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1.
J Formos Med Assoc ; 121(11): 2161-2171, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35346540

ABSTRACT

BACKGROUND/PURPOSE: This study examined the prevalence and related factors of multiple (two or three) types of harassment victimization, including school bullying, cyberbullying, and teacher harassment, and their cumulative effects on depression, anxiety, self-esteem, and suicidality in adolescents with autism spectrum disorder (ASD) but without intellectual disability. METHODS: A total of 219 adolescents with ASD but without intellectual disability and their parents participated in this study. Their experiences of school bullying, cyberbullying, and teacher harassment were evaluated. The related factors of multiple types of harassment victimization, including demographic characteristics, socio-communicative skills, comorbid attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) symptoms, were examined. Moreover, the effects of multiple types of harassment victimization on depression, anxiety, self-esteem, and suicidality were examined. RESULTS: In total, 20.54% of participants were victims of multiple types of harassment. Hyperactivity or impulsivity and ODD symptoms were positively associated with multiple types of harassment victimization. Adolescents with ASD who experienced multiple types of harassment victimization had higher severities of depression and anxiety and were more likely to have suicidality than nonvictims and those who experienced only one type of harassment victimization. CONCLUSION: Experiencing more than one type of harassment victimization was significantly associated with the development of mental health problems in adolescents with ASD. ODD and hyperactivity/impulsivity symptoms predicted the risk of experiencing multiple types of harassment.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Bullying , Crime Victims , Intellectual Disability , Adolescent , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/psychology , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/psychology , Bullying/psychology , Crime Victims/psychology , Humans , Mental Health
2.
Mol Cell ; 48(5): 747-59, 2012 Dec 14.
Article in English | MEDLINE | ID: mdl-23123197

ABSTRACT

NPGPx is a member of the glutathione peroxidase (GPx) family; however, it lacks GPx enzymatic activity due to the absence of a critical selenocysteine residue, rendering its function an enigma. Here, we show that NPGPx is a newly identified stress sensor that transmits oxidative stress signals by forming the disulfide bond between its Cys57 and Cys86 residues. This oxidized form of NPGPx binds to glucose-regulated protein (GRP)78 and forms covalent bonding intermediates between Cys86 of NPGPx and Cys41/Cys420 of GRP78. Subsequently, the formation of the disulfide bond between Cys41 and Cys420 of GRP78 enhances its chaperone activity. NPGPx-deficient cells display increased reactive oxygen species, accumulated misfolded proteins, and impaired GRP78 chaperone activity. Complete loss of NPGPx in animals causes systemic oxidative stress, increases carcinogenesis, and shortens life span. These results suggest that NPGPx is essential for releasing excessive ER stress by enhancing GRP78 chaperone activity to maintain physiological homeostasis.


Subject(s)
Carrier Proteins/metabolism , Endoplasmic Reticulum Stress , Heat-Shock Proteins/metabolism , Oxidative Stress , Peroxidases/metabolism , Proteostasis Deficiencies/enzymology , Signal Transduction , Animals , Carrier Proteins/genetics , Cell Line, Tumor , Cell Proliferation , Cell Survival , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Cysteine , DNA Damage , Disulfides/metabolism , Dose-Response Relationship, Drug , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress/drug effects , Endoplasmic Reticulum Stress/genetics , Fibroblasts/enzymology , Fibroblasts/pathology , Glutathione Peroxidase , Heat-Shock Proteins/genetics , Homeostasis , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Mutagenesis, Site-Directed , Mutation , Oxidants/pharmacology , Oxidation-Reduction , Oxidative Stress/drug effects , Oxidative Stress/genetics , Peroxidases/genetics , Protein Binding , Protein Folding , Proteostasis Deficiencies/genetics , Proteostasis Deficiencies/pathology , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , Time Factors , Transfection
3.
BMC Gastroenterol ; 19(1): 33, 2019 Feb 19.
Article in English | MEDLINE | ID: mdl-30782138

