Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. P... more Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease developme...
Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatm... more Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatment of patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of HFNC, impulse oscillation system (IOS) is a new noninvasive technique in measuring the impedance of different portions of lungs. It shows higher sensitivity in contrast to conventional pulmonary function tests (PFT). However, whether IOS is an appropriate technique to evaluate the efficacy of HFNC in improving the impedance of small airways or peripheral lung in patients with COPD is still unclear. We enrolled 26 stable COPD participants randomised into two groups receiving HFNC or nasal cannula (NC) for 10 min followed by a 4-week washout period and crossover alternatively. IOS was used to detect the difference of respiratory impedance after HFNC or NC interventions. IOS parameters, PFT results, transcutaneous partial pressure of carbon dioxide, peripheral oxygen saturation, body temperature, ...
To measure the ion activities of cells, an easy-access and fully-integrated system is necessary i... more To measure the ion activities of cells, an easy-access and fully-integrated system is necessary in culture room with high cleanness and easy maintenance. A new sensor structure integrated with readout system based on light-addressable potentiometric sensor (LAPS) to quantitatively monitor real-time cell activity with the advantages of label free and 2D image ability is proposed. The difference of cell number and acidification could be easily observed by 2D images by means of this proposed methodology.
Molecular Therapy - Methods & Clinical Development, 2020
Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This ra... more Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This rate is known as epilepsy of unknown etiology (EUE). Dysregulation of microRNAs (miRNAs) is recognized to contribute to mental disorders, including epilepsy. However, miRNA dysregulation is poorly understood in EUE. Here, we conducted miRNA expression profiling of EUE by microarray technology and identified 57 pathogenic changed miRNAs with significance. The data and bioinformatic analysis results indicated that among these miR-NAs, hsa-microRNA (miR)-1275 was highly associated with neurological disorders. Subsequently, new samples of serum and cerebrospinal fluid were collected for validation of hsa-miR-1275 expression by TaqMan assays. Results show that hsa-miR-1275 in serums of EUE were increased significantly, but in cerebrospinal fluid, the miRNA was decreased. Moreover, the MECP2 gene was selected as a hsa-miR-1275 target based on target prediction tools and gene ontology analysis. Validation of in vitro tests proved that MECP2 expression was specifically inhibited by hsa-miR-1275. Additionally, overexpression of hsa-miR-1275 can elevate expression of nuclear factor kB (NF-kB) and promote cell apoptosis. Taken together, hsa-miR-1275 might represent a novel biomarker targeting MECP2 for human EUE.
International Journal of Biological Sciences, 2020
The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remai... more The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in large human cohort. Significant compositional and functional differences in the intestinal microbiota (by 16S rRNA gene sequencing) were noted among 30 controls and 92 (31 mild, 30 moderate and 31 advanced) patients at different chronic kidney disease (CKD) stages (discovery cohort). A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at early-stage of disease. The performance was further confirmed in a validation cohort comprising 22 controls and 76 peritoneal dialysis patients. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified. Prediction of the functional capabilities of microbial communities showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages. Collectively, our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of chronic kidney disease and highlight a usefulness of specific gut microorganisms as possible disease differentiate marker of this global health burden.
To investigate the ion activities of cells based on light-addressable potentiometric sensor (LAPS... more To investigate the ion activities of cells based on light-addressable potentiometric sensor (LAPS) platform, various high-dielectric constant sensing membrane were investigated the visibility and potential issue. Three different kinds of well-proven materials in semiconductor industry, such as Si3N4, NbOx, and TiN, are the promising sensing membranes to directly culture C3A cells. TiN and NbOx could be the potential candidate. The photocurrent and flatband voltage difference generated by acidification reaction is verified to observe by LAPS is the future.
The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom increasingly used as a die... more The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom increasingly used as a dietary supplement for various health conditions, including fatigue, chronic inflammation, and male impotence. Here, we propose strategies to address the existing challenges related to the study and commercial production of this mysterious fungus.
Background: Mycobacterium abscessus complex (MABC) is the most common non-tuberculous mycobacteri... more Background: Mycobacterium abscessus complex (MABC) is the most common non-tuberculous mycobacterium that causes complicated skin and soft tissue infections (cSSTIs). The selection of antimycobacterial agents for successful treatment of such infections is a critical issue. Objectives: To investigate the antimicrobial susceptibility patterns of MABC isolates from skin and soft tissue to a variety of antimycobacterial agents. Methods: Sixty-seven MABC isolates were collected and partial gene sequencing of secA1, rpoB and hsp65 was used to classify them into three subspecies: M. abscessus subsp. abscessus (MAB), M. abscessus subsp. massiliense (MMA) and M. abscessus subsp. bolletii (MBO). The MICs of 11 antimycobacterial agents for these 67 isolates were determined using a broth microdilution method and commercial Sensititre RAPMYCOI MIC plates, as recommended by CLSI. Results: In total, 28 MAB, 38 MMA and 1 MBO were isolated from patients with cSSTIs at our hospital. Most MABC strains were resistant to ciprofloxacin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin and trimethoprim/sulfamethoxazole. In addition, most MABC strains were intermediately susceptible or resistant to cefoxitin. Eighteen of the 28 MABs and 1 MBO isolate harboured the T28 polymorphism in the erm(41) gene. Two of the 38 MMA isolates had an rrl A2059G point mutation. Most of the MABC strains were susceptible to amikacin and tigecycline. Conclusions: In Taiwan, amikacin, clarithromycin and tigecycline have good activity against MMA and MAB erm(41) C28 sequevar isolates, whereas amikacin and tigecycline, rather than clarithromycin, have good activity against both MBO and MAB erm(41) T28 sequevar isolates. Clinical trials are warranted to correlate these data with clinical outcomes.
