bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk assessment of GMP inspection of overseas pharmaceutical manufacturers based on pic/s desktop inspection
Authors:   , Cheewajorn Waranon 
Published: September 2023

Good manufacturing practice (GMP) inspection of overseas manufacturers is regulated under desktop inspection by Thailand Food and Drug Administration (Thai FDA). The desktop inspection system is verified mainly by document without on-site inspection like for local manufacturers. The inspection results may thus cause certain gaps in terms of quality and reliability. In addition, none has reported the risk assessment of desktop inspection system in Thailand and the limited research articles investigated these gaps. This work utilized the quality risk management (QRM) of International Council for Harmonization Q9 (ICH Q9) guideline with Failure Mode and Effects Analysis (FMEA) tool to study risk assessment and risk control of GMP desktop inspection system of overseas pharmaceutical manufacturers in Thailand. The study design consisted of 5 steps. First, pre-assessment step was to set up a risk assessment team and data analysis of desktop inspection and drug quality defect situation over three years in 2016 – 2018. Next, risk identification step was performed by analysis of regulation gap and routine workflow. The regulation gap was analyzed by comparing Thai regulations against five globally-selected countries/organizations, namely; Singapore, Malaysia, Australia, World Health Organization (WHO) and The Pharmaceutical Inspection Co-operation Scheme (PIC/S). Followed by risk analysis and risk evaluation step, brainstorming based on team discussion, along with using FMEA tool and risk priority number (RPN) were conducted. Finally, risk reduction step described all the risk mitigation approaches, verified by implementation and re-assessment. The results showed that the most potential negative effects on the quality and reliability of the desktop inspection system with highest RPN values were desktop inspection pathway for non-PIC/S or non-WHO prequalification certified manufacturers (RPN = 100) and lack of stepwise approach in document review (RPN = 80) that were analyzed as the high-risk level based on the regulation gap and workflow analysis, respectively. Such overseas manufacturers tended to have various GMP standards based on their own quality system criteria and be inspected by different levels of the authorized inspectorate. Meanwhiles, lack of this stepwise can lead to missing critical points and difference in inspection results. Nevertheless, after implementation, stepwise procedures justified the quality of inspection results and reduced RPN value and risk level to acceptable level. This work can be very useful for the Thai FDA to manage and minimize all potential risks for continual quality improvement of the desktop inspection system for overseas pharmaceutical manufacturers in Thailand.
Serum non-coding RNA levels as potential diagnostic and prognostic markers of hepatocellular carcinoma
Authors:   , Pratedrat Pornpitra 
Published: September 2023

Hepatocellular carcinoma (HCC) is one of the most common type of liver cancers in the world. Most common cause of HCC is viral hepatitis B infection (HBV). That lead to HCC detection at late stage and be difficult for curative treatment. So, biomarkers for HCC are required to detect HCC efficiently. MicroRNAs and long non-coding RNAs (lncRNAs) play a key role in tumorigenesis through many different mechanisms. Moreover, non-coding RNA can be released into body fluid. Hence purpose of this study is to investigate the level of miRNA and lncRNAs in serum as the used as potential biomarkers for HBV-HCC detection. For miRNAs, miRNA-223-3p can be determined as an independent factor for predicting overall survival rate in patients with HCC-HBV. Therefore, miR-223-3p might be a novel potential miRNA for HCC prognosis. Another lncRNAs, circulating H19 can be used with AFP to increase both sensitivity and specificity for HCC prediction. We further studied the relation between H19 and cancer phenotypes by gene knock out via CRISPR/Cas9. The result showed that silenced H19 can decrease cell migration in Huh7 (p < 0.05). According to the complication of lncRNA functions in cell, it is difficult to conclude the main mechanism of lncRNA to predict the disease progression, and cannot use specific lncRNA alone for disease marker. Therefore, the use of combination marker types may help to improve predictive values for diseases progression. However, a large cohort is required for serum validation.
"Bricks in the wall" : sufficiency economy philosophy in Thailand and gaps in the framework
Authors:   , Takenaka Laura 
Published: September 2023