ABSTRACT

BACKGROUND: The prevalence rate of reflux esophagitis (RE) in Asia, including Taiwan, has increased dramatically in recent years. However, few studies have discussed on its relationship with metabolic syndrome (MetS). This study aimed to evaluate the correlation between RE and MetS and its components. METHODS: We conducted a cross-sectional study during 2013 to 2014 in Taiwan. A total of 4895 subjects who completed upper gastrointestinal endoscopy at the Health Examination Center of Changhua Christian Hospital were enrolled. RE was defined according to the upper gastrointestinal endoscopic findings and MetS was defined according to the Taiwanese criteria. Univariate and multivariate logistic regression analyses were applied to calculate odds ratios and 95% confidence intervals for each variable to assess the associated features for RE. We analyzed the relationship between the number of MetS components and the severity of RE using the chi-square test for trend. RESULTS: The prevalence rates of MetS and RE were respectively 28.5 and 59.6%. According to univariate logistic regression analysis, MetS was significantly associated with RE and remained a positive association in multivariate logistic regression analysis (adjusted ORß = 1.251; 95% CI = 1.071-1.462; p = 0.005). Furthermore, among the five MetS components, elevated blood pressure (adjusted ORγ = 1.163; 95% CI = 1.023-1.323; p = 0.021), abdominal obesity (adjusted ORγ = 1.173; 95% CI = 1.020-1.349; p = 0.026) and hyperglycemia (adjusted ORγ = 1.306; 95% CI = 1.142-1.495; p < 0.001) were positively associated with the presence of RE. A weak association was also found between elevated triglycerides and RE after adjusting for age and gender (adjusted ORα = 1.171; 95% CI = 1.022-1.343; p = 0.023). Reduced high-density lipoprotein cholesterol showed no significant difference between groups with and without RE. Older age (≥65 years), male gender, higher body mass index, higher uric acid, smoking, alcohol drinking, and hiatal hernia were found to be significant associated factors for RE. In addition, a dose-response relation between the number of MetS components and the presence of RE was demonstrated in the multivariate analysis. Furthermore, we performed a trend analysis and found the severity of RE got worse as the number of MetS components increased (p < 0.001). CONCLUSION: This study suggests that MetS is significantly related to the presence and the severity of RE.


Subject(s)
Esophagitis, Peptic/epidemiology , Metabolic Syndrome/epidemiology , Adult , Aged , Comorbidity , Cross-Sectional Studies , Esophagitis, Peptic/complications , Female , Humans , Hyperglycemia/complications , Hypertension/complications , Male , Metabolic Syndrome/complications , Middle Aged , Obesity, Abdominal/complications , Prevalence , Retrospective Studies , Severity of Illness Index , Taiwan/epidemiology
4.
Int J Mol Sci ; 19(2)2018 Jan 24.
Article in English | MEDLINE | ID: mdl-29364155

ABSTRACT

Candida albicans is the most commonly encountered human fungal pathogen, and it is traditionally treated with antimicrobial chemical agents. The antimicrobial effect of these agents is largely weakened by drug resistance and biofilm-associated virulence. Enhancement of the antimicrobial activity of existing agents is needed for effective candidiasis treatment. Our aim was to develop a therapy that combined biofilm disruption with existing antimicrobial agents. Photodynamic therapy (PDT) utilizing curcumin and blue light was tested as an independent therapy and in combination with fluconazole treatment. Viability assays and morphology analysis were used to assess the effectiveness of C. albicans treatment. Results showed that fluconazole treatment decreased the viability of planktonic C. albicans, but the decrease was not as pronounced in adherent C. albicans because its biofilm form was markedly more resistant to the antimicrobiotic. PDT effectively eradicated C. albicans biofilms, and when combined with fluconazole, PDT significantly inhibited C. albicans to a greater extent. This study suggests that the addition of PDT to fluconazole to treat C. albicans infection enhances its effectiveness and can potentially be used clinically.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Candida albicans/radiation effects , Photochemotherapy , Antifungal Agents/therapeutic use , Biofilms/drug effects , Candida albicans/growth & development , Candidiasis/microbiology , Candidiasis/therapy , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Membrane/radiation effects , Combined Modality Therapy , Curcumin/pharmacology , Curcumin/therapeutic use , Fluconazole/pharmacology , Fluconazole/therapeutic use , Free Radicals/metabolism , Humans , Microbial Viability/drug effects , Microbial Viability/radiation effects , Singlet Oxygen/metabolism
5.
J Pathol ; 236(3): 337-47, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25775999

