showed the cross-reactivity of IgG and IgA in COVID-19 patients to spike proteins from various coronaviruses, including that from SARS-CoV, HKU1-CoV, and OC43-CoV. Finally, an innate immune protein named surfactant protein D showed broad affinities to spike proteins in all human coronaviruses. Overall, the HCoV protein microarray is multiplexed, sensitive, and specific, which is useful in diagnosis, immune assessment, biological development, and drug screening.
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http://dx.doi.org/10.1021/acs.analchem.1c00614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146142PMC
June 2021

Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children.

JAMA Pediatr 2021 Apr 19. Epub 2021 Apr 19.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Importance: The adverse effects from the long-term use of oral corticosteroids are known, but, to our knowledge, few studies have reported the risk of corticosteroid bursts, particularly among children.

Objective: To quantify the associations of corticosteroid bursts with severe adverse events, including gastrointestinal (GI) bleeding, sepsis, pneumonia, and glaucoma, in children.

Design, Setting, And Participants: This cohort study used data derived from the National Health Insurance Research Database in Taiwan from January 1, 2013, to December 31, 2017, on children younger than 18 years of age and used a self-controlled case series design. Data were analyzed from January 1 to July 30, 2020.

Exposure: Oral corticosteroid bursts (defined as oral corticosteroid use for ≤14 days).

Main Outcomes And Measures: Incidence rates were calculated of 4 severe adverse events (GI bleeding, sepsis, pneumonia, and glaucoma) in children who did or did not receive corticosteroid bursts. Conditional fixed-effect Poisson regression was used to estimate incidence rate ratios (IRRs) of severe adverse events within 5 to 30 days and 31 to 90 days after initiation of corticosteroid bursts.

Results: Among 4 542 623 children, 23% (1 064 587; 544 268 boys [51.1%]; mean [SD] age, 9.7 [5.8] years) were prescribed a single corticosteroid burst. The most common indications were acute respiratory tract infections and allergic diseases. The incidence rate differences per 1000 person-years between children administered a single corticosteroid burst and those not prescribed corticosteroids were 0.60 (95% CI, 0.55-0.64) for GI bleeding, 0.03 (95% CI, 0.02-0.05) for sepsis, 9.35 (95% CI, 9.19-9.51) for pneumonia, and 0.01 (95% CI, 0.01-0.03) for glaucoma. The IRRs within 5 to 30 days after initiating corticosteroid bursts were 1.41 (95% CI, 1.27-1.57) for GI bleeding, 2.02 (95% CI, 1.55-2.64) for sepsis, 2.19 (95% CI, 2.13-2.25) for pneumonia, and 0.98 (95% CI, 0.85-1.13) for glaucoma; the IRRs within the subsequent 31 to 90 days were 1.10 (95% CI, 1.02-1.19) for GI bleeding, 1.08 (95% CI, 0.88-1.32) for sepsis, 1.09 (95% CI, 1.07-1.11) for pneumonia, and 0.95 (95% CI, 0.85-1.06) for glaucoma.

Conclusions And Relevance: This study suggests that corticosteroid bursts, which are commonly prescribed for children with respiratory and allergic conditions, are associated with a 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days.
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http://dx.doi.org/10.1001/jamapediatrics.2021.0433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056312PMC
April 2021

Adjunct therapy with probiotics for chronic urticaria in children: randomised placebo-controlled trial.

Allergy Asthma Clin Immunol 2021 Apr 17;17(1):39. Epub 2021 Apr 17.

Centre for Allergy and Clinical Immunology Research (ACIR), College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Backgrounds: Chronic urticaria is a common disorder of the skin, characterised by recurrent skin wheals and angioedema. Recent reports have shown that altered diversity and composition of the gut microbiota may lead to imbalances in immune regulation, a causal factor in the occurrence of chronic urticaria.

Objective: This study aimed to evaluate the efficacy of the Yimingjia probiotic formula in the adjuvant treatment of chronic urticaria in children.