His Majesty King Bumibol Adulyadej was inspired by a book called Small is Beautiful, all about how to humanize economics and make development benefit those who need it most. When he saw the devastation after the 1997 Asian Economic Crisis, he formulated the Sufficiency Economy Philosophy (SEP) to help the Thai people recover and to make Thailand more resilient. The purpose of this thesis is to examine the philosophy in depth and find the gaps in the framework. The objectives are to pinpoint the gaps and weaknesses in the current framework, obtain farmers’ insights into the realities of farming via the New Theory, and analyse the feasibility of large corporations using SEP for their internal management. Critical indicators for agribusiness and non-agricultural based businesses are identified. They are the ‘bricks’ of Indicators (operational applications) and a new finding of Democratization. For large corporations, Democratization may not be possible, but the SEP theory could be more flexible in interpretation, such as cooperation could be introduced in stages as a compromise. The Thai Government is promoting the SEP as the vehicle to achieve the United Nations Global Goals. If the SEP is applied both domestically and internationally by the Thai Government, it could achieve the SDG’s Goals 1, 2, 5, and 10. A qualitative study comprised of a comprehensive literature review, a series of participant interviews, participant observation on SEP New Theory farms and research sites as well as speaking to key informants outlined the situation of the New Theory farmer. A macro view of six business case studies of corporations that are said to be SEP compliant were conducted with data analysis and online research as well as email interviews between the researcher and relevant stakeholders.
Korean education policy and parents expectation: case study of Korean school in Thailand
Authors:   , Luewiphan Piranun 
Published: September 2023

Korean education policy had established Korean schools or KS for expatriated Korean in many countries including in Thailand. The purposes of this study are 1) to understand the characteristic of KS in terms of schools established aboard with the Korean curriculum base. 2) To understand the purpose and expectations of parents on the Korean School and see if those expectations are met. The data was collected by survey all related parties of the Korean International School (Students, teachers, and parents) 69 respondents. The data were collected from June – August 2020. The study shows that not only the Korean Government creates KS that uses the Korean core curriculum to provide the same standard education as the private school in South Korea but also wants to help students maintain their identity as Korean. We find that the students show more favoritism and comfortable over Korean culture, furthermore around 68% of the student wants to live in Korea after graduation. And the second result shows that KS parents’ expectation on KS can be divided into two groups, first the elementary level parents who seek for the good school system and trusted environment for their child to study, and the secondary level parents who are more focused on getting privilege opportunity to get into good university from residing in Thailand.
ICT development and wage premiums across countries
Authors:   , Dai Hongwu 
Published: September 2023

This study examines the effect of ICT on wage premium, by using data from 64 countries during the period 2010–2016. The Fixed Effect Model (FEM) is employed to study the relationship between ICT development and income inequality, by using two dependent variables: the conventional wage premium and wage premiums for ICT-intensive occupation. The main findings are: 1) the wage premium in countries with low levels of ICT development is relatively higher; 2) the development of ICT has a positive relationship with the wage premium; 3) the roles of the three sub-indexes of ICT development are different: ICT access shows a small positive relationship, while ICT use and ICT skills are significantly negative with the wage premium.

However, the results of the split sample provide a different result. The development of ICT has a negative relationship with the wage premium in higher ICT developed countries.
The effect of 1’ acetoxychavicol acetate on cell proliferation, metastasis, and angiogenesis in human endocrine-resistant breast cancer cells
Authors:   , Pradubyat Nalinee 
Published: September 2023

Background: Oestrogen receptor (ER)-positive breast cancer patients have a good prognosis, but 30% of these developed resistance through hyperactivation of PI3K/AKT, ERK1/2, and NFκB, which interconnected with ER signalling. In this study, the effects of 1’ acetoxychavicol acetate (ACA), a plant-metabolite acetate ester compound with an NF-kB inhibitory activity, were investigated in a panel of endocrine-resistant breast cancer cells.

Methods: Plant material was purified by chromatographic methods and followed by structural identification using nuclear magnetic resonance and mass spectroscopy. In vitro and in vivo antiproliferative effects of ACA were studied in MCF7/LCC2 and MCF7/LCC9 endocrine-resistant cells using the MTT assay and the zebrafish xenograft model respectively. Anti-invasion of ACA was performed by the matrigel invasion assay, while its mechanism of action was elucidated through molecular docking simulation, real-time PCR, and western blotting. Western blot analysis was also used to investigate its effect on apoptosis.