ABSTRACT

Although hepatitis B virus (HBV) has been established to cause hepatocellular carcinoma (HCC), the exact mechanism remains to be clarified. Type II ground glass hepatocytes (GGHs) harbouring the HBV pre-S2 mutant large surface protein (LHBS) have been recognized as a morphologically distinct hallmark of HCC in the advanced stages of chronic HBV infection. Considering its preneoplastic nature, we hypothesized that type II GGH may exhibit high genomic instability, which is important for the carcinogenic process in chronic HBV carriers. In this study we found that pre-S2 mutant LHBS directly interacted with importin α1, the key factor that recognizes cargos undergoing nuclear transportation mediated by the importin α/ß-associated nuclear pore complex (NPC). By interacting with importin α1, which inhibits its function as an NPC factor, pre-S2 mutant LHBS blocked nuclear transport of an essential DNA repair and recombination factor, Nijmegen breakage syndrome 1 (NBS1), upon DNA damage, thereby delaying the formation of nuclear foci at the sites of DNA double-strand breaks (DSBs). Pre-S2 mutant LHBS was also found to block NBS1-mediated homologous recombination repair and induce multi-nucleation of cells. In addition, pre-S2 mutant LHBS transgenic mice showed genomic instability, indicated by increased global gene copy number variations (CNVs), which were significantly higher than those in hepatitis B virus X mice, indicating that pre-S2 mutant LHBS is the major viral oncoprotein inducing genomic instability in HBV-infected hepatocytes. Consistently, the human type II GGHs in HCC patients exhibited increased DNA DSBs representing significant genomic instability. In conclusion, type II GGHs harbouring HBV pre-S2 mutant oncoprotein represent a high-risk marker for the loss of genome integrity in chronic HBV carriers and explain the complex chromosome changes in HCCs. Mouse array CGH raw data: GEO Accession No. GSE61378 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61378).


Subject(s)
Carcinoma, Hepatocellular/genetics , Cell Transformation, Viral/genetics , Hepatitis B Surface Antigens/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/genetics , Liver Neoplasms/genetics , Protein Precursors/genetics , Animals , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Cell Line, Tumor , Comparative Genomic Hybridization , DNA Breaks, Double-Stranded , DNA Copy Number Variations , DNA Damage , DNA Repair , Female , Genomic Instability , Hepatitis B Surface Antigens/metabolism , Hepatitis B virus/metabolism , Hepatitis B, Chronic/metabolism , Hepatitis B, Chronic/pathology , Hepatitis B, Chronic/virology , Hepatocytes/metabolism , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/virology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mutation , Protein Precursors/metabolism , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism
6.
Soft Matter ; 10(47): 9568-76, 2014 Dec 21.
Article in English | MEDLINE | ID: mdl-25357089

ABSTRACT

We report the versatility of polyion complex (PIC) micelles for the preparation of shell and core cross-linked (SCL and CCL) micelles with their surface properties determined by the constituent polymer composition and cross-linking agent. The negatively and positively charged PIC micelles with their molecular structure and properties depending on the mixing weight percentage and polymer molecular weight were first prepared by mixing the negatively and positively charged polyions, poly(acrylic acid) (PAA) and poly(L-lysine) (PLL). The feasibility of preparing SCL micelles was demonstrated by cross-linking the shell of the negatively and positively charged micelles using cystamine and genipin, respectively. The core of the micelles can be cross-linked by silica deposition to stabilize the assemblies. The shell and/or core cross-linked micelles exhibited excellent colloid stability upon changing solution pH. The drug release from the drug-loaded SCL micelles revealed that the controllable permeability of the SCL micelles can be achieved by tuning the cross-linking degree and the SCL micelles exhibited noticeable pH-responsive behavior with accelerated release under acidic conditions. With the versatility of cross-linking strategies, it is possible to prepare a variety of SCL and CCL micelles from PIC micelles.