Methods: We enrolled 206 children with confirmed diagnoses of chronic urticaria and randomly assigned them to the treatment (n = 104) or placebo group (n = 102). The children in each group were treated with desloratadine dry suspension, and those in the treatment group also received Yimingjia. Clinical efficacy was evaluated at 1, 2 and 4 weeks.

Results: Clinical symptom scores did not differ significantly at weeks 1 and 2 (p > 0.05), but at 4 weeks, wheal size and attack frequency were significantly reduced in the treatment group (p = 0.049 and 0.03, respectively). The overall response rate (significant improvement + complete response) significantly differed between the treatment (80.8%) and placebo groups (62.5%) (χ = 4.20, p = 0.04).

Conclusion: Adjunct therapy with Yimingjia was safe and effective at 4 weeks in the treatment of chronic urticaria in children. The study was registered under trial number NCT03328897.
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http://dx.doi.org/10.1186/s13223-021-00544-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052813PMC
April 2021

Disease tolerance to infection: the immune defense strategy of mitoribosome targeting.

Cell Mol Immunol 2021 Apr 16. Epub 2021 Apr 16.

Center for Allergy and Clinical Immunology Research (ACIR), College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, China.

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http://dx.doi.org/10.1038/s41423-021-00677-wDOI Listing
April 2021

Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy.

Clin Epigenetics 2021 Apr 9;13(1):76. Epub 2021 Apr 9.

Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Cheng-Hsing Campus, No. 1, University Road, Tainan City, Taiwan.

Background: Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases.

Results: Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children's respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (β =  - 1.75, p = 0.015) after adjustment for child's sex, age, BMI, parents' smoking status, allergic history, and education levels, PM, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65-0.99).

Conclusions: Exposure to BBzP in settled dust might increase children's respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.
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http://dx.doi.org/10.1186/s13148-021-01061-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035749PMC
April 2021

Early-life EV-A71 infection augments allergen-induced airway inflammation in asthma through trained macrophage immunity.

Cell Mol Immunol 2021 Feb 13;18(2):472-483. Epub 2021 Jan 13.

Center for Allergy and Clinical Immunology Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China.

Virus-induced asthma is prevalent among children, but its underlying mechanisms are unclear. Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma. Nonetheless, the relationship between systemic virus infections, such as enterovirus infection, and the ensuing effects on allergic asthma development is unknown. Early-life enterovirus infection was correlated with higher risks of allergic diseases in children. Adult mice exhibited exacerbated mite allergen-induced airway inflammation following recovery from EV-A71 infection in the neonatal period. Bone marrow-derived macrophages (BMDMs) from recovered EV-A71-infected mice showed sustained innate immune memory (trained immunity) that could drive naïve T helper cells toward Th2 and Th17 cell differentiation when in contact with mites. Adoptive transfer of EV-A71-trained BMDMs induced augmented allergic inflammation in naïve recipient mice, which was inhibited by 2-deoxy-D-glucose (2-DG) pretreatment, suggesting that trained macrophages following enterovirus infection are crucial in the progression of allergic asthma later in life.
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http://dx.doi.org/10.1038/s41423-020-00621-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027667PMC
February 2021

Climate Change, Air Pollution, and Biodiversity in Asia Pacific and Impact on Respiratory Allergies.

Immunol Allergy Clin North Am 2021 Feb;41(1):63-71

Department of Pediatrics, Center for Allergy and Clinical Immunology Research (ACIR), College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.

Allergic diseases are increasing globally. Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on chronic noncommunicable diseases. Outdoor and indoor air pollution and climate change are increasing. Asia has experienced rapid economic growth, a deteriorating environment, and an increase in allergic diseases to epidemic proportions. Air pollutant levels in Asian countries are substantially higher than in developed countries. Moreover, industrial, traffic-related, and household biomass combustion and indoor pollutants from chemicals and tobacco are major sources of air pollutants. We highlight the major components of pollutants and their impacts on respiratory allergies.
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http://dx.doi.org/10.1016/j.iac.2020.09.008DOI Listing
February 2021

Diagnostic procedures & practices in drug allergy/hypersensitivity: a survey of 13 Asian countries.

