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Discovery of DYRK1A inhibitors as potential treatment of pancreatic ductal adenocarcinoma (PDAC)
No full text[[abstract]]Dual-specificity tyrosine phosphorylation-regulated kinase 1A(DYRK1A) belongs to the CMGC family of eukaryotic protein kinases and is an attractive therpaeutic target due to its roles in both neurodegenerative diseases and cancers. Based on the activity of DYRK1A interactors and substrates, it is assumed that DYRK1A is a pleiotropic protein with widespread cellular functions, including the regulation of cell proliferation, survival , and differentiation. In a recent study, DYRK1A was shown to be upregulated in pancreatic ductal adenocarcinoma (PDAC), providing evidence that DYRK1A favours tumour progression. in a PANC-1-shDYRK1A xenograft animal model, reduced levels of DYRK1A impaired proliferation, leading to slower tumour progression. These results prompted the discovery of DYRK1A inhibitors for the treatment of PDAC. In this study, we designed and synthesized a series of DYRK1A inhibitors. The structure-activity relationship (SAR) study results showed that PANDK103 eshibited excellent DYRK1A inhibitory ability with an IC50 value of 7.8nM, 40-fold greater than INDY, the known reference compound. Currently, we have achieved acceptable pharmacokinetic data. Further hit-to-ead optimization and pharmacokinetics studies are in progress and will be reported in due course
Comparative evaluation of sensititre YeastOne and VITEK2 antifungal susceptibility tests with CLSI broth microdilution method of clinical Cryptococcus isolates in Taiwan
No full text[[abstract]]Commercial antifungal susceptibility tests were available for clinical yeast isolates. However, the updated Sensititre YeastOne (SYO) version YO10C excluded Cryptococcus species for susceptibility testing. Uncorrelation of antifungal susceptibility patterns by SYO and therapeutic outcomes had been recently reported. We compared the performance of current commercial susceptibility tests with the standard CLSI broth microdilution (BMD) method for clinical Cryptococcus isolates. Forty-seven clinical Cryptococcus isolates were included from 1 January 2012 to 30 June 2023, among which 44 isolates were Cryptococcus neoformans while 3 were Cryptococcus gattii. The performance of SYO version YO10C and VITEK2 YS09 was compared with the CLSI BMD method and correlated with MLST analysis and ERG11 mutation detection. Non-wild- type (non-WT) strains to amphotericin B (AMB) were observed in 11 isolates with the CLSI BMD method and 8 with SYO among 44 C . neoformans isolates, but only 1 isolate was classified as non-WT by both methods. Additionally, all C. neoformans isolates were susceptible to AMB with their MIC 90% to most antifungal agents except ITC in C. neoformans isolates (64%) and AMB in C. gattii group (67%). Between SYO and CLSI BMD, the major error (ME) rates were 11% (n = 5) to FLC, 5% (n = 2) to ITC, and 2% (n = 1) to 5FC in C. neoformans isolates, and the very major error to 5FC was found in one C. gattii isolate. ERG11 mutation with identical I199V was detected in 89% (n = 39) C. neoformans isolates, and 97% (n = 38) of them belonged to sequence type (ST) 5. The ERG11 mutation or cryptococcal ST was not associated with a decrease of antifungal susceptibilities. ME of FLC by SYO version YO10C compared to the CLSI BMD method reached up to 11% of C. neoformans isolates. The results of FLC MIC by SYO should be interpreted cautiously and correlated with therapeutic response, and further verification with the CLSI BMD method or VITEK2 is required. IMPORTANCE The study pointed out the major errors of fluconazole susceptibility results in clinical Cryptococcus neoformans isolates between the commercial Sensititre YeastOne Susceptibility Plate version YO10C and the standard CLSI broth microdilution method. The results should be interpreted carefully with clinical correlation, and a different method of antifungal susceptibility testing should be considered if a discrepancy of susceptibility results is suspected
Cumulative risk assessment and exposure characteristics of parabens in a representative Taiwanese population