Subject(s)
Acrylic Resins/chemistry , Antibiotics, Antineoplastic/chemistry , Doxorubicin/chemistry , Drug Carriers/chemistry , Models, Chemical , Polylysine/analogs & derivatives , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/analysis , Cross-Linking Reagents/chemistry , Cystamine/chemistry , Doxorubicin/administration & dosage , Doxorubicin/analysis , Drug Carriers/administration & dosage , Drug Carriers/analysis , Drug Compounding , Drug Stability , Feasibility Studies , Hydrogen-Ion Concentration , Iridoids/chemistry , Kinetics , Materials Testing , Micelles , Molecular Weight , Permeability , Polylysine/chemistry , Solubility , Surface Properties
7.
Cancer Res ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38657118

ABSTRACT

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion. A better understanding of the mechanisms by which this oncogenic transcriptional regulator drives cancer growth is needed to help identify potential therapeutic targets. Here, we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models, identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology. ASPSCR1::TFE3 directly interacted with key epigenetic regulators at enhancers and promoters to support ASPS-associated transcription. Among the effector programs driven by ASPSCR1::TFE3, cell proliferation was driven by high levels of cyclin D1 expression. Disruption of cyclin D1/CDK4 signaling led to loss of ASPS proliferative capacity, and combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts. These results define the ASPS oncogenic program, reveal mechanisms by which ASPSCR1::TFE3 controls tumor biology, and identify a strategy for therapeutically targeting tumor cell-intrinsic vulnerabilities.

8.
Carcinogenesis ; 34(2): 475-85, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23172669

ABSTRACT

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S(2) mutant large HBV surface antigen (LHBS) in type II ground glass hepatocytes (GGHs) has been recognized as an emerging viral oncoprotein; it directly interacts with the c-Jun activation domain-binding protein 1 (JAB1) and subsequently causes hyperphosphorylation of the tumor-suppressor retinoblastoma and, consequently, leads to disturbed cell cycle progression. The interaction of the pre-S(2) mutant LHBS with JAB1 could provide a potential target for chemoprevention. In this study, we found that the preneoplastic type II GGHs showed a significant decrease of the cyclin-dependent kinase inhibitor p27(Kip1), which serves as a marker for pre-S(2) mutant-JAB1 complex formation. The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) elevated expression of the tumor-suppressor thioredoxin-binding protein 2 (TBP2), which subsequently enhanced the JAB1-TBP2 interaction and abolished the pre-S(2) mutant LHBS-induced degradation of p27(Kip1), which, in turn, recovered the normal cell cycle checkpoint. The pre-S(2) mutant LHBS-induced pro-oncogenic effects: increased cell proliferation, nuclear/cytoplasmic ratio and proliferating cell nuclear antigen expression, were all greatly ameliorated after SAHA treatments, which suggested SAHA as a promising chemopreventive agent for the pre-S(2) mutant oncoprotein-induced HCC. In conclusion, this study provides the mechanism of histone deacetylase (HDAC) inhibitor in preventing the pre-S(2) mutant-induced oncogenic phenotype. The HDAC inhibitor SAHA is therefore a potential chemopreventive agent for high-risk chronic HBV patients who may develop HCC.


Subject(s)
Carcinoma, Hepatocellular/prevention & control , Cell Proliferation/drug effects , Hepatitis B Surface Antigens/metabolism , Hepatitis B, Chronic/prevention & control , Hydroxamic Acids/pharmacology , Liver Neoplasms/prevention & control , Mutation/genetics , Protein Precursors/metabolism , Animals , Apoptosis/drug effects , Blotting, Western , COP9 Signalosome Complex , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/metabolism , Cell Cycle/drug effects , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Cytoplasm/drug effects , Cytoplasm/metabolism , Female , Fluorescent Antibody Technique , Hepatitis B Surface Antigens/genetics , Hepatitis B virus/drug effects , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/virology , Hepatocytes/cytology , Hepatocytes/drug effects , Hepatocytes/metabolism , Histone Deacetylase Inhibitors/pharmacology , Humans , Immunoenzyme Techniques , Immunoprecipitation , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Liver Neoplasms/etiology , Liver Neoplasms/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mutant Proteins/genetics , Mutant Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Peptide Hydrolases/genetics , Peptide Hydrolases/metabolism , Protein Precursors/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , TATA Box Binding Protein-Like Proteins/genetics , TATA Box Binding Protein-Like Proteins/metabolism , Two-Hybrid System Techniques , Vorinostat
9.
Anal Chim Acta ; 1272: 341492, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37355321