A white organic light-emitting diode (OLED) with enhanced sensitivity has been demonstrated as a ... more A white organic light-emitting diode (OLED) with enhanced sensitivity has been demonstrated as a novel light source in a portable surface plasmon resonance (SPR) optical biosensor. A disposable broad-spectral OLED was employed on the leg side of isosceles trapezoid prism for a fixed angle of incident light. Bimetallic Au/Ag composition layers were used as sensing layers and their composition evaluated such that the wavelength resonance occurred at the peak of the light spectrum. The SPR signal detection applied differential intensities at two reference wavelengths. We show that the integration of a white-spectral OLED on an SPR sensor improved the sensor's sensitivity by ~19.29% compared to an SPR sensor system using a green OLED as a bimetallic Ag/Au sensing layer. The limit of detection (LOD) of 2.4 × 10-6 refractive index units (RIU) has been established in the range of refractive index samples (∆n) around 3.6 × 10-3 RIU. This optical sensor demonstrated the capability of real-time monitoring, self-assembled monolayer (SAM) activation, antibody immobilization, and biomolecular interaction detection of immunoglobulin G (IgG) protein with a detection limit around 40.3 pg/mL.
This work develops a highly sensitive immunoassay sensor for use in graphene oxide sheet (GOS)-ba... more This work develops a highly sensitive immunoassay sensor for use in graphene oxide sheet (GOS)-based surface plasmon resonance (SPR) chips. This sensing film, which is formed by chemically modifying a GOS surface, has covalent bonds that strongly interact with the bovine serum albumin (BSA), explaining why it has a higher sensitivity. This GOS film-based SPR chip has a BSA concentration detection limit that is 100 times higher than that of the conventional Au-film-based sensor. The affinity constants (K A) on the GOS film-based SPR chip and the conventional SPR chip for 100 μg/ml BSA are 80.82 × 10 6 M −1 and 15.67 × 10 6 M −1 , respectively. Therefore, the affinity constant of the GOS film-based SPR chip is 5.2 times higher than that of the conventional chip. With respect to the protein-protein interaction, the SPR sensor capability to detect angle changes at a low concentration anti-BSA of 75.75 nM on the GOS film-based SPR chip and the conventional SPR chip is 36.1867 and 26.1759 mdeg, respectively. At a high concentration, anti-BSA of 378.78 nM on the GOS film-based SPR chip and the conventional SPR chip reveals two times increases in the SPR angle shift. Above results demonstrate that the GOS film is promising for highly sensitive clinical diagnostic applications.
The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Tuberculosis is one of notifiable infectious diseases which may cause serious epidemic problems. ... more Tuberculosis is one of notifiable infectious diseases which may cause serious epidemic problems. Traditional diagnostic techniques include acid-fast stain, bacteria culture, metabolic monitoring have some disadvantages such as low sensitivity, time consumption and less specificity. In this study we proposed a new diagnostic technique based on the protein chips concept which detected by SPR phenomena. It was found that the resonance angle (~51.86°) shifted slightly toward right with antibody concentration of 10X, 30X, 100X, and 300X dilution under optimal concentration of immobilized TB antigen W38 (MW 41.5 kDa, 50 µg/ml). While for the W06 (MW 14 kDa, 50 µg/ml), the resonance angle was around 50.13° and shifted with the same trend as W38 did.
Objectives We aimed to determine the optimal cutoff of the immunochemical faecal occult blood tes... more Objectives We aimed to determine the optimal cutoff of the immunochemical faecal occult blood test (iFOBT) by using cost-effectiveness analysis. Methods A total of 22,672 subjects aged 50 years or older were invited to have an uptake of iFOBT. We collected data from screen-detected cases for the cutoff above 100 ng/mL and obtained interval cancers from a nationwide cancer registry for a cutoff below 100 ng/mL. We found a total of 65 colorectal cancer (CRC) cases, including 43 detected by screen and 22 diagnosed between screens (interval cases). The optimal cutoff was first determined by receiver operating characteristics (ROC) curve analysis. Formal economic evaluation was further applied to identifying the optimal cutoff by assessing the minimum incremental cost-effectiveness ratio (ICER), an indicator for cost per life year gained (effectiveness), given a series of cutoffs of iFOBT, ranging from 30 to 200 ng/mL compared with no screening. Results ROC curve analysis found the optimal cutoff of iFOBT to be 100 ng/mL at which the sensitivity, false-positive and odds of being affected given a positive result were 81.5% (70.2%-89.2%), 5.7% (5.4%-6.0%) and 1.24 (1.19-1.32), respectively. The area under ROC curve was 0.87 (0.81-0.93). In economic appraisal, the screening programme irrespective of any cutoff dominated (less cost and more effectiveness) over the control group. The optimal cutoff (the lowest ICER) was 110 ng/mL at which an average of 0.054 life year was gained and that of 950 ($US) was saved. Conclusions We used cost-effectiveness to identify 110 ng/mL as the optimal cutoff of iFOBT in a Taiwanese population-based screening for CRC. Our model provides a useful approach for health policy-makers in designing population-based screening for CRC to determine the optimal cutoff of iFOBT when cost and effectiveness need to be taken into account.
