Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia

Jun-Xia Wang,Miao-Miao Yang,Li-Peng Liu,Hui-Min Zhang,Meng-Chuan Wang,Yu-Wen Chen,Xiao-Ying Zang,Fang Hu 대한암학회 2023 Cancer Research and Treatment Vol.55 No.3

Purpose This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices.Materials and Methods Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated.Results Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia.Conclusion TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.

miR-1246 inhibits NFATc1 phosphorylation and regulates Th17 cell activation in the pathogenesis of severe alopecia areata

Si-si Qi,Ying Miao,You-yu Sheng,Rui-ming Hu,Jun Zhao,Qin-ping Yang 대한피부과학회 2023 Annals of Dermatology Vol.35 No.1

Background: We found microRNA (miR)-1246 to be significantly differentially expressedbetween severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ Tcells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistryassays. Peripheral CD4+ T cells from the AA patients were transfectedwith lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis wereused to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclearreceptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylatedNFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA wasused to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantlyincreased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cellsbut not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltratinginflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA,overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1,ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in theCD4+IL-17+ cells proportion and the IL-17F level. Conclusion: miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may bebeneficial in the severe AA treatment.

A native Trichoderma harzianum strain Th62 displays antagonistic activities against phytopathogenic fungi and promotes the growth of Celosia cristata

Yue-Feng Wang,Xue-Yue Hou,Chuan-Ying Jiang,Tong-Tong Zhai,Rui Miao,Jun-Jie Deng,Zhi-Hong Yao,Rongshu Zhang 한국원예학회 2021 Horticulture, Environment, and Biotechnology Vol.62 No.2

Trichoderma spp. are widely applied, eco-friendly mycofungicides and plant growth promoters. Native Trichoderma strainsare likely to have more productive, stable biocontrol and biofertilizer activities since they are well adapted to the local environment. In this study, we isolated a native Trichoderma strain ‘Th62’ from the rhizosphere soil of wild Chelidonium majusplants in Harbin, China (126.6341°E, 45.7242°N). The isolated Trichoderma strain was identifi ed as a T. harzianum strainvia morphological observation and molecular methods based on the rDNA internal transcribed spacer region and elongationfactor-1α gene sequences. Signifi cant antagonistic activities of Th62 against fi ve soil-borne fungal phytopathogens,Fusarium oxysporum , Sclerotinia sclerotiorum , Alternaria alternata , Cytospora chrysosperma, and Rhizoctonia solani ,were confi rmed by dual-culture assays. Furthermore, the crude fermentation products of Th62 also displayed antifungalactivities against these fi ve pathogens. To evaluate the function of Th62 as a biofertilizer, we subsequently applied Th62on cockscomb ( Celosia cristata L), a plant species with both ornamental and medicinal values, by inoculation with Th62conidia at diff erent concentrations, 1 × 10 10 cfu mL −1 , 1 × 10 11 cfu mL −1 , and 1 × 10 12 cfu mL −1 . The benefi cial eff ects ofTh62 were evaluated by measuring the growth and photosynthetic traits of the inoculated cockscomb plants, and the resultsdemonstrated that Th62 signifi cantly improved the photosynthetic effi ciency, photosynthetic capacity, and the adaptabilityto intense light of the inoculated cockscomb plants compared to the controls. Consistently, Th62 inoculation signifi cantlyimproved the growth and fl ower yield of cockscomb. We presented a positive case of isolating and applying native microbialresources on local plantation practices.

Highly Efficient Microwave-assisted Aminolysis of Epoxides in Water

Zuo, Hua,Li, Zhu-Bo,Zhao, Bao-Xiang,Miao, Jun-Ying,Meng, Li-Juan,Jang, Ki-Wan,Ahn, Chul-Jin,Lee, Dong-Ha,Shin, Dong-Soo Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.suppl8

Highly efficient and rapid aminolysis of epoxides with various amines in water under microwave irradiation in the absence of catalyst was developed. Chiral ${\beta}$-amino alcohols were formed in a short time with excellent yields.

Highly Efficient Microwave-assisted Aminolysis of Epoxides in Water

Hua Zuo,Zhu-Bo Li,Bao-Xiang Zhao,Jun-Ying Miao,Li-juan Meng,Kiwan Jang,안철진,Dong-Ha Lee,신동수 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.8

Highly efficient and rapid aminolysis of epoxides with various amines in water under microwave irradiation in the absence of catalyst was developed. Chiral β-amino alcohols were formed in a short time with excellent yields.

Design, Synthesis In Vitro Anticancer Activity and Docking Studies of (−)-Catechin Derivatives

Deepak Kumar,S. J. Harshavardhan,Sridhar Chirumarry,Y. Poornachandra,장기완,C. Ganesh Kumar,윤용진,Bao-Xiang Zhao,Jun-Ying Miao,신동수 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.2

Novel series of ()-catechin derivatives 1a-l were synthesized, characterized and assayed for their cytotoxicity against four selected human cancer cell lines by standard MTT assay method. Most of the compounds significantly active among which 1d exhibited promising activity with IC50 values of 2.5, 4.8 and 5.4 μM specifically against hepatocellular liver carcinoma (HepG2), lung adenocarcinoma (A549) and prostate (DU-145) cell lines, while compound 1j showed promising cytotoxicity against human breast adenocarcinoma MDA-MB-231 (IC50 value of 6.6 μM). Compounds 1a, 1d, 1e, 1f and 1j exhibited broad spectrum cytotoxicity against all the cell lines screened. Molecular docking studies of compound 1d established the good binding affinity and are in favor of the observed biological activity. These data collectively suggest that compound 1d could serve as a new template for further optimization as anticancer agent.