ABSTRACT

Beta-agonists are potent bronchodilators approved for the treatment of asthma and tocolysis. However, they have been extensively misused as feed additives in the veterinary field to improve feed efficiency. The concern over their potential hazard to health has come to the fore again. In this study, a novel vinylene-based covalent organic framework (V-COF-1) with a two-dimensional structure was developed. The structure shows good tolerance in a variety of mediums, which can be attributed to the low polarity linkage. The high specific surface area and variable interaction with analytes accelerate the extraction time. Furthermore, the swelling resulting from the formation of hydrogen bonds by the protic solvent intercalation with the triazine group also improves the adsorption efficiency. Finally, due to its great reusability, it is economical material in sample preparation application. The V-COF-1 based µ-dSPE approach was coupled with UHPLC-MS/MS to develop a highly sensitive and selective method. The linearity of the method ranged from 0.05 to 20 ng g-1 with a correlation coefficient (R2) higher than 0.9958, and the limits of detection and quantification fell in the ranges of 0.01-0.10 ng g-1 and 0.04-0.32 ng g-1. The proposed method has been successfully applied to determine beta-agonists in meat samples, and the results indicated good recovery of 82.2-116%. The intra-day and inter-day precision were less than 6.61%, indicating the potential for sustainable application in food analysis.


Subject(s)
Metal-Organic Frameworks , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Metal-Organic Frameworks/chemistry , Solid Phase Extraction/methods , Limit of Detection , Meat/analysis
10.
Talanta ; 263: 124733, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37247453

ABSTRACT

A novel sorbent Cu-S metal-organic framework (MOF) microrods was prepared for dispersive solid-phase extraction via microwave synthesis and used to determine 12 fluoroquinolones (FQs) in honey samples employing ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The best extraction efficiency was achieved by optimizing sample pH, sorbent quantity, eluent type/volume, and extraction and elution time. The proposed MOF exhibits advantages such as rapid synthesis time (20 min) and outstanding adsorption ability toward zwitterionic FQs. These advantages can be attributed to multiple interactions, including hydrogen bonding, π-π interaction, and hydrophobic interaction. The limits of detection of analytes were 0.005-0.045 ng g-1. Acceptable recoveries (79.3%-95.6%) were obtained under the optimal conditions. Precision (relative standard deviation, RSD) was <9.2%. These results demonstrate the utility of our sample preparation method and the high capacity of Cu-S MOF microrods for rapid and selective extraction of FQs from honey samples.


Subject(s)
Honey , Metal-Organic Frameworks , Fluoroquinolones/analysis , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Honey/analysis , Microwaves , Solid Phase Extraction/methods
11.
J Autism Dev Disord ; 53(2): 648-655, 2023 Feb.
Article in English | MEDLINE | ID: mdl-33474660

ABSTRACT

Little research has examined burn injury in the pediatric population with autism spectrum disorder (ASD). We used data from Taiwan's National Health Insurance Research Database to identify 15,844 participants aged <18 years with ASD and 130,860 participants without ASD. Our results revealed that the hazard ratios differed across three age ranges. The ASD group had a lower risk of burn injury than the non-ASD group when they were less than 6 years of age, a higher risk from 6 years to 12 years of age, and no difference when they were older than 12 years of age. More research is required to study the characteristics and causes of burn injury in the pediatric population with ASD.


Subject(s)
Autism Spectrum Disorder , Burns , Child , Humans , Adolescent , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/etiology , Risk , Burns/epidemiology , Burns/complications , Proportional Hazards Models , Databases, Factual
12.
Article in English | MEDLINE | ID: mdl-36834428

ABSTRACT

School bullying and cyberbullying victimization and perpetration are prevalent in adolescents with autism spectrum disorder (AASD). However, the levels of adolescent-caregiver agreement regarding the bullying involvement of AASD and the factors associated with these levels remain to be evaluated. In the present study, we evaluated the levels of adolescent-caregiver agreement on the school bullying and cyberbullying involvement experiences of AASD and the factors associated with the levels of agreement. This study included 219 dyads of AASD and their caregivers. The school bullying and cyberbullying involvement experiences of the participating AASD were assessed using the School Bullying Experience Questionnaire and the Cyberbullying Experiences Questionnaire, respectively. Attention-deficit/hyperactivity disorder, oppositional defiant disorder (ODD), depressive and anxiety symptoms, and autistic social impairment were also assessed. AASD and their caregivers had poor to fair levels of agreement regarding the school bullying and cyberbullying victimization and perpetration experiences of AASD. Severe inattention, hyperactivity-impulsivity, ODD, depressive and anxiety symptoms, and autistic social impairment were associated with high levels of adolescent-caregiver agreement. When assessing the bullying involvement experiences of AASD, mental health professionals should obtain information from multiple sources. In addition, the factors influencing the levels of agreement should be considered.