Asia Pac Allergy 2020 Oct 15;10(4):e36. Epub 2020 Oct 15.

Department of Pediatrics, Nippon Medical School, Tokyo, Japan.

Background: The issues and challenges in the diagnosis of drug allergy/hypersensitivity among children and adults in Asia are likely to be different from non-Asian countries.

Objective: To study the diagnostic modalities used in the evaluation and management of drug allergy/drug hypersensitivity reactions (DHRs) among member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI).

Methods: A questionnaire comprising 41 questions was circulated electronically to member societies and individual members of APAAACI between January 23, 2020 and March 6, 2020.

Results: Twenty-six respondents from 15 member societies and 1 individual member responded. European DHR guidelines were most commonly used. Skin prick and intradermal testing was used by 100%, with only 60% having access to commercial penicillin skin test reagents. -specific IgE tests were used by 75%, and basophil activation test by 56.3% for immediate DHR. Patch tests were used by 75% in contrast to lymphocyte transformation tests by 25% for nonimmediate DHR. Drug provocation tests were used by 68.8%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (93.3%). Human leukocyte antigen (HLA) genotype testing was mandatory among 25% respondents before new carbamazepine prescriptions, and 8.3% for allopurinol prescriptions.

Conclusions: There was increased use of skin testing for iodinated contrast media hypersensitivity and patch testing for nonimmediate DHR. HLA genotype testing prior to new carbamazepine, allopurinol and abacavir prescriptions remain variable despite strong associations for severe cutaneous adverse reactions with Asian ethnicity. Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across APAAACI member societies.
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http://dx.doi.org/10.5415/apallergy.2020.10.e36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610088PMC
October 2020

Multiplexed Graphene Quantum Dots with Excitation-Wavelength-Independent Photoluminescence, as Two-Photon Probes, and in Ultraviolet-Near Infrared Bioimaging.

ACS Nano 2020 09 24;14(9):11502-11509. Epub 2020 Aug 24.

Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.

In this study, sorted nitrogen-doped graphene quantum dots were prepared and subsequently conjugated with polymers. The synthesized materials exhibited excitation-wavelength-independent photoluminescence emissions ranging from ultraviolet to near-infrared and were 0.9-8.4 nm in size. The materials also exhibited high-photoluminescence quantum yields and excellent two-photon properties. Therefore, in two-photon bioimaging the materials with different emission spectra can be effective two-photon contrast agents. Specific antibodies were used to label organelles in cancer cells and identify nuclear antigens, thereby enabling the simultaneous detection of four targets in cells at a single two-photon excitation wavelength. The sorted nitrogen-doped graphene quantum dot materials were determined to be considerably more advantageous than organic dyes in identifying multiplexed targets, and they can be effective probes in cellular imaging.
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http://dx.doi.org/10.1021/acsnano.0c03915DOI Listing
September 2020

COVID-19 and asthma, the good or the bad?

Allergy 2021 02 20;76(2):565-567. Epub 2020 Jul 20.

School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing, China.

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http://dx.doi.org/10.1111/all.14480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362161PMC
February 2021

Water-Soluble Fullerenol with Hydroxyl Group Dependence for Efficient Two-Photon Excited Photodynamic Inactivation of Infectious Microbes.

Nanoscale Res Lett 2020 May 6;15(1):99. Epub 2020 May 6.

Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan, Republic of China.