No full text[[abstract]]Parabens, widely used in consumer products, have been detected in various environmental media, particularly in significant amounts in indoor dust. This study evaluated urinary paraben levels and cumulative health risks in a representative Taiwanese population. Median urinary levels of MeP, EtP, PrP, and BuP varied by age and sex. Health risk assessment using the Hazard Index (HI) indicated a generally low risk for combined exposure to MeP and EtP. However, at the 95th percentile, daily intake of these parabens minimally contributed to the HI, with PrP displaying the highest individual risk. Over half of the participants had an HI exceeding 1, emphasizing significant exposure risks to parabens in the Taiwanese population. These findings highlight the importance of understanding paraben exposure patterns and associated health risks in this demographic
[[alternative]]Correction to:Identification of the novel tumor suppressor role of focad/mir-491-5p to inhibit cancer stemness, drug resistance and metastasis via regulating rabif/mmp signaling in triple negative breast cancer (Cells, (2021), 10, 10, (2524), 10.3390/cel
No full text[[abstract]]In the original publication [1], there was a mistake in Figure 5 as published. The original Figure 5G has accidentally re-planted the Figure 3E (sh-FOCAD group) image files. The corrected Figure 5 appears below. The authors stated that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated
プロテインキナーゼ阻害剤としてのアミノチアゾール化合物
No full text[[abstract]]Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the aminothiazole compounds
Compuestos de aminotiazol como inhibidores de la proteina quinasa
No full text[[abstract]]Se describen compuestos de aminotiazol de la Fórmula (I) que se muestran a continuación y las composiciones farmacéuticas que contienen uno de tales compuestos: (ver Fórmula) También se describen métodos para inhibir una tirosina quinasa y tratar el cáncer asociado con una tirosina quinasa con uno de los compuestos de aminotiazol
[[alternative]]Heterodimeric vascular endothelial growth factor and use thereof
No full text[[abstract]]本發明係關於一種融合蛋白，包含：(i)第一血管內皮生長因子同功異形體，與(ii)第二血管內皮生長因子同功異形體，及(iii)介於該第一同功異形體與該第二同功異形體間的雙聚化功能域，其中該第一同功異形體及該第二同功異形體係選自VEGF121及VEGF165
[[alternative]]Assembly teaching aid and electronic device thereof in immunology
No full text[[abstract]]免疫学の原理,特に抗体の構造および抗原と抗体の特異的結合のメカニズムを示すかまたは学習するための組み合わせ式教具および電子装置を提供する.【解決手段】抗体1の重鎖を示すための長柱10と,抗体の軽鎖を示すための短柱11と,病原体または細胞を示すための,表面に複数の挿入孔22を有する半球体ベース21と,挿入ピン部31と頭部32とを有し,該病原体または該細胞の表面分子を示すための嵌め込み部材3と,を備えた,免疫学の原理をデモンストレーションするための組み合わせ式教具2であって,当該教具は,科学普及教育,教員研修,展示,ゲーム,家庭での娯楽など各種状況に応用可能である
Microfluidic hydrodynamic shuttling chip device for highthroughput multiple single cells capture
No full text[[abstract]]A hydrodynamic shuttling chip device comprising an array of single-cell trapping units is disclosed. Each unit comprises: (a) an incoming channel with a cell capture site; (b) a cell culture chamber located posterior to the cell capture site, having a receiving site spaced apart from the cell capture site at a distance of g; (c) a trapping channel located between the cell capture site and the receiving site; (d) a chamber channel located posterior to and in fluidic connection with the cell culture chamber; and (e) a by-pass channel, located lateral to the incoming channel, chamber and chamber channel and having a first end and a second end opposite to the first end, the first end branching out from the incoming channel immediately prior to the cell capture site and the second end joining the chamber channel. A method of capturing single cells of more than one type is also disclosed
サブナノメートルの金展着剤およびそれによるエンドトキシン誘発性敗血症予防方法
No full text[[abstract]]A sub-nanometer gold sticker for blocking efficiently endotoxin activity to protect against sepsis is disclosed. The sub-nanometer gold sticker comprises a gold nanocluster that serves as a flake-like substrate and a coating of short alkyl motifs that act as an adhesive, allowing the sub-nanometer gold sticker to dock with LPS by compacting the intramolecular hydrocarbon chain-chain distance (d-spacing) of lipid A, an endotoxicity active site that can cause overwhelming cytokine induction resulting in sepsis progression. Methods of blocking endotoxin activity, and suppressing pro-inflammatory cytokines are also disclosed. Also disclosed is a method of protecting against endotoxin-induced sepsis via increasing critical micelle concentration for the inhibition of LPS non-lamellar aggregation