Subject(s)
Autism Spectrum Disorder , Bullying , Crime Victims , Cyberbullying , Humans , Adolescent , Cyberbullying/psychology , Autism Spectrum Disorder/psychology , Caregivers , Bullying/psychology , Crime Victims/psychology , Schools
13.
Neuropsychiatr Dis Treat ; 18: 327-339, 2022.
Article in English | MEDLINE | ID: mdl-35210779

ABSTRACT

BACKGROUND: The Autism Diagnostic Interview-Revised (ADI-R) is an essential semi-structured diagnostic tool for autism spectrum disorder (ASD). This study aims to validate the Chinese version of the ADI-R in Taiwan. METHODS: The Chinese version of the ADI-R was translated and back-translated by professional translators and was approved by the original authors. A group of child psychiatrists and psychologists corrected medical terminology for the final version. Then, a total of 74 participants with ASD (male, 59, 79.73%) and 33 control participants without ASD (male, 16, 48.48%) were recruited. All participants were between 3 years 4 months to 41 years old (mean: 14.63 ± 7.93 years). Exploratory factor analysis (EFA) was used to measure the factor structure. RESULTS: Cronbach's α showed good to excellent internal consistency (0.78-0.98) over the three core symptom domains of the Chinese version of the ADI-R. Pearson's correlation analysis revealed very high test-retest reliability (Pearson's correlation coefficients ranging from 0.95 to 0.99). EFA supported three categories of factors. For correct diagnosis of ASD, the Chinese version of the ADI-R had high sensitivity (97.30%), specificity (100%), positive predictive value (PPV) (100%), and negative predictive value (NPV) (94.29%). All domains also showed excellent area under the curves (0.991-1), sensitivity (94.59-98.65%), specificity (96.97-100%), Youden index (94.59-98.65%), PPV (97.78-100%), NPV (89.19-100%), positive likelihood ratio (32.55-33.00%) and negative likelihood ratio (0.00-0.05) after statistical examination. CONCLUSION: The Chinese version of the ADI-R is a reliable and valid diagnostic tool for the diagnosis of ASD in Clinical settings in Taiwan.

14.
Cancers (Basel) ; 12(6)2020 Jun 12.
Article in English | MEDLINE | ID: mdl-32545657

ABSTRACT

Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. Methods: We used data from Taiwan's National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25-0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.

15.
J Biomed Sci ; 16: 84, 2009 Sep 15.
Article in English | MEDLINE | ID: mdl-19751529

ABSTRACT

BACKGROUND: Chronic hepatitis B virus (HBV) infection is an important cause of hepatocellular carcinoma (HCC) worldwide. The pre-S1 and -S2 mutant large HBV surface antigen (LHBS), in which the pre-S1 and -S2 regions of the LHBS gene are partially deleted, are highly associated with HBV-related HCC. METHODS: The pre-S region of the LHBS gene in two hundred and one HBV-positive serum samples was PCR-amplified and sequenced. A pre-S oligonucleotide gene chip was developed to efficiently detect pre-S deletions in chronic HBV carriers. Twenty serum samples from chronic HBV carriers were analyzed using the chip. RESULTS: The pre-S deletion rates were relatively low (7%) in the sera of patients with acute HBV infection. They gradually increased in periods of persistent HBV infection: pre-S mutation rates were 37% in chronic HBV carriers, and as high as 60% in HCC patients. The Pre-S Gene Chip offers a highly sensitive and specific method for pre-S deletion detection and is less expensive and more efficient (turnaround time 3 days) than DNA sequencing analysis. CONCLUSION: The pre-S1/2 mutants may emerge during the long-term persistence of the HBV genome in carriers and facilitate HCC development. Combined detection of pre-S mutations, other markers of HBV replication, and viral titers, offers a reliable predictive method for HCC risks in chronic HBV carriers.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , DNA Mutational Analysis/instrumentation , DNA, Viral/genetics , Hepatitis B Antigens/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Liver Neoplasms/epidemiology , Oligonucleotide Array Sequence Analysis , Viral Envelope Proteins/genetics , Carcinoma, Hepatocellular/etiology , DNA, Viral/blood , Hepatitis B virus/pathogenicity , Hepatitis B, Chronic/blood , Humans , Liver Neoplasms/etiology , Mutation , Polymerase Chain Reaction , Predictive Value of Tests , Risk , Sequence Deletion
16.
BMC Med Genomics ; 12(Suppl 8): 169, 2019 12 20.
Article in English | MEDLINE | ID: mdl-31856824