We successfully prepared water-soluble fullerenol [C(OH)] that exhibited a high singlet oxygen quantum yield and efficiently generated reactive oxygen species. Additionally, the water-soluble C(OH) with a higher composition of exposed hydroxyl groups had superior two-photon stability and characteristics compared with that with a lower composition of such groups. Therefore, the prepared fullerenol can be an effective two-photon photosensitizer. The water-soluble C(OH) had favorable two-photon properties. During two-photon photodynamic therapy, the water-soluble C(OH) had substantial antimicrobial activity against Escherichia coli at an ultralow-energy level of 211.2 nJ pixel with 800 scans and a photoexcited wavelength of 760 nm.
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http://dx.doi.org/10.1186/s11671-020-03329-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203358PMC
May 2020

AP-32 and GL-104 decrease glycemic levels and attenuate diabetes-mediated liver and kidney injury in db/db mice.

BMJ Open Diabetes Res Care 2020 04;8(1)

Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan

Objectives: Patients with type 2 diabetes mellitus (T2DM) exhibit strong insulin resistance or abnormal insulin production. Probiotics, which are beneficial live micro-organisms residing naturally in the intestinal tract, play indispensable roles in the regulation of host metabolism. However, the detailed mechanisms remain unclear. Here, we evaluate the mechanisms by which probiotic strains mediate glycemic regulation in the host. The findings should enable the development of a safe and natural treatment for patients with T2DM.

Research Designs And Methods: Sugar consumption by more than 20 strains of species was first evaluated. The probiotic strains that exhibited high efficiency of sugar consumption were further coincubated with Caco-2 cells to evaluate the regulation of sugar absorption in gut epithelial cells. Finally, potential probiotic strains were selected and introduced into a T2DM animal model to study their therapeutic efficacy.

Results: Among the tested strains, AP-32 and GL-104 had higher monosaccharide consumption rates and regulated the expression of monosaccharide transporters. Glucose transporter type-5 and Na-coupled glucose transporter mRNAs were downregulated in Caco-2 cells after AP-32 and GL-104 treatment, resulting in the modulation of intestinal hexose uptake. Animal studies revealed that diabetic mice treated with AP-32, GL-104, or both showed significantly decreased fasting blood glucose levels, improved glucose tolerance and blood lipid profiles, and attenuated diabetes-mediated liver and kidney injury.

Conclusion: Our data elucidate a novel role for probiotics in glycemic regulation in the host. AP-32 and GL-104 directly reduce monosaccharide transporter expression in gut cells and have potential as therapeutic probiotics for patients with T2DM.
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http://dx.doi.org/10.1136/bmjdrc-2019-001028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202753PMC
April 2020

Association between keratoconus and the risk of adolescent- or adult-onset atopic dermatitis.

Allergy 2020 11 5;75(11):2946-2948. Epub 2020 May 5.

Graduate Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan, Taiwan.

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http://dx.doi.org/10.1111/all.14320DOI Listing
November 2020

Joining Illumina paired-end reads for classifying phylogenetic marker sequences.

BMC Bioinformatics 2020 Mar 14;21(1):105. Epub 2020 Mar 14.

Molecular Diagnostic Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan.

Background: Illumina sequencing of a marker gene is popular in metagenomic studies. However, Illumina paired-end (PE) reads sometimes cannot be merged into single reads for subsequent analysis. When mergeable PE reads are limited, one can simply use only first reads for taxonomy annotation, but that wastes information in the second reads. Presumably, including second reads should improve taxonomy annotation. However, a rigorous investigation of how best to do this and how much can be gained has not been reported.

Results: We evaluated two methods of joining as opposed to merging PE reads into single reads for taxonomy annotation using simulated data with sequencing errors. Our rigorous evaluation involved several top classifiers (RDP classifier, SINTAX, and two alignment-based methods) and realistic benchmark datasets. For most classifiers, read joining ameliorated the impact of sequencing errors and improved the accuracy of taxonomy predictions. For alignment-based top-hit classifiers, rearranging the reference sequences is recommended to avoid improper alignments of joined reads. For word-counting classifiers, joined reads could be compared to the original reference for classification. We also applied read joining to our own real MiSeq PE data of nasal microbiota of asthmatic children. Before joining, trimming low quality bases was necessary for optimizing taxonomy annotation and sequence clustering. We then showed that read joining increased the amount of effective data for taxonomy annotation. Using these joined trimmed reads, we were able to identify two promising bacterial genera that might be associated with asthma exacerbation.