Mycobacterium abscessus is a non-tuberculous mycobacterium. It can cause diseases in both immunos... more Mycobacterium abscessus is a non-tuberculous mycobacterium. It can cause diseases in both immunosuppressed and immunocompetent patients and is highly resistant to multiple antimicrobial agents. M. abscessus displays two different colony morphology types: smooth and rough morphotypes. Cells with a rough morphotype are more virulent. The purpose of this study was to identify genes responsible for M. abscessus morphotype switching. With transposon mutagenesis, a mutant with a Tn5 inserted into the promoter region of the mab_3168c gene was found to switch its colonies from a rough to a smooth morphotype. This mutant had a higher sliding motility but a lower ability to form biofilms, aggregate in culture, and survive inside macrophages. Results of bioinformatic analyses suggest that the putative Mab_3168c protein is a member of the GCN5-related N-acetyltransferase superfamily. This prediction was supported by the demonstration that the mab_3168c gene conferred M. abscessus and M. smegmatis cells resistance to amikacin. The multiple roles of mab_3168c suggest that it could be a potential target for development of therapeutic regimens to treat diseases caused by M. abscessus.
An organic light emitting diode (OLED) was integrated with a brightness enhancement film (BEF) an... more An organic light emitting diode (OLED) was integrated with a brightness enhancement film (BEF) and giant birefringent optical (GBO) film as a light source for a surface plasmon resonance (SPR) sensor system, to attain a portable SPR sensor design with further light source miniaturization that is simple to construct and costeffective. It was found that by using OLED-BEF-GBO film based SPR, the quality of the signal is improved. A method for calculating SPR signal by summing the differences in optical intensity at two different wavelengths was employed to minimize the effect of the noise error particularly in portable SPR devices. The experimental results confirmed that the limit of detection (LOD) of the SPR using an Au sensing layer has an effective refractive index change of 7.8 × 10-6 refractive index units (RIU). Furthermore, for the SPR system using Au/Ag sensing metal layers, an LOD of 3.2 × 10-6 RIU was achieved due to a better sensitivity and resolution value. While for bio-affinity goat anti-mouse Immunoglobulin G (IgG) and target sample mouse IgG protein, the LOD is around 40.6 pg/ml.
The fluorescein labelled antibody/Fluorescence Activated Cell Sorter (Ab/FACS) assay was used for... more The fluorescein labelled antibody/Fluorescence Activated Cell Sorter (Ab/FACS) assay was used for direct identification of Legionella pneumophila from the cooling tower samples around the Taipei city area, Taiwan during the period of 8/1998 to7/1999. For comparison, conventional Legionella culture method was also performed in parallel. Specimen harvested directly from the cooling towers were first concentrated by filtration through a millipore membrane, bacteria contained in the suspension were then inoculated on BCYE-α (L-cysteine)/BAP plates for isolation and also direct identification by Ab/FACS assay. Latex agglutination and Ab/FACS with antibody specific to L. pneumophila serogroup 1 were subsequently performed for differentiation of the L. pneumophila serogroup-1 strains from other sero-groups. Of the 403 specimens, a total of 205 colonies suspected to be L. pneumophila were isolated. A total of 177 colonies were confirmed to be L. pneumophila by biochemical analysis. After latex agglutination, 105 strains were classified to be L. pneumophila serogroup 1, and 72 strains to be L. pneumophila non-serogroup 1. In parallel, the Ab/FACS assay showed good concordance with the traditional identification and typing method. Our study suggests that Ab/FACS appears to be a rapid and efficient technique for identification of L. pneumophila from the environment.
The full-length sequences of the groESL genes (also known as cpn10/60 ) of Streptococcus anginosu... more The full-length sequences of the groESL genes (also known as cpn10/60 ) of Streptococcus anginosus , Streptococcus constellatus , Streptococcus gordonii , and Streptococcus sanguis and the near full-length sequence of the groESL genes of Streptococcus intermedius , Streptococcus bovis , Streptococcus mitis , Streptococcus mutans , Streptococcus oralis , and Streptococcus salivarius were determined. The lengths of the groES genes from the 10 species listed above ranged from 282 to 288 bp, and the full-length sequences of groEL determined for 4 species ( S. anginosus , S. constellatus , S. gordonii , and S. sanguis ) revealed that each was 1,623 bp. The intergenic region (spacer) between the groES and groEL genes varies in size (15 to 111 bp) and sequence between species. The variation of the groES sequences among the species tested was greater (62.1 to 95.1% nucleotide sequence identities) than that of the groEL sequences (77.2 to 95.2% nucleotide sequence identities). Phylogenetic a...