ABSTRACT

BACKGROUND: To facilitate the investigation of the pathogenic roles played by various immune cells in complex tissues such as tumors, a few computational methods for deconvoluting bulk gene expression profiles to predict cell composition have been created. However, available methods were usually developed along with a set of reference gene expression profiles consisting of imbalanced replicates across different cell types. Therefore, the objective of this study was to create a new deconvolution method equipped with a new set of reference gene expression profiles that incorporate more microarray replicates of the immune cells that have been frequently implicated in the poor prognosis of cancers, such as T helper cells, regulatory T cells and macrophage M1/M2 cells. METHODS: Our deconvolution method was developed by choosing ε-support vector regression (ε-SVR) as the core algorithm assigned with a loss function subject to the L1-norm penalty. To construct the reference gene expression signature matrix for regression, a subset of differentially expressed genes were chosen from 148 microarray-based gene expression profiles for 9 types of immune cells by using ANOVA and minimizing condition number. Agreement analyses including mean absolute percentage errors and Bland-Altman plots were carried out to compare the performances of our method and CIBERSORT. RESULTS: In silico cell mixtures, simulated bulk tissues, and real human samples with known immune-cell fractions were used as the test datasets for benchmarking. Our method outperformed CIBERSORT in the benchmarks using in silico breast tissue-immune cell mixtures in the proportions of 30:70 and 50:50, and in the benchmark using 164 human PBMC samples. Our results suggest that the performance of our method was at least comparable to that of a state-of-the-art tool, CIBERSORT. CONCLUSIONS: We developed a new cell composition deconvolution method and the implementation was entirely based on the publicly available R and Python packages. In addition, we compiled a new set of reference gene expression profiles, which might allow for a more robust prediction of the immune cell fractions from the expression profiles of cell mixtures. The source code of our method could be downloaded from https://github.com/holiday01/deconvolution-to-estimate-immune-cell-subsets.


Subject(s)
Computational Biology/methods , Gene Expression Profiling , Immune System/cytology , Computer Simulation , Humans , Leukocytes, Mononuclear/metabolism , Oligonucleotide Array Sequence Analysis , Support Vector Machine
17.
Pharmaceutics ; 11(1)2019 Jan 04.
Article in English | MEDLINE | ID: mdl-30621174

ABSTRACT

Antibiotic resistance has become a crisis. Candida tropicalis (C. tropicalis) is one of the most highly virulent and drug-resistant pathogens. An alternative antimicrobial therapy to eradicate C. tropicalis effectively, without the risk of developing drug-resistance, is needed. Photodynamic therapy (PDT) is an alternative therapy that does not carry the risk of undesired drug resistance. To target the pathogens and to enhance the cellular penetration of the applied photosensitizer, we fabricated cationic chitosan/tripolyphosphate nanoparticles to encapsulate phthalocyanine. Our strategy promotes the uptake of phthalocyanine four-fold. This enhanced PDT can effectively inhibit planktonic C. tropicalis, such that only ~20% of C. tropicalis in the test survived; but it has a limited ability to inhibit adherent C. tropicalis. Further tests with adherent C. tropicalis indicated that sequential treatment with PDT and flucytosine significantly eliminates pseudohyphae and yeast-like C. tropicalis cells. The cell viability is only ~10% after this sequential treatment. This study provides evidence of an effective therapy against drug resistant C. tropicalis, and this strategy can be potentially applied to other pathogens.