Conclusions: When mergeable PE reads are limited, joining them into single reads for taxonomy annotation is always recommended. Reference sequences may need to be rearranged accordingly depending on the classifier. Read joining also relaxes the constraint on primer selection, and thus may unleash the full capacity of Illumina PE data for taxonomy annotation. Our work provides guidance for fully utilizing PE data of a marker gene when mergeable reads are limited.
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http://dx.doi.org/10.1186/s12859-020-3445-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071698PMC
March 2020

Goat Milk Consumption Enhances Innate and Adaptive Immunities and Alleviates Allergen-Induced Airway Inflammation in Offspring Mice.

Front Immunol 2020 18;11:184. Epub 2020 Feb 18.

Center for Allergy and Clinical Immunology Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Goat milk (GM), as compared to cow milk (CM), is easier for humans to digest. It also has antioxidant and anti-inflammatory effects and can improve minor digestive disorders and prevent allergic diseases in infants. It is unclear whether GM consumed in pregnant mothers has any protective effects on allergic diseases in infants. In this experimental study with mice, we found GM feeding enhanced immunoglobulin production, antigen-specific (ovalbumin, OVA) immune responses, and phagocytosis activity. The GM-fed mice had an increasing proportion of CD3 T lymphocytes in the spleen. Splenocytes isolated from these animals also showed significantly increased production of cytokines IFN-γ and IL-10. More importantly, GM feeding during pregnancy and lactation periods can confer protective activity onto offspring by alleviating the airway inflammation of allergic asthma induced by mite allergens. There was a remarkably different composition of gut microbiota between offspring of pregnant mice fed with water or with milk (GM or CM). There was a greater proportion of beneficial bacterial species, such as , and in the gut microbiota of offspring from GM- or CM-fed pregnant mice compared to the offspring of water-fed pregnant mice. These results suggested that improving the nutrition of pregnant mice can promote immunological maturation and colonization of gut microbiota in offspring. This mother-to-child biological action may provide a protective effect on atopy development and alleviate allergen-induced airway inflammation in offspring.
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http://dx.doi.org/10.3389/fimmu.2020.00184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040033PMC
February 2021

White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases.

Asia Pac Allergy 2020 Jan 7;10(1):e11. Epub 2020 Feb 7.

Department of Pediatrics, Hanyang University Guri Hospital, Hanyang University College of Medicine, Seoul, Korea.

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level.
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http://dx.doi.org/10.5415/apallergy.2020.10.e11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016319PMC
January 2020

Drug hypersensitivity reactions in Asia: regional issues and challenges.

Asia Pac Allergy 2020 Jan 30;10(1):e8. Epub 2020 Jan 30.

Department of Pediatrics, Nippon Medical School, Tokyo, Japan.

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.
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http://dx.doi.org/10.5415/apallergy.2020.10.e8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016324PMC
January 2020

Toward personalization of asthma treatment according to trigger factors.

J Allergy Clin Immunol 2020 06 18;145(6):1529-1534. Epub 2020 Feb 18.

Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Womenś and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.
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http://dx.doi.org/10.1016/j.jaci.2020.02.001DOI Listing
June 2020

Subcutaneous injection of recombinant heat shock protein 70 ameliorates atopic dermatitis skin lesions in a mouse model.

Kaohsiung J Med Sci 2020 Mar 6;36(3):186-195. Epub 2020 Jan 6.

Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua County, Taiwan.