The performance of a nested PCR-based assay (the RAPID BAP-MTB; AsiaGen, Taichung, Taiwan) and th... more The performance of a nested PCR-based assay (the RAPID BAP-MTB; AsiaGen, Taichung, Taiwan) and the BD ProbeTec ET (DTB) system (Becton Dickinson, Sparks, Md.) for detection of Mycobacterium tuberculosis was evaluated with 600 consecutive clinical samples. These samples, including 552 respiratory specimens and 48 nonrespiratory specimens, were collected from 333 patients treated at National Taiwan University Hospital from September to October 2003. The results of both assays were compared to the gold standard of combined culture results and clinical diagnosis. The overall sensitivity and specificity of the RAPID BAP-MTB assay for respiratory specimens were 66.7% and 97.2%, respectively, and for the DTB assay they were 56.7% and 95.3%, respectively. The positive and negative predictive values for the RAPID BAP-MTB were 74.1% and 96.0%, respectively, and for the DTB assay they were 59.6% and 94.7%, respectively. For smear-negative samples, the sensitivity of the RAPID BAP-MTB and DTB a...
Objectives: Mycobacterium kansasii causes a variety of infections. Although previous reports on t... more Objectives: Mycobacterium kansasii causes a variety of infections. Although previous reports on the prognosis of antimicrobial therapy have been mostly satisfactory, problems involving treatment failure or relapse have been encountered. The purpose of this study was to establish a relationship between the clinical treatment outcomes of M. kansasii infections and bacterial drug susceptibility, and their clonality. Methods: A total of 37 M. kansasii clinical isolates and clinical information on 34 patients were retrospectively collected in a tertiary medical centre in Taiwan. Bacterial drug susceptibility was determined by the microdilution method. The phylogenetic relationship was analysed by PFGE analysis. Results: Results of PFGE typing revealed a major cluster (cluster I) and eight other divergent patterns. Two/three strains leading to treatment failure were also multidrug resistant and belonged to cluster I. Conclusions: A relationship between high drug resistance and genetic relatedness of some M. kansasii strains was established. This was associated with clinical treatment failure.
American Journal of Respiratory and Critical Care Medicine, 2009
Rationale: Fluoroquinolones are the most commonly prescribed antibiotic class in the United State... more Rationale: Fluoroquinolones are the most commonly prescribed antibiotic class in the United States. They have the potential to become first-line antituberculosis therapy, but the effect of fluoroquinolone use on fluoroquinolone resistance in Mycobacterium tuberculosis is not well characterized. Objectives: To determine the prevalence of and risk factors for fluoroquinolone-resistant tuberculosis in a large United States population. Methods: We identified all people with culture-confirmed tuberculosis enrolled in TennCare (Medicaid) and reported to the Tennessee Department of Health from January 2002 to December 2006. People with fluoroquinolone-resistant M. tuberculosis isolates (cases) were compared with those with susceptible isolates (control subjects). Fluoroquinolone resistance was determined by agar proportion using ofloxacin 2 mg/ml. Outpatient fluoroquinolone exposure in the 12 months before tuberculosis diagnosis was ascertained from TennCare pharmacy data. Measurements and Main Results: Of 640 study patients, 116 (18%) had fluoroquinolone exposure in the 12 months before diagnosis, and 16 (2.5%; 95% confidence interval [CI], 1.4-4.0%) M. tuberculosis isolates were fluoroquinolone resistant. Among the 54 patients with more than 10 days of fluoroquinolone exposure, 7 (13%) had fluoroquinolone resistance. In multivariable logistic regression analyses using propensity score to control for age, sex, race, HIV serostatus, and site of disease, more than 10 days of fluoroquinolone exposure before tuberculosis diagnosis was associated with fluoroquinolone resistance (odds ratio 7.0; 95% CI, 2.3-20.6; P 5 0.001). Fluoroquinolone exposure for more than 10 days that occurred more than 60 days before tuberculosis diagnosis was associated with the highest risk of resistance (20.8%; odds ratio 17.0; 95% CI, 5.1-56.8; P , 0.001 compared with no exposure). Conclusions: Overall, fluoroquinolone resistance was relatively low. However, receipt of fluoroquinolones for more than 10 days, particularly more than 60 days before tuberculosis diagnosis, was associated with a high risk of fluoroquinolone-resistant tuberculosis.
The image in Fig. 1e of this Article showing the 'HFD þ 8%' group was inadvertently duplicated fr... more The image in Fig. 1e of this Article showing the 'HFD þ 8%' group was inadvertently duplicated from the 'Chow þ 8%' group. The correct version of the figure appears below.
Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. P... more Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease developme...
Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatm... more Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatment of patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of HFNC, impulse oscillation system (IOS) is a new noninvasive technique in measuring the impedance of different portions of lungs. It shows higher sensitivity in contrast to conventional pulmonary function tests (PFT). However, whether IOS is an appropriate technique to evaluate the efficacy of HFNC in improving the impedance of small airways or peripheral lung in patients with COPD is still unclear. We enrolled 26 stable COPD participants randomised into two groups receiving HFNC or nasal cannula (NC) for 10 min followed by a 4-week washout period and crossover alternatively. IOS was used to detect the difference of respiratory impedance after HFNC or NC interventions. IOS parameters, PFT results, transcutaneous partial pressure of carbon dioxide, peripheral oxygen saturation, body temperature, ...
To measure the ion activities of cells, an easy-access and fully-integrated system is necessary i... more To measure the ion activities of cells, an easy-access and fully-integrated system is necessary in culture room with high cleanness and easy maintenance. A new sensor structure integrated with readout system based on light-addressable potentiometric sensor (LAPS) to quantitatively monitor real-time cell activity with the advantages of label free and 2D image ability is proposed. The difference of cell number and acidification could be easily observed by 2D images by means of this proposed methodology.
Molecular Therapy - Methods & Clinical Development, 2020
Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This ra... more Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This rate is known as epilepsy of unknown etiology (EUE). Dysregulation of microRNAs (miRNAs) is recognized to contribute to mental disorders, including epilepsy. However, miRNA dysregulation is poorly understood in EUE. Here, we conducted miRNA expression profiling of EUE by microarray technology and identified 57 pathogenic changed miRNAs with significance. The data and bioinformatic analysis results indicated that among these miR-NAs, hsa-microRNA (miR)-1275 was highly associated with neurological disorders. Subsequently, new samples of serum and cerebrospinal fluid were collected for validation of hsa-miR-1275 expression by TaqMan assays. Results show that hsa-miR-1275 in serums of EUE were increased significantly, but in cerebrospinal fluid, the miRNA was decreased. Moreover, the MECP2 gene was selected as a hsa-miR-1275 target based on target prediction tools and gene ontology analysis. Validation of in vitro tests proved that MECP2 expression was specifically inhibited by hsa-miR-1275. Additionally, overexpression of hsa-miR-1275 can elevate expression of nuclear factor kB (NF-kB) and promote cell apoptosis. Taken together, hsa-miR-1275 might represent a novel biomarker targeting MECP2 for human EUE.
International Journal of Biological Sciences, 2020
The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remai... more The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in large human cohort. Significant compositional and functional differences in the intestinal microbiota (by 16S rRNA gene sequencing) were noted among 30 controls and 92 (31 mild, 30 moderate and 31 advanced) patients at different chronic kidney disease (CKD) stages (discovery cohort). A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at early-stage of disease. The performance was further confirmed in a validation cohort comprising 22 controls and 76 peritoneal dialysis patients. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified. Prediction of the functional capabilities of microbial communities showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages. Collectively, our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of chronic kidney disease and highlight a usefulness of specific gut microorganisms as possible disease differentiate marker of this global health burden.
To investigate the ion activities of cells based on light-addressable potentiometric sensor (LAPS... more To investigate the ion activities of cells based on light-addressable potentiometric sensor (LAPS) platform, various high-dielectric constant sensing membrane were investigated the visibility and potential issue. Three different kinds of well-proven materials in semiconductor industry, such as Si3N4, NbOx, and TiN, are the promising sensing membranes to directly culture C3A cells. TiN and NbOx could be the potential candidate. The photocurrent and flatband voltage difference generated by acidification reaction is verified to observe by LAPS is the future.
The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom increasingly used as a die... more The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom increasingly used as a dietary supplement for various health conditions, including fatigue, chronic inflammation, and male impotence. Here, we propose strategies to address the existing challenges related to the study and commercial production of this mysterious fungus.
Background: Mycobacterium abscessus complex (MABC) is the most common non-tuberculous mycobacteri... more Background: Mycobacterium abscessus complex (MABC) is the most common non-tuberculous mycobacterium that causes complicated skin and soft tissue infections (cSSTIs). The selection of antimycobacterial agents for successful treatment of such infections is a critical issue. Objectives: To investigate the antimicrobial susceptibility patterns of MABC isolates from skin and soft tissue to a variety of antimycobacterial agents. Methods: Sixty-seven MABC isolates were collected and partial gene sequencing of secA1, rpoB and hsp65 was used to classify them into three subspecies: M. abscessus subsp. abscessus (MAB), M. abscessus subsp. massiliense (MMA) and M. abscessus subsp. bolletii (MBO). The MICs of 11 antimycobacterial agents for these 67 isolates were determined using a broth microdilution method and commercial Sensititre RAPMYCOI MIC plates, as recommended by CLSI. Results: In total, 28 MAB, 38 MMA and 1 MBO were isolated from patients with cSSTIs at our hospital. Most MABC strains were resistant to ciprofloxacin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin and trimethoprim/sulfamethoxazole. In addition, most MABC strains were intermediately susceptible or resistant to cefoxitin. Eighteen of the 28 MABs and 1 MBO isolate harboured the T28 polymorphism in the erm(41) gene. Two of the 38 MMA isolates had an rrl A2059G point mutation. Most of the MABC strains were susceptible to amikacin and tigecycline. Conclusions: In Taiwan, amikacin, clarithromycin and tigecycline have good activity against MMA and MAB erm(41) C28 sequevar isolates, whereas amikacin and tigecycline, rather than clarithromycin, have good activity against both MBO and MAB erm(41) T28 sequevar isolates. Clinical trials are warranted to correlate these data with clinical outcomes.