Results: ACA inhibited the proliferation of MCF7, MCF7/LCC2, and MCF7/LCC9 cells at a concentration- and time-dependent fashion. This was associated with down-regulation of HER2 receptor, estrogen receptor coactivator (NCOA3), pERK1/2, pAKT, and proliferative markers (CCND1, C-myc). While in vivo, significant reduction in the tumour mass of ACA-treated zebrafish engrafted MCF7/LCC9 groups was observed compared to the control treatment. Furthermore, the anti-invasive effects of ACA were confirmed in vitro by the matrigel invasion assay and with reduction in the expression levels of CXCR4, uPA and proangiogenic factors, VEGF and FGF2 in ACA-treated cells compared to untreated control. The repressed expression of uPA and FGF2 was also validated by molecular docking analysis. Moreover, ACA-treated cells exhibited lower expression levels of the anti-apoptotic BCL2 and MCL1 proteins in addition to increase JNK/SAPK expression and enhance PARP cleavage, indicating apoptotic cell induction by ACA.

Conclusion: This research suggested that the ACA inhibited cell proliferation and induce apoptosis in breast cancer cells through HER2/MAPK/ERK1/2 and PI3K/AKT pathways. In addition, the anti-angiogenic and anti-invasive activity of ACA was through the downregulation of VEGF, FGF2, uPA, and CXCR4.
Uniform distribution of fractional parts of average of kth power of prime divisors
Authors:   , Chairatanagul Chitpanu 
Published: September 2023

In this thesis, we prove that for every positive integer k greater than or equal to two, the sequence of the fractional parts of the arithmetic mean of the kth power of prime divisors of n counted with or without multiplicity, as n runs through all positive integers, is uniformly distributed modulo one.
Functional and transcriptomic changes in synergy of endotoxin and (1->3)-β-D-glucan in bone marrow derived macrophage from Fc gamma receptor IIb deficient mice
Authors:   , Issara-amphorn Jiraphorn 
Published: September 2023

Systemic lupus erythematosus (SLE) is an autoimmune disease with a diverse array of clinical symptoms. There are many factors including environmental factors may trigger disease progression. In this study, we investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in Fc gamma receptor IIb deficient (FcgRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively. The spontaneous gut leakage as determined by i) the level of serum FITC-dextran, ii) increased serum endotoxin (LPS), and iii) increased serum (1->3)-b-D-glucan (BG), were demonstrated in symptomatic FcgRIIb-/- mice, but not in asymptomatic group. Moreover, spontaneous gut leakage was detected by increased serum BG without fungal infection was also found in SLE patients with lupus nephritis. Gut leakage induced by dextran sulfate solution (DSS) or LPS injection with BG or LPS alone, but not BG alone, enhanced the severity of cecal ligation and puncture (CLP) sepsis more prominently in 8-week-old FcgRIIb-/- mice. In addition, BG+LPS activated FcgRIIb-/- macrophages produced higher level of proinflammatory cytokine when compared with wild type macrophage. Moreover, BG+LPS activated macrophages enhanced expression of activating FcgRs, NF-kB and Syk compared with wild type macrophage. The inhibitor against Dectin-1, Syk and NF-kB, but not Raf-1, reduced supernatant TNF-α in BG+LPS activated macrophages implying Syk dependent signaling. Additionally, Syk abundance in FcgRIIb-/- mice and in CLP surgery were higher than wild type mice possibly due to several Syk-activator (anti-dsDNA, LPS and BG), and Syk inhibitor attenuated proteinuria and serum cytokine only in FcgRIIb-/- mice. Moreover, administration of a Syk inhibitor prior CLP surgery in FcgRIIb-/- mice attenuated sepsis severity as evaluated by mortality, organ injury, Serum LPS and post serum cytokines. Furthermore, RNA sequencing analysis of BG+LPS activated macrophages with or without Syk inhibitor treatment, we found that Syk inhibitor downregulated several inflammatory pathways in macropahges, suggesting the potential anti-inflamatory impact of Syk inhibitor in lupus. The genes that found in BG+LPS activated macrophages associated with the prediction of genes involve in mortality in sepsis patients and Syk inhibitor treatment reversed almost direction of those genes.