Atopic dermatitis (AD) is a chronic inflammatory skin disease and sometimes is a tough challenge for physicians. We previously reported that in Th2 environment, the production and secretion of thymic stromal lymphopoietin (TSLP) from human keratinocytes was inhibited by recombinant heat shock protein 70 (rHSP70). The present study assessed the therapeutic effectiveness of rHSP70 in a mouse model of AD. An experimental model of AD was reproduced by systemic sensitization and local epicutaneous challenge with ovalbumin (OVA). Treatment of rHSP70 was performed by subcutaneous administration. The levels of OVA-specific IgE, as well as cytokines, were detected by ELISA. Skin samples from patch areas were also taken for histologic examination. Injection of rHSP70 improved the histologic picture by reducing the thickness of epidermis and allergic inflammation. Skin sonography revealed rHSP70 ameliorated skin remodeling. rHSP70 also significantly decreased the protein expression of TSLP of skin from patch areas. Furthermore, in ex vivo studies also showed group of rHSP70 treatment decreased IL-13, RANTES, MIP-1β and increased IFN-γ secreted from splenocytes stimulated with OVA. The rHSP70 intervention in the mouse model of AD reduced the skin expression of TSLP and attenuated the clinical appearance of OVA-induced AD mice. The effect was achieved by suppressed Th2 immune response in injected skin tissue and enhanced systemic Th1 immune response. These results suggest that rHSP70 have potential as a promising protein for the treatment of AD.
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http://dx.doi.org/10.1002/kjm2.12163DOI Listing
March 2020

Vitamin D plasma concentration and vitamin D receptor genetic variants confer risk of asthma: A comparison study of Taiwanese and Mongolian populations.

World Allergy Organ J 2019 Nov 1;12(11):100076. Epub 2019 Nov 1.

Allergy and Clinical Immunology Research (ACIR) Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Background: Recent reports have suggested that lower vitamin D serum levels are associated with susceptibility to and severity of asthma in different white populations, which may be due to a lack of sunlight exposure, genetic polymorphism of vitamin D pathway genes, and dietary intake. We investigated the associations between vitamin D concentration, genetic polymorphism of the vitamin D receptor (VDR), and asthma traits in Mongolian and Taiwanese populations that inhabited two different geographical areas.

Methods: In total, 328 Han Taiwanese subjects and 381 Mongolian subjects were enrolled, and their vitamin D serum levels assayed. Genomic DNA of 178 Han Taiwanese subjects and 90 Mongolian subjects was obtained from blood samples. Single-nucleotide polymorphisms (SNPs) of VDR, (rs7975232), (rs731236), (rs1544410) and (rs2228570), were selected for genotyping. Logistic regression analyses were performed to detect an association between allergic asthma status and the interaction of the VDR SNP and serum vitamin D concentration in the case-control samples.

Results: We observed a significantly lower vitamin D level in the Mongolian subjects as compared with the Taiwanese population. In particular, in the population under 14 years of age, the serum vitamin D level was significantly higher in the Taiwanese population, in both non-asthmatic and asthmatic subjects, than in the Mongolian non-asthmatic and asthmatic subjects, respectively ( < 0.01). Moreover, the vitamin D level in the asthmatic children was significantly lower than that in the non-asthmatic children in both the Taiwanese and Mongolian populations (P < 0.01, respectively). Furthermore, we found that the rs2228570 genotype (OR, 3.763) of the VDR SNP and the vitamin D concentration (lower than 40 ng/ml, OR: 38.938) both contribute to increased susceptibility to bronchial asthma.

Conclusion: Our results demonstrated an association between vitamin D concentration and the risk of asthma in two populations of differing ethnicity living in different geographical areas. This information implies a potential role of vitamin D in the prevention and treatment of asthma worldwide.
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http://dx.doi.org/10.1016/j.waojou.2019.100076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838943PMC
November 2019

Actions needed for "Allergy in Asia-Pacific".

Authors:
Jiu-Yao Wang

Asia Pac Allergy 2019 Jul 29;9(3):e27. Epub 2019 Jul 29.

Allergy and Clinical Immunology Research Center, Division of Allergy and Clinical Immunology, Department of Pediatrics, National Cheng Kung University College of Medicine, Tainan 704, Taiwan.

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http://dx.doi.org/10.5415/apallergy.2019.9.e27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676059PMC
July 2019

Is asthma a protective factor for dengue fever? In vitro experiment and nationwide population-based cohort analysis.

