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Synthesis of robust electrochemical substrate and fabrication of immobilization free biosensors for rapid sensing of salicylate and β-hydroxybutyrate in whole blood

Chen TY, Mani V, Huang ST, Chang PC, Huang CH, Huang NM

Anal Chim Acta, 2017 Oct 16;990:78-83.
PMID: 29029745 DOI: 10.1016/j.aca.2017.08.051

An electrochemical latent redox probe, SAF 5 was designed, synthesized and characterized. A rapid and sensitive solution-based assay was demonstrated for salicylate hydroxylase (SHL). In presence of NADH at aerobic conditions, SHL catalyzed the decarboxylative hydroxylation of SAF and released a redox reporter amino ferrocene (AF 6). The release of AF 6 was monitored at interference free potential region (-50 mV vs. Ag|AgCl) using differential pulse voltammetry as signal read-out. The current signal generated by this process is highly specific, and insensitive to other biological interfering compounds. Next, the SAF incorporated SHL assay was extended to fabricate immobilization-free biosensors for rapid sensing of salicylic acid (SA) and β-hydroxybutyrate (β-HB) in whole blood. The described method rapidly detects SA in a linear range of 35-560 μM with detection limit of 5.0 μM. For β-HB determination, the linear range was 10-600 μM and detection limit was 2.0 μM. Besides, the assay protocols are simple, fast, reliable, selective, sensitive and advantageous over existing methods. The whole blood assay did not required cumbersome steps such as, enzyme immobilization, pre-treatments and holds great practical potential in clinical diagnosis.
MiR-26b-3p Promotes Intestinal Motility Disorder by Targeting FZD10 to Inhibit GSK3β/β-Catenin Signaling and Induce Enteric Glial Cell Apoptosis

Zhan Y, Wen Y, Zheng F, Du LJ, Chen TY, Shen XL, et al.

Mol Neurobiol, 2024 Mar;61(3):1543-1561.
PMID: 37728849 DOI: 10.1007/s12035-023-03600-8

Enteric glial cells (EGCs) are the major component of the enteric nervous system and affect the pathophysiological process of intestinal motility dysfunction. MicroRNAs (miRNAs) play an important role in regulating gastrointestinal homeostasis. However, the mechanism of miRNA-mediated regulation of EGCs in intestinal dysmotility remains unclear. In this study, we investigated the effect of EGC apoptosis on intestinal dysmotility, and the effect of miR-26b-3p on EGC proliferation and apoptosis in vivo and in vitro. A loperamide hydrochloride (Lop)-induced constipated mouse model and an in vitro culture system of rat EGCs were established. The transcriptome was used to predict the differentially expressed gene miR-26b-3p and the target gene Frizzled 10 (FZD10), and their targeting binding relationship was verified by luciferase. EGCs were transfected with miR-26b-3p mimic or antagomir, and the FZD10 expression was down-regulated by siRNA. Immunofluorescence and flow cytometry were used to detect EGC apoptosis. MiR-26b-3p and FZD10 expressions were examined using quantitative real-time PCR (qRT-PCR). The CCK-8 assay was used to detect EGC proliferation. The protein levels were detected by Western blotting and enzyme-linked immunosorbent assay (ELISA). The results showed that miR-26b-3p was up-regulated in the Lop group, whereas FZD10 was down-regulated, and EGC apoptosis was increased in the colon of intestinal dysmotility mice. FZD10 down-regulation and miR-26b-3p mimic significantly increased glycogen synthase kinase-3β phosphorylation (p-GSK3β) levels, decreased β-catenin expression, and promoted EGC apoptosis. MiR-26b-3p antagomir alleviated intestinal dysmotility, promoted EGC increased activity of EGCs, and reduced EGC apoptosis in vivo. In conclusion, this study indicated that miR-26b-3p promotes intestinal motility disorders by targeting FZD10 to block GSK3β/β-catenin signaling and induces apoptosis in EGCs. Our results provide a new research target for the treatment and intervention of intestinal dysmotility.
Fulltext Audit of hypertension in general practice

Chan SC, Chandramani T, Chen TY, Chong KN, Harbaksh S, Lee TW, et al.