18.
Cancer Med ; 8(9): 4484-4496, 2019 08.
Article in English | MEDLINE | ID: mdl-31183993

ABSTRACT

OBJECTIVE: The association between antipsychotic use and gastric cancer risk remains unclear. Therefore, this study aimed to determine the association between antipsychotic exposure and the incidence of gastric cancer. METHODS: Using a nested case-control design, a total of 34 470 gastric cancer patients and 163 430 nongastric cancer controls were identified from Taiwan's National Health Insurance Research Database between 1 January 1997 and 31 December 2013. We analyzed the data using a conditional logistic regression model to adjust for possible confounding variables. RESULTS: Antipsychotic use was independently inversely associated with gastric cancer risk after controlling for potential confounding factors including income, urbanization, medications, physical and medical illness, aspirin use, nonsteroidal anti-inflammatory drug use and triple therapy. In addition, dose-dependent trends against gastric cancer risk were also shown with individual antipsychotic compounds including thioridazine, haloperidol, sulpiride, clozapine, olanzapine, quetiapine, amisulpride, and risperidone. A sensitivity analysis showed that second-generation antipsychotics had significant dose-dependent effects in reducing the risk of gastric cancer risk in patients with and without peptic ulcer disease. CONCLUSIONS: Antipsychotic use was inversely associated with gastric cancer risk, and dose-dependent effects against gastric cancer were also seen with several individual antipsychotic compounds.


Subject(s)
Antipsychotic Agents/therapeutic use , Stomach Neoplasms/epidemiology , Adult , Aged , Case-Control Studies , Databases, Factual , Dose-Response Relationship, Drug , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Taiwan/epidemiology , Young Adult
19.
Article in English | MEDLINE | ID: mdl-30925769

ABSTRACT

The aim of this study was to examine the prevalence of self-reported and parent-reported bullying victimization, perpetration, and victimization-perpetration and the associations of autistic social impairment and attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms with bullying involvement in adolescents with high functioning autism spectrum disorder (ASD). A total of 219 adolescents with high functioning ASD participated in this study. The associations of sociodemographic characteristics, parent-reported autistic social impairment, and parent-reported ADHD and ODD symptoms with self-reported and parent-reported bullying victimization, perpetration, and victimization-perpetration were examined using logistic regression analysis. The results found that the agreement between self-reported and parent-reported bullying involvement was low. Compared with bullying involvement experiences reported by adolescents themselves, parents reported higher rates of pure bullying victimization (23.7% vs. 17.8%) and victimization-perpetration (28.8% vs. 9.1%) but a lower rate of pure bullying perpetration (5.9% vs. 9.1%). Deficit in socio-communication increases the risk of being pure victims and victim-perpetrators. Parent-reported victim-perpetrators had more severe ODD symptoms than did parent-reported pure victims.


Subject(s)
Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit and Disruptive Behavior Disorders/psychology , Autism Spectrum Disorder/psychology , Bullying/psychology , Bullying/statistics & numerical data , Crime Victims/statistics & numerical data , Parents/psychology , Adolescent , Child , Crime Victims/psychology , Female , Humans , Male , Prevalence , Self Report/statistics & numerical data , Taiwan
20.
J Autism Dev Disord ; 49(10): 4170-4180, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31267285

ABSTRACT

The present study examined the associations between cyberbullying involvement and sociodemographic characteristics, autistic social impairment and attention-deficit/hyperactivity disorder and oppositional defiant disorder (ODD) symptoms in 219 adolescents with high-functioning autism spectrum disorder (ASD). Moreover, the associations between cyberbullying involvement and depression, anxiety, and suicidality were also examined. Adolescents self-reported higher rates of being a victim or perpetrator of cyberbullying than were reported by their parents. Increased age and had more severe ODD symptoms were significantly associated with being victims or perpetrators of cyberbullying. Being a victim but not a perpetrator of cyberbullying was significantly associated with depression, anxiety, and suicidality. Cyberbullying victimization and perpetration should be routinely surveyed in adolescents with high-functioning ASD.


Subject(s)
Anxiety Disorders/epidemiology , Autism Spectrum Disorder/epidemiology , Crime Victims/statistics & numerical data , Cyberbullying/statistics & numerical data , Depressive Disorder/epidemiology , Suicide/statistics & numerical data , Adolescent , Adolescent Behavior , Anxiety Disorders/psychology , Autism Spectrum Disorder/psychology , Crime Victims/psychology , Cyberbullying/psychology , Female , Humans , Male , Parents , Self Report , Suicide/psychology
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