Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis

Ying Yang,Dong Wang,Lei Cui,Hong-Hao Ma,Li Zhang,Hong-Yun Lian,Qing Zhang,Xiao-Xi Zhao,Li-Ping Zhang,Yun-Ze Zhao,Na Li,Tian-You Wang,Zhi-Gang Li,Rui Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Identification of AMPK activator from twelve pure compounds isolated from Aralia Taibaiensis: implication in antihyperglycemic and hypolipidemic activities

Li, Yuwen,Park, Jongsun,Wu, Yin,Cui, Jia,Jia, Na,Xi, Miaomiao,Wen, Aidong The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

The root bark extract of Aralia taibaiensis is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from Aralia Taibaiensis (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-${\beta}$-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

Digital Economy Corporate Innovation and Corporate Finance Capabilities

Li, Na,Liu, Ziyang,Zhang, Xi 한국콘텐츠산업학회 2023 콘텐츠와 산업 Vol.5 No.2

The digital economy is a new driving force for China's high-quality economic development. Fully releasing the digital economy dividend to promote the innovation and development of the real economy is an important channel to realize the high-quality development of China's economy. This paper empirically analyzes the impact of digital economy development on enterprise equity financing and equity financing and its intrinsic mechanism of action based on the use of principal component analysis to construct an indicator system for the level of digital economy development at the provincial level in China, using sample data of A-share listed companies from 2013 to 2021. The research results show that: firstly, digital economy development can significantly enhance the equity financing and debt financing ability of enterprises, and the promotion effect on debt financing is more significant. Secondly, in terms of the influence mechanism, digital economy development can enhance corporate financing by improving the level of corporate innovation, which in turn affects the comprehensive strength and internal resources of enterprises. In the context of the rapid development of the digital economy, the combination of the digital economy and the real economy should be actively promoted, the innovation dividend of the digital economy should be fully released, and the role of the digital economy in promoting the level of corporate financing should be brought into play to promote high-quality economic development.

Identification of AMPK activator from twelve pure compounds isolated from <i>Aralia Taibaiensis</i>: implication in antihyperglycemic and hypolipidemic activities

Yuwen Li,Jongsun Park,Yin Wu,Jia Cui,Na Jia,Miaomiao Xi,Aidong Wen 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

The root bark extract of <i>Aralia taibaiensis</i> is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from <i>Aralia Taibaiensis</i> (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-β-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

Identification of AMPK activator from twelve pure compounds isolated from Aralia Taibaiensis: implication in antihyperglycemic and hypolipidemic activities

Yuwen Li,박종선,Yin Wu,Jia Cui,Na Jia,Miaomiao Xi,Aidong Wen 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.3

The root bark extract of Aralia taibaiensis is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from Aralia Taibaiensis (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-β-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

Willingness to Continue Using Knowledge Payment Products Based on Information Adoption Model: The Intermediary Role of Customer Engagement

Zhang, Xi,Liu, Ziyang,Li, Na 한국비즈니스학회 2023 비즈니스융복합연구 Vol.8 No.3

Knowledge payment is an important form of sharing economy. Research on the continuous use willingness of knowledge payment consumers will help to realize the sustainable development of the knowledge payment industry. Based on the information adoption model and the customer engagement theory, the function model of consumers' willingness to continue using knowledge payment is constructed. Data are collected through the questionnaire star platform, and the model and hypothesis are tested by SPSS23.0 and AMOS24.0. The results show that information quality and credibility of information sources have significant positive effects on customer psychological engagement and behavioral engagement; Customer engagement has a significant positive impact on the willingness to continue using knowledge payment; Customer engagement plays an intermediary role between the quality of information and the credibility of information sources and the willingness to pay for continuous use of knowledge. This study emphasizes the importance of information quality, credibility of information sources and customer engagement in influencing consumers' willingness to continue using knowledge payment products, and provides some reference for the knowledge payment platform to develop effective online marketing strategies.