Med J Malaysia, 2005 Oct;60(4):475-82.
PMID: 16570710

An audit of hypertension management was done in October 2004 in nine general practice (GP) clinics. Two structure, ten process and two outcome indicators were assessed. Results showed that targets were achieved in only four indicators, i.e., weight recording (89%), BP monitoring (85.8%), follow-up interval not exceeding 6 months (87.9%) and mean diastolic BP (73.9%). The other indicators (hypertension registry, reminder mechanisms for defaulters, recording of smoking, height, fundoscopy, monitoring of lipid profile, blood sugar, ECG, renal function and achievement of target mean systolic pressure) showed adequacy percentages varying from 22.1 to 68.7. Out of the 1260 patients assessed, 743 (59%) achieved a mean BP < or = 140/90 (or < or = 130/80 mmHg with diabetes mellitus / renal insufficiency) in the last 3 recorded readings. There was a vast difference between individual clinics. Reasons for not achieving targets were discussed and remedial measures for implementation were recommended.
Factors Related to, and Effective Interventions for, Vaccination Uptake Among Older Adults in Two Asia-Pacific Countries: A Rapid Review

Tong WT, Seth A, Ng MPE, Tong SC, Lau A, Chen TY, et al.

Asia Pac J Public Health, 2024 Nov;36(8):676-688.
PMID: 38869052 DOI: 10.1177/10105395241258530

This rapid review aimed to present a comprehensive overview of barriers, facilitators, and effective interventions that promote vaccination uptake by older adults in the Asia-Pacific region. Rapid review methodology was applied, using two databases (PubMed, Embase). Articles were included if studies were conducted in Australia, Singapore, Indonesia, and the Philippines; included human population ≥50 years of age, and was published from 2016 to August 2022. Related articles were not found from Indonesia and Philippines. A total of 23 articles met the inclusion criteria, with 19 reporting on barriers and facilitators, whereas, four articles reported effective interventions to promote vaccination uptake. Among the 19 studies that identified barriers and facilitators to vaccination uptake, the more common factors were social influences (n = 8/19), perceived benefits of vaccine (n = 7/19), and perceived vaccine safety (n = 6/19). Interventions that focused on supporting clinicians were found to be effective in leading them to recommend vaccinations among older adults, such as creating awareness on the low baseline vaccination rates among older adults, provision of structured health assessment, and nurse reminders. More studies are needed to ascertain the barriers and facilitators to uptake, as well as to identify effective interventions influencing vaccine uptake among older adults in the Asia-Pacific region.
Efficacy of rabbit antithymocyte globulin as first-line treatment of severe aplastic anemia: an Asian multicenter retrospective study

Chuncharunee S, Wong R, Rojnuckarin P, Chang CS, Chang KM, Lu MY, et al.

Int J Hematol, 2016 Oct;104(4):454-61.
PMID: 27376944 DOI: 10.1007/s12185-016-2053-8

Due to the unavailability of horse antithymocyte globulin (ATG) in many markets worldwide, patients with severe aplastic anemia (SAA) are limited to the use of rabbit ATG. We aimed to analyze hematologic response and overall survival (OS) of Asian patients treated with rabbit ATG as first-line therapy of SAA. We retrospectively reviewed the medical records of 97 consecutive patients who received rabbit ATG as first-line treatment of SAA from 2006 to 2012 at centers in four Asian countries. The primary endpoint was 6- and 12-month overall response rates (ORR) for patients receiving rabbit ATG within the recommended dose range (2.5-3.75 mg/kg/day). Secondary endpoints included ORR in patients receiving any dose of rabbit ATG and 2-year OS. For patients who received rabbit ATG within the recommended dose range, 6- and 12-month ORRs were 17.4 and 63.6 %, respectively. For patients who received any dose of rabbit ATG, 6- and 12-month ORRs were 24.3 and 68.6 %, respectively. The 2-year OS rate was 86.3 %. Rabbit ATG is effective for treatment of SAA in Asian patients. The 12-month ORR and 2-year OS with rabbit ATG were comparable to historical results obtained with horse ATG.
A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis

Kim SJ, Yoon DH, Jaccard A, Chng WJ, Lim ST, Hong H, et al.

Lancet Oncol, 2016 Mar;17(3):389-400.
PMID: 26873565 DOI: 10.1016/S1470-2045(15)00533-1

BACKGROUND: The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted.
METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia

Yoon SE, Song Y, Kim SJ, Yoon DH, Chen TY, Koh Y, et al.

Lancet Reg Health West Pac, 2021 May;10:100126.
PMID: 34327343 DOI: 10.1016/j.lanwpc.2021.100126

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients.
Methods: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated.
Findings: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another.
Interpretation: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used.
Funding: Samsung Biomedical Research Institute.
Cutaneous T-cell lymphoma in Asian patients: a multinational, multicenter, prospective registry study in Asia

Lee YP, Yoon SE, Song Y, Kim SJ, Yoon DH, Chen TY, et al.

Int J Hematol, 2021 Sep;114(3):355-362.
PMID: 34302593 DOI: 10.1007/s12185-021-03179-7

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.