A white organic light-emitting diode (OLED) with enhanced sensitivity has been demonstrated as a ... more A white organic light-emitting diode (OLED) with enhanced sensitivity has been demonstrated as a novel light source in a portable surface plasmon resonance (SPR) optical biosensor. A disposable broad-spectral OLED was employed on the leg side of isosceles trapezoid prism for a fixed angle of incident light. Bimetallic Au/Ag composition layers were used as sensing layers and their composition evaluated such that the wavelength resonance occurred at the peak of the light spectrum. The SPR signal detection applied differential intensities at two reference wavelengths. We show that the integration of a white-spectral OLED on an SPR sensor improved the sensor's sensitivity by ~19.29% compared to an SPR sensor system using a green OLED as a bimetallic Ag/Au sensing layer. The limit of detection (LOD) of 2.4 × 10-6 refractive index units (RIU) has been established in the range of refractive index samples (∆n) around 3.6 × 10-3 RIU. This optical sensor demonstrated the capability of real-time monitoring, self-assembled monolayer (SAM) activation, antibody immobilization, and biomolecular interaction detection of immunoglobulin G (IgG) protein with a detection limit around 40.3 pg/mL.
This work develops a highly sensitive immunoassay sensor for use in graphene oxide sheet (GOS)-ba... more This work develops a highly sensitive immunoassay sensor for use in graphene oxide sheet (GOS)-based surface plasmon resonance (SPR) chips. This sensing film, which is formed by chemically modifying a GOS surface, has covalent bonds that strongly interact with the bovine serum albumin (BSA), explaining why it has a higher sensitivity. This GOS film-based SPR chip has a BSA concentration detection limit that is 100 times higher than that of the conventional Au-film-based sensor. The affinity constants (K A) on the GOS film-based SPR chip and the conventional SPR chip for 100 μg/ml BSA are 80.82 × 10 6 M −1 and 15.67 × 10 6 M −1 , respectively. Therefore, the affinity constant of the GOS film-based SPR chip is 5.2 times higher than that of the conventional chip. With respect to the protein-protein interaction, the SPR sensor capability to detect angle changes at a low concentration anti-BSA of 75.75 nM on the GOS film-based SPR chip and the conventional SPR chip is 36.1867 and 26.1759 mdeg, respectively. At a high concentration, anti-BSA of 378.78 nM on the GOS film-based SPR chip and the conventional SPR chip reveals two times increases in the SPR angle shift. Above results demonstrate that the GOS film is promising for highly sensitive clinical diagnostic applications.
The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Tuberculosis is one of notifiable infectious diseases which may cause serious epidemic problems. ... more Tuberculosis is one of notifiable infectious diseases which may cause serious epidemic problems. Traditional diagnostic techniques include acid-fast stain, bacteria culture, metabolic monitoring have some disadvantages such as low sensitivity, time consumption and less specificity. In this study we proposed a new diagnostic technique based on the protein chips concept which detected by SPR phenomena. It was found that the resonance angle (~51.86°) shifted slightly toward right with antibody concentration of 10X, 30X, 100X, and 300X dilution under optimal concentration of immobilized TB antigen W38 (MW 41.5 kDa, 50 µg/ml). While for the W06 (MW 14 kDa, 50 µg/ml), the resonance angle was around 50.13° and shifted with the same trend as W38 did.
Objectives We aimed to determine the optimal cutoff of the immunochemical faecal occult blood tes... more Objectives We aimed to determine the optimal cutoff of the immunochemical faecal occult blood test (iFOBT) by using cost-effectiveness analysis. Methods A total of 22,672 subjects aged 50 years or older were invited to have an uptake of iFOBT. We collected data from screen-detected cases for the cutoff above 100 ng/mL and obtained interval cancers from a nationwide cancer registry for a cutoff below 100 ng/mL. We found a total of 65 colorectal cancer (CRC) cases, including 43 detected by screen and 22 diagnosed between screens (interval cases). The optimal cutoff was first determined by receiver operating characteristics (ROC) curve analysis. Formal economic evaluation was further applied to identifying the optimal cutoff by assessing the minimum incremental cost-effectiveness ratio (ICER), an indicator for cost per life year gained (effectiveness), given a series of cutoffs of iFOBT, ranging from 30 to 200 ng/mL compared with no screening. Results ROC curve analysis found the optimal cutoff of iFOBT to be 100 ng/mL at which the sensitivity, false-positive and odds of being affected given a positive result were 81.5% (70.2%-89.2%), 5.7% (5.4%-6.0%) and 1.24 (1.19-1.32), respectively. The area under ROC curve was 0.87 (0.81-0.93). In economic appraisal, the screening programme irrespective of any cutoff dominated (less cost and more effectiveness) over the control group. The optimal cutoff (the lowest ICER) was 110 ng/mL at which an average of 0.054 life year was gained and that of 950 ($US) was saved. Conclusions We used cost-effectiveness to identify 110 ng/mL as the optimal cutoff of iFOBT in a Taiwanese population-based screening for CRC. Our model provides a useful approach for health policy-makers in designing population-based screening for CRC to determine the optimal cutoff of iFOBT when cost and effectiveness need to be taken into account.