Allergol Int 2019 Oct 24;68(4):486-493. Epub 2019 Jun 24.

Department of Pediatrics, Chang Gung Memorial Hospital - Kaohsiung Medical Centre, Kaohsiung, Taiwan.

Background: Dengue fever (DF) is the most rapidly spreading mosquito-borne viral disease. Practical vaccines or specific therapeutics are still expected. Environmental factors and genetic factors affect the susceptibility of Dengue virus (DV) infection. Asthma is a common allergic disease, with house dust mites (HDMs) being the most important allergens. Asthmatic patients are susceptible to several microorganism infections.

Methods: A nationwide population-based cohort analysis was designed to assess whether to determine whether asthma can be a risk factor for DF.

Results: Unexpectedly, our data from a nationwide population-based cohort revealed asthmatic patients are at a decreased risk of DF. Compared to patients without asthma, the hazard ratio (HR) for DF in patients with asthma was 0.166 (95% CI: 0.118-0.233) after adjustment for possible confounding factors. In the age stratification, the adjusted HR for DF in young adult patients with asthma was 0.063. Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) of dendritic cells (DCs) is an important entry for DV. Through another in vitro experiment, we found that HDM can diminish surface expression of DC-SIGN in monocyte-derived DCs and further decrease the cellular entry of DV.

Conclusions: Decreased DC-SIGN expression in DCs of allergic asthmatic patient may be one of many factors for them to be protected against DF. This could implicate the potential for DC-SIGN modulation as a candidate target for designing therapeutic strategies for DF.
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http://dx.doi.org/10.1016/j.alit.2019.06.001DOI Listing
October 2019

Blocking IL-19 Signaling Ameliorates Allergen-Induced Airway Inflammation.

Front Immunol 2019 30;10:968. Epub 2019 Apr 30.

Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Asthma is a chronic inflammatory disease of the airway. Its major symptoms are reversible breathing problems causing airway narrowing and obstruction. IL-19 is a member of the IL-10 family cytokines. We previously showed that IL-19 induces T-helper 2 (Th2) cytokines and that asthma patients had higher serum IL-19 levels. To further examine whether inhibiting IL-19 and its receptor (IL-20R1) protected rodents against asthma, we used (; house dust mites) to induce chronic airway inflammation in wild-type C57BL/6 and IL-20R1-deficient mice and then analyzed the effect of the IL-20R1 deficiency on the pathogenesis of asthma. We also examined whether inhibiting IL-19 and IL-20R1 ameliorated -induced chronic asthma. induced IL-19 in lung airway epithelial cells, type 2 alveolar cells, and alveolar macrophages. An IL-20R1 deficiency abolished IL-19-induced Th2 cell differentiation . Th2 cytokine expression, immune cell infiltration in the bronchoalveolar lavage, airway hyperresponsiveness (AHR), and bronchial wall thickening were lower in -challenged IL-20R1-deficient mice. Anti-IL-20R1 monoclonal antibody (mAb) 51D and IL-19 polyclonal antibody (pAb) both ameliorated -induced AHR, lung immune cell infiltration, bronchial wall thickening, and Th2 cytokine expression. Moreover, we confirmed that anti-IL-19 mAb (1BB1) attenuated lung inflammation in a rat ovalbumin-induced asthma model. This is the first report to show that inhibition of IL-19 by targeting IL-19 or IL-20R1 protected rodents from allergic lung inflammation. Our study suggests that targeting IL-19 signaling might be a novel therapeutic strategy for treating allergic asthma.
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http://dx.doi.org/10.3389/fimmu.2019.00968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503049PMC
September 2020

High correlation between human rhinovirus type C and children with asthma exacerbations in Taiwan.

J Microbiol Immunol Infect 2020 Aug 15;53(4):561-568. Epub 2018 Dec 15.

School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan; School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan; Department of Pediatrics, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.