In conclusion, spontaneous gut leakage and the induction of gut permeability worsened sepsis severity. Gut translocation of LPS and BG showed minor effect on wild type mice, but the synergistic effect of BG and LPS was prominent in FcgRIIb-/- mice, suggesting the therapeutic strategies addressing gut leakage may be interest in sepsis condition in patient with sepsis. In addition, Syk signaling is promising therapeutic target for SLE patients. Syk inhibitor appears to be an alternative drug for treatment of lupus with a counter on sepsis.
The effect of a trehalase inhibitor, validamycin A, on the growth of Aspergillus flavus
Authors:   , Plabutong Napasawan 
Published: September 2023

Aspergillus flavus is a fungus found in the environment causing keratitis, cutaneous infections, sinusitis, invasive pulmonary aspergillosis in humans. Although this fungus can be treated with antifungal agents, these main antifungal agents have many side effects. Trehalase is an enzyme for digesting trehalose into two glucose subunits and is essential for virulence in many fungi. A trehalase inhibitor, called validamycin A, has been used effectively against a rice fungal pathogen, Rhizoctonia solani. In this study, we observed that validamycin A increased trehalose levels significantly in A. flavus spores and delayed the germination of those spores. In addition, to further investigate the combinative effect of validamycin A with an antifungal agent, amphotericin B, the checkerboard assay was performed with A. flavus ATCC204304 and A. flavus clinical isolates with high minimum inhibitory concentrations (MICs) of amphotericin B. We observed that validamycin A and amphotericin B had a synergistic effect with these A. flavus clinical isolates. The cytotoxicity of validamycin A to human bronchial epithelial cells was not observed in this study. In conclusion, this study showed that validamycin A was able to inhibit the growth of A. flavus. One of the mechanisms behind the effect of validamycin A was to delay the germination of A. flavus spores. Furthermore, validamycin A also possessed a combinative effect with amphotericin B without significant cytotoxic effect on human bronchial epithelial cells.
Characterization of MAIT TCR repertoire of gastrointestinal tract and peripheral blood MAIT cells
Authors:   , Kongkaew Thidarat 
Published: September 2023

Mucosal-associated invariant T (MAIT) cells are an innate-like T cell that rapidly respond to infection. MAIT cells are αβ T cells that possess a Vα7.2 (TRAV1-2) TCR with mostly pairing to TRAJ33, TRAJ20 or TRAJ12 and predominantly TRBV20-1, TRBV6-1 and TRBV6-4. MAIT T cell receptors (TCR) repertoire have been previously studied in peripheral blood. However, data on MAIT TCR repertoire in gastrointestinal tract are lacking. We studied 2 individuals who are underwent esophagogastroduodenoscopy (EGD) and colonoscopy. Blood and biopsies were obtained. PBMCs were isolated from blood and LPLs were isolated from biopsies. Due to the low number of MAIT cells in each gastrointestinal tract site and being insufficient for experiments, we proliferated MAIT cells to increase MAIT cell population. Our results show that MAIT cells can proliferate in vitro. We mostly found TRAJ33 followed by TRAJ20, TRAJ12 that contained Tyr95, which necessary for interaction with antigens and TRAJ30 and TRAJ36, which contained Arg95 and Asn95 that also interact with antigens. Moreover, most TRBV gene usage in every site were TRBV6-4 and TRBV20-1. There were overlapping and non-overlapping TRBV gene usage in each site. The TRBV in ileum of both patients was the most diverse. We may concluded that MAIT TCR repertoire in mucosal was more diverse than peripheral and the result of MAIT TCR repertoire may concluded that MAIT TCR repertoire are associate with bacterial selection. However, the study of vitamin B metabolite synthesis bacteria may be help us to more understand MAIT TCR selection.
Polyvinyl alcohol/starch modified cotton thread for glucose distance-based colorimetric detection
Authors:   , Punnoy Pornchanok 
Published: September 2023