Mycobacterium abscessus is a non-tuberculous mycobacterium. It can cause diseases in both immunos... more Mycobacterium abscessus is a non-tuberculous mycobacterium. It can cause diseases in both immunosuppressed and immunocompetent patients and is highly resistant to multiple antimicrobial agents. M. abscessus displays two different colony morphology types: smooth and rough morphotypes. Cells with a rough morphotype are more virulent. The purpose of this study was to identify genes responsible for M. abscessus morphotype switching. With transposon mutagenesis, a mutant with a Tn5 inserted into the promoter region of the mab_3168c gene was found to switch its colonies from a rough to a smooth morphotype. This mutant had a higher sliding motility but a lower ability to form biofilms, aggregate in culture, and survive inside macrophages. Results of bioinformatic analyses suggest that the putative Mab_3168c protein is a member of the GCN5-related N-acetyltransferase superfamily. This prediction was supported by the demonstration that the mab_3168c gene conferred M. abscessus and M. smegmatis cells resistance to amikacin. The multiple roles of mab_3168c suggest that it could be a potential target for development of therapeutic regimens to treat diseases caused by M. abscessus.
An organic light emitting diode (OLED) was integrated with a brightness enhancement film (BEF) an... more An organic light emitting diode (OLED) was integrated with a brightness enhancement film (BEF) and giant birefringent optical (GBO) film as a light source for a surface plasmon resonance (SPR) sensor system, to attain a portable SPR sensor design with further light source miniaturization that is simple to construct and costeffective. It was found that by using OLED-BEF-GBO film based SPR, the quality of the signal is improved. A method for calculating SPR signal by summing the differences in optical intensity at two different wavelengths was employed to minimize the effect of the noise error particularly in portable SPR devices. The experimental results confirmed that the limit of detection (LOD) of the SPR using an Au sensing layer has an effective refractive index change of 7.8 × 10-6 refractive index units (RIU). Furthermore, for the SPR system using Au/Ag sensing metal layers, an LOD of 3.2 × 10-6 RIU was achieved due to a better sensitivity and resolution value. While for bio-affinity goat anti-mouse Immunoglobulin G (IgG) and target sample mouse IgG protein, the LOD is around 40.6 pg/ml.
The fluorescein labelled antibody/Fluorescence Activated Cell Sorter (Ab/FACS) assay was used for... more The fluorescein labelled antibody/Fluorescence Activated Cell Sorter (Ab/FACS) assay was used for direct identification of Legionella pneumophila from the cooling tower samples around the Taipei city area, Taiwan during the period of 8/1998 to7/1999. For comparison, conventional Legionella culture method was also performed in parallel. Specimen harvested directly from the cooling towers were first concentrated by filtration through a millipore membrane, bacteria contained in the suspension were then inoculated on BCYE-α (L-cysteine)/BAP plates for isolation and also direct identification by Ab/FACS assay. Latex agglutination and Ab/FACS with antibody specific to L. pneumophila serogroup 1 were subsequently performed for differentiation of the L. pneumophila serogroup-1 strains from other sero-groups. Of the 403 specimens, a total of 205 colonies suspected to be L. pneumophila were isolated. A total of 177 colonies were confirmed to be L. pneumophila by biochemical analysis. After latex agglutination, 105 strains were classified to be L. pneumophila serogroup 1, and 72 strains to be L. pneumophila non-serogroup 1. In parallel, the Ab/FACS assay showed good concordance with the traditional identification and typing method. Our study suggests that Ab/FACS appears to be a rapid and efficient technique for identification of L. pneumophila from the environment.
The full-length sequences of the groESL genes (also known as cpn10/60 ) of Streptococcus anginosu... more The full-length sequences of the groESL genes (also known as cpn10/60 ) of Streptococcus anginosus , Streptococcus constellatus , Streptococcus gordonii , and Streptococcus sanguis and the near full-length sequence of the groESL genes of Streptococcus intermedius , Streptococcus bovis , Streptococcus mitis , Streptococcus mutans , Streptococcus oralis , and Streptococcus salivarius were determined. The lengths of the groES genes from the 10 species listed above ranged from 282 to 288 bp, and the full-length sequences of groEL determined for 4 species ( S. anginosus , S. constellatus , S. gordonii , and S. sanguis ) revealed that each was 1,623 bp. The intergenic region (spacer) between the groES and groEL genes varies in size (15 to 111 bp) and sequence between species. The variation of the groES sequences among the species tested was greater (62.1 to 95.1% nucleotide sequence identities) than that of the groEL sequences (77.2 to 95.2% nucleotide sequence identities). Phylogenetic a...