Dryland agricultural environment and sustainable productivity

Gou-Xia Li,Bing-Cheng Xu,Li-Na Yin,Shi-Wen Wang,Sui-Qi Zhang,Lun Shan,곽상수,Qingbo Ke,Xi-Ping Deng 한국식물생명공학회 2020 Plant biotechnology reports Vol.14 No.2

Global climate change is expected to cause progressively increased frequency and severity of drought events, which further seriously limit plant growth and crop yields. Increasing water use effi ciency (WUE) and yield per unit rainfall are one of the most important challenges in dry land agriculture. Here, we reviewed the comprehensive technical strategies including conserving water to combine both increased agricultural productivity and resource conservation; enquiring into how crop plants respond to drought through morphological, physiological, and molecular modifi cations that occur in all plant organs; breeding for drought tolerance where there is a delineated stress environment and genotype × environment interactions are stable; eff ective conservation of rainfall and high effi ciency of use. In addition, we discussed the preponderance of biological water-saving measures, which embraces improvements in WUE and drought tolerance, by genetic improvement and physiological regulation. Sustainable agriculture would be benefi ted from modern engineering such as biological engineering, conservation tillage, and breeding technologies.

NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria

Wu, Cheng-zhe,Li, Xiang,Hong, Lan,Han, Zhuo-na,Liu, Ying,Wei, Cheng-xi,Cui, Xun The Korean Society of Pharmacology 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.2

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 μM) and BQ788 (0.3 μM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 μM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 μM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxia-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 μM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 μM) and LY294002 (10.0 μM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Inhibition of RIPK1-dependent regulated acinar cell necrosis provides protection against acute pancreatitis via the RIPK1/NF- κB/AQP8 pathway

Gang Wang,Peng-yu Duan,Yuan Ma,Xi-na Li,Feng-zhi Qu,Liang Ji,Xiao-yu Guo,Wang-jun Zhang,Fan Xiao,Le Li,Ji-sheng Hu,Bei Sun 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Currently, preliminary results have confirmed the existence of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL)-dependent necroptosis of pancreatic acinar cells during early acute pancreatitis (AP), which might be a potential target for the effective regulation of necroinflammatory injury. However, the exact effect of receptor-interacting protein kinase 1 (RIPK1)-dependent regulated acinar cell necrosis on AP is still uncertain. In our study, we first explored the changes in the degree of local and systemic inflammation in AP rats when the activation of acinar cell RIPK1 was inhibited. The RIPK1 inhibitor Nec-1 was used to treat rats, and the levels of related inflammatory markers, necrosis indicators and apoptotic indicators were measured. Changes in pancreatic nuclear factor κB (NF-κB) and aquaporin 8 (AQP8) expression were noted. Next, the expression of AQP8 in AR42J cells was inhibited, and the degree of cell necrosis and inflammatory damage was found to be significantly reduced. Most importantly, we demonstrated that the RIPK1/NF-ĸB/AQP8 axis might be a potential regulatory pathway mediating RIPK1-dependent regulated acinar cell necrosis in early AP. Finally, we used the NF-κB inhibitor PDTC and Nec-1 to treat rats in different groups and measured the degree of pathological pancreatic injury, the activation of RIPK1, and the expression of NF-κB and AQP8. In summary, we hypothesized that there might be a RIPK1/NF-ĸB/AQP8 pathway controlling RIPK1-dependent regulated necrosis of acinar cells in AP, which might be a promising therapeutic target against AP-related injury.

An Aqueous Extract of Yunnan Baiyao Inhibits the Quorum-Sensing-Related Virulence of Pseudomonas aeruginosa

Zu-Guo Zhao,Shuang-Shuang Yan,Yun-Mei Yu,Na Mi,La-Xi Zhang,Jun Liu,Xiao-Ling Li,Fang Liu,Jun-Fa Xu,Wei-Qing Yang,Guo-Ming Li 한국미생물학회 2013 The journal of microbiology Vol.51 No.2

Yunnan Baiyao is a famous Chinese medicine that has long been directly applied to wounds to reduce bleeding, pain, and swelling without causing infection. However, little is known about its ability to prevent infection. The present study aimed to assess in vitro the anti-virulence activity of an aqueous extract of Yunnan Baiyao (YBX) using Pseudomonas aeruginosa as a pathogenic model. We found that a sub-MIC (2.5 mg/ml) of YBX can efficiently interfere with the quorum-sensing (QS) signaling circuit. Real-time polymerase chain reaction analysis showed that a sub-MIC of YBX downregulated the transcriptions of lasR, lasI, rhlR, and rhlI,which resulted in global attenuation of QS-regulated virulence activities, such as biofilm formation, and secretion of LasA protease, LasB elastase and pyocyanin. Further, YBX reduced the motility of P. aeruginosa related to QS, and impaired the formation of biofilms. These results suggest that YBX may possess global inhibitory activity against the virulence of P. aeruginosa and that YBX may also exhibit antimicrobial activity in vivo. The present study suggests that Yunnan Baiyao represents a potential source for isolating novel, safe, and efficacious antimicrobial agents.