Background/purposes: Human rhinovirus type C (HRV-C) has been associated with asthma exacerbation (AE) in children in several countries. However, in Taiwan the association between HRV, especially HRV-C, and AE in children has yet to be elucidated. We sought to investigate the prevalence of respiratory viruses in children with acute lower respiratory tract infection (ALRTI) in Taiwan and the association between different types of HRV and AE in children.

Methods: This prospective study was conducted from 2011 to 2013, and enrolled children with ALRTI, including an asthma exacerbation group (AE; n = 28) and a Non-asthma group (n = 66). Viruses were detected by culture, reverse transcription-polymerase chain reaction, and molecular sequencing of nasopharyngeal swabs.

Results: The prevalence of identified respiratory viruses was 78.6% in the AE group and 65.2% in the Non-asthma group. The prevalence rates of HRV and HRV-C were significantly higher in the AE group than in the Non-asthma group (67.9% vs. 33.3% in HRV, p = 0.002; and 50% vs. 15.2% in HRV-C, p < 0.001). Among the children with HRV, the prevalence of HRV-C (68.4%) was higher than that of the other types of HRV (31.6%, including HRV-A 26.3%, and HRV-B 5.3%) in the AE group but not in the Non-asthma group (40.9% vs. 59.1%).

Conclusions: HRV is the most predominant viral infection responsible for pediatric AE in Taiwan, and HRV-C is responsible for more of these exacerbations than HRV-A or HRV-B.
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http://dx.doi.org/10.1016/j.jmii.2018.12.001DOI Listing
August 2020

Warm up, cool down, and tearing apart in NK cell memory.

Cell Mol Immunol 2018 12 28;15(12):1095-1097. Epub 2018 Nov 28.

Department of Pediatrics, Center for Allergy and Clinical Immunology Research, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan, China.

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http://dx.doi.org/10.1038/s41423-018-0188-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269542PMC
December 2018

Increasing trends of anaphylaxis-related events: an analysis of anaphylaxis using nationwide data in Taiwan, 2001-2013.

World Allergy Organ J 2018 10;11(1):23. Epub 2018 Oct 10.

6Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli 350 Taiwan.

Background: Anaphylaxis is a severe, potentially fatal, and systemic allergic reaction. Previous studies document increasing trends in incidence rates of anaphylaxis-related events in Western countries, yet little is known about the incidence and trend of anaphylaxis in Asia. In this study, we aimed to determine time trends in incidence rates of anaphylaxis-related events in Taiwan from 2001 through 2013.

Methods: We utilized medical claims data from the National Health Insurance Research Databases in Taiwan. We identified anaphylaxis-related events (ICD-9-CM-codes: 995.0, 995.60-995.69, 999.41-999.42, and 999.49) and calculated incidence rates. Poisson regression models were applied to examine trends and incidence rates.

Results: A total of 2496 patients (mean age, 45.11 years; 56% male) with first-time anaphylaxis were identified during 34,430,000 person-years of observation time. The overall incidence of anaphylaxis was 7.25 (95% confidence interval (CI) = 6.97-7.53) per 100,000 person-years, increasing from 4.79 in 2001 to 8.20 in 2013, with an incidence rate ratio (IRR) of 1.05 (95%CI = 1.04-1.06). Over the 13-year period, the increasing trends were found in incident diagnosis of anaphylaxis-related outpatient or emergency department visits (IRR = 1.06, 95%CI = 1.05-1.08) and admissions to intensive care units (IRR = 1.06, 95%CI = 1.03-1.10), whereas the trends in incidence of anaphylaxis-related hospitalizations remained steady. The proportion of patients requiring hospitalizations among all patients with anaphylaxis ( = 0.01), as well as the proportion requiring intensive care treatment among patients who were hospitalized ( = 0.01), both increased with age.

Conclusion: The incidence rate of anaphylaxis in Taiwan has increased at an average rate of 5% annually since 2001, paralleling the rising trends in several Western countries.
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http://dx.doi.org/10.1186/s40413-018-0202-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178262PMC
October 2018