In this thesis, polyvinyl alcohol (PVA) and starch modified cotton thread was developed as a cotton thread-based device for distance-based colorimetric detection of hydrogen peroxide (H2O2) and glucose. PVA and starch, the biocompatible polymers, were modified on a cotton thread to enhance the enzymatic stability and reagent immobilization efficiency. The colorimetric glucose detection of the device was based on a bienzymatic reaction involving glucose oxidase (GOx) and horseradish peroxidase (HRP), incorporated with potassium iodide (KI) as an indicator, which was oxidized by H2O2 to provide blue-black color band of an iodine–starch complex. The length of color band on the cotton thread is proportional to H2O2 and glucose concentrations, allowing for a simple and rapid quantitative detection observed by the naked eyes without any signal readout instrument. For the best performance of the proposed device, various parameters were studied, such as the ratio of PVA/starch, KI volume, HRP volume and sample volume. Under the optimal conditions, the cotton thread-based device was used to detect H2O2 and glucose providing linear ranges of 1.0-6.0 mM and 0.1-5.0 mM with detection limits of 0.25 mM and 0.1 mM, respectively. Furthermore, the interference effect of glucose detection was also investigated and the obtained results showed no interfering from common compounds in human tear (i.e. potassium chloride, sodium chloride, urea, ascorbic acid, uric acid, cholesterol and bovine serum albumin). Eventually, the developed device could be successfully applied for the quantitative determination of glucose in artificial human tear.
In vitro antiplatelet activity of lusianthridin in human platelets
Authors:   , Swe Hla 
Published: September 2023

Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. The objective of this study is to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. Turbidometric aggregometry method was used to measure the extent of platelet aggregation, then cyclic adenosine monophosphate (cAMP) levels were measured by ELISA kit. Inhibitory effect of lusianthridin on cyclooxygenase enzymes was analyzed by COX fluorescent inhibitor screening assay kit. The results indicated that Lusianthridin most potently inhibited arachidonic acid -induced platelet aggregation by maximum percent inhibition of aggregation of 89.7 ± 1.2 % at 0.025 mM; whereas lusianthridin at 0.4 mM inhibited collagen and ADP-induced platelet aggregation by 84.5 ± 2.2 % and 51.9 ± 4.8 %, respectively. Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated aggregations. Lusianthridin showed the inhibitory effect on the secondary wave of ADP-stimulated aggregation. Furthermore lusianthridin at 0.4 mM inhibited ADP-induced by significantly increase cAMP level in platelets (p < 0.05). Molecular docking analysis revealed that lusianthridin bound to the entrance site of cyclooxygenase -1 (COX-1) enzyme and probably the active region of COX-2 enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities with the IC50 value of 11.92 ± 0.00 µM and 0.21 ± 0.17 µM, respectively. These findings suggested that possible mechanisms of lusianthridin on antiplatelet activity might act via arachidonic acid-thromboxane and ADP-adenylate cyclase pathways.
DNA barcoding coupled with high resolution melting (BAR-HRM) analysis for differentiation white kwao khruea (pueraria candollei), black kwao khruea (mucuna macrocarpa), and red kwao khruea (butea superba)
Authors:   , Vejpanich Nonthapon 
Published: September 2023

Kwao Khruea is the herbal product that known as a rejuvenation herb. In Thai traditional medicine, three species of Kwao Khruea including white Kwao Khruea (Pueraria candollei Wall. ex Benth.), black Kwao Khruea (Mucuna macrocarpa Wall.) and red Kwao Khruea (Butea superba Roxb. ex Willd.) have been used. Each Kwao Khruea accumulates different chemical constituents. White Kwao Khruea contains estrogenic biological activities while black and red Kwao Khruea accumulate testosterone-like activities. Black Kwao Khruea was reported to be potent than red Kwao Khruea. Because of similar common names with the difference in chemical compositions of Kwao Khruea herbs, it is necessary to differentiate those herbs for efficiency and safety purposes. Therefore, this study aims to differentiate the herbal species using genetic information by barcoding of the four core DNA regions including matK gene, rbcL gene, psbA-trnH transgenic spacer and internal transcribed spacer (ITS). The result showed that all four core barcode regions can differentiate those three Kwao Khruea. In addition, DNA barcoding coupled with high resolution melting (Bar-HRM) analysis of the PCR amplicons by real-time PCR was performed to investigate a particular DNA sequence in the matK gene and ITS. The melting temperature (Tm) of PCR products amplified by matK gene of red, white and black Kwao Khruea were 73.6ºC, 74.7ºC and 74.8ºC, respectively while the Tm of PCR amplicons from the ITS were 88.1ºC, 85.6ºC and 84.5ºC, correspondingly. In conclusion, DNA barcode coupled with HRM analysis has been successful to identify Kwao Khruea species in dietary supplements and traditional medicines containing Kwao Khruea as the main mixture. Our developed method is potentially used for the authentication of Kwao Khruea products prior to registration.