The performance of a nested PCR-based assay (the RAPID BAP-MTB; AsiaGen, Taichung, Taiwan) and th... more The performance of a nested PCR-based assay (the RAPID BAP-MTB; AsiaGen, Taichung, Taiwan) and the BD ProbeTec ET (DTB) system (Becton Dickinson, Sparks, Md.) for detection of Mycobacterium tuberculosis was evaluated with 600 consecutive clinical samples. These samples, including 552 respiratory specimens and 48 nonrespiratory specimens, were collected from 333 patients treated at National Taiwan University Hospital from September to October 2003. The results of both assays were compared to the gold standard of combined culture results and clinical diagnosis. The overall sensitivity and specificity of the RAPID BAP-MTB assay for respiratory specimens were 66.7% and 97.2%, respectively, and for the DTB assay they were 56.7% and 95.3%, respectively. The positive and negative predictive values for the RAPID BAP-MTB were 74.1% and 96.0%, respectively, and for the DTB assay they were 59.6% and 94.7%, respectively. For smear-negative samples, the sensitivity of the RAPID BAP-MTB and DTB a...
Objectives: Mycobacterium kansasii causes a variety of infections. Although previous reports on t... more Objectives: Mycobacterium kansasii causes a variety of infections. Although previous reports on the prognosis of antimicrobial therapy have been mostly satisfactory, problems involving treatment failure or relapse have been encountered. The purpose of this study was to establish a relationship between the clinical treatment outcomes of M. kansasii infections and bacterial drug susceptibility, and their clonality. Methods: A total of 37 M. kansasii clinical isolates and clinical information on 34 patients were retrospectively collected in a tertiary medical centre in Taiwan. Bacterial drug susceptibility was determined by the microdilution method. The phylogenetic relationship was analysed by PFGE analysis. Results: Results of PFGE typing revealed a major cluster (cluster I) and eight other divergent patterns. Two/three strains leading to treatment failure were also multidrug resistant and belonged to cluster I. Conclusions: A relationship between high drug resistance and genetic relatedness of some M. kansasii strains was established. This was associated with clinical treatment failure.
American Journal of Respiratory and Critical Care Medicine, 2009
Rationale: Fluoroquinolones are the most commonly prescribed antibiotic class in the United State... more Rationale: Fluoroquinolones are the most commonly prescribed antibiotic class in the United States. They have the potential to become first-line antituberculosis therapy, but the effect of fluoroquinolone use on fluoroquinolone resistance in Mycobacterium tuberculosis is not well characterized. Objectives: To determine the prevalence of and risk factors for fluoroquinolone-resistant tuberculosis in a large United States population. Methods: We identified all people with culture-confirmed tuberculosis enrolled in TennCare (Medicaid) and reported to the Tennessee Department of Health from January 2002 to December 2006. People with fluoroquinolone-resistant M. tuberculosis isolates (cases) were compared with those with susceptible isolates (control subjects). Fluoroquinolone resistance was determined by agar proportion using ofloxacin 2 mg/ml. Outpatient fluoroquinolone exposure in the 12 months before tuberculosis diagnosis was ascertained from TennCare pharmacy data. Measurements and Main Results: Of 640 study patients, 116 (18%) had fluoroquinolone exposure in the 12 months before diagnosis, and 16 (2.5%; 95% confidence interval [CI], 1.4-4.0%) M. tuberculosis isolates were fluoroquinolone resistant. Among the 54 patients with more than 10 days of fluoroquinolone exposure, 7 (13%) had fluoroquinolone resistance. In multivariable logistic regression analyses using propensity score to control for age, sex, race, HIV serostatus, and site of disease, more than 10 days of fluoroquinolone exposure before tuberculosis diagnosis was associated with fluoroquinolone resistance (odds ratio 7.0; 95% CI, 2.3-20.6; P 5 0.001). Fluoroquinolone exposure for more than 10 days that occurred more than 60 days before tuberculosis diagnosis was associated with the highest risk of resistance (20.8%; odds ratio 17.0; 95% CI, 5.1-56.8; P , 0.001 compared with no exposure). Conclusions: Overall, fluoroquinolone resistance was relatively low. However, receipt of fluoroquinolones for more than 10 days, particularly more than 60 days before tuberculosis diagnosis, was associated with a high risk of fluoroquinolone-resistant tuberculosis.
The image in Fig. 1e of this Article showing the 'HFD þ 8%' group was inadvertently duplicated fr... more The image in Fig. 1e of this Article showing the 'HFD þ 8%' group was inadvertently duplicated from the 'Chow þ 8%' group. The correct version of the figure appears below.
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Papers by Hsin-Chih Lai