CircFam190a: a critical positive regulator of osteoclast differentiation via enhancement of the AKT1/HSP90β complex

Chen Kun,Chen Xi,Lang Chuandong,Yuan Xingshi,Huang Junming,Li Zhi,Xu Mingyou,Wu Kerong,Zhou Chenhe,Li Qidong,Zhu Chen,Liu Lianxin,Shang Xifu 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

The identification of key regulatory factors that control osteoclastogenesis is important. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the complexities of circRNA expression as well as the extent of their regulatory functions during osteoclastogenesis have yet to be revealed. Here, based on circular RNA sequencing data, we identified a circular RNA, circFam190a, as a critical regulator of osteoclast differentiation and function. During osteoclastogenesis, circFam190a is significantly upregulated. In vitro, circFam190a enhanced osteoclast formation and function. In vivo, overexpression of circFam190a induced significant bone loss, while knockdown of circFam190a prevented pathological bone loss in an ovariectomized (OVX) mouse osteoporosis model. Mechanistically, our data suggest that circFam90a enhances the binding of AKT1 and HSP90β, promoting AKT1 stability. Altogether, our findings highlight the critical role of circFam190a as a positive regulator of osteoclastogenesis, and targeting circFam190a might be a promising therapeutic strategy for treating pathological bone loss.

Primary-Side Control for Flyback Converter with Wide Range Operation

Bin-Kun Huang,Tsorng-Juu Liang,Wei-Jing Tseng,Kai-Hui Chen,Qing-Mu Chen 전력전자학회 2019 ICPE(ISPE)논문집 Vol.2019 No.5

Most of current primary side regulation (PSR) control methods are implemented in either discontinuous conduction mode (DCM) or continuous conduction mode (CCM). Because of the difficulty in sensing the output voltage, no algorithm is suitable for both DCM and CCM, and the power range of the system is limited. The proposed controller is suitable for both DCM and CCM with wide power range operation. The “TSMC 0.25 μm CMOS high voltage mixed signal process” is adopted to implement the proposed IC. A flyback converter with 400 V input and 20 V/150 W output is built to verify the feasibility of proposed control IC.

Mechanical Stretch Promotes Invasion of Lung Cancer Cells via Activation of Tumor Necrosis Factor-alpha

Liang-Kun Chen,Ching-Chi Hsieh,Yi-Chao Huang,Yuan-Jung Huang,Chun-Fan Lung,Wei-En Hsu,Chao-Ling Yao,Tsung-Yu Tseng,Chi-Chung Wang,Yi-Chiung Hsu 한국생물공학회 2023 Biotechnology and Bioprocess Engineering Vol.28 No.3

Most of the gas exchange in the human body is carried out by the lungs, and the physiological activities of the lungs are uninterrupted. Due to the deterioration of the external environment, pulmonary cell lesions are common clinical lung diseases. Mechanical cyclic stretching is one kind of bionic technology to observe lung cancer cells. The A549 cell line is the human lung adenocarcinoma cell line derived from a primary lung tumor. This study investigated the effects of mechanical cyclic stretching on A549 cell activity and gene expression profile. Whereas mechanical cyclic stretching had no significant difference in colony formation and cell migration of A549 cells, the cell invasion increased significantly in A549 cells after stretching. In addition, the microarray data showed that mechanical cyclic stretching altered gene expression, induced inflammation of cells, and activation of Wnt/β- catenin and tumor necrosis factor pathways. More importantly, mechanical cyclic stretching activated the expression of tumor necrosis factor-alpha (TNF-α) protein. Therefore, the increase of cell invasion induced by mechanical cyclic stretching might be associated with the activation of TNF-α in human lung adenocarcinoma cells.

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Chun-Shih Chin,Jeng-Sen Tseng,Tsung-Ying Yang,Kun-Chieh Chen,Kang-Yi Su,Sung-Liang Yu,Jeremy J.W. Chen,Gee-Chen Chang 대한암학회 2022 Cancer Research and Treatment Vol.54 No.2

Purpose The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients. PurposeThe aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.Materials and MethodsFrom August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.ResultsA total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).ConclusionOur research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced <i>EGFR</i>-mutant lung adenocarcinoma patients.

The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma

Yen-Hsiang Huang,Kuo-Hsuan Hsu,Jeng-Sen Tseng,Kun-Chieh Chen,Chia-Hung Hsu,Kang-Yi Su,Jeremy J. W. Chen,Huei-Wen Chen,Sung-Liang Yu,Tsung-Ying Yang,Gee-Chen Chang 대한암학회 2018 Cancer Research and Treatment Vol.50 No.4

Purpose The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)mutant lung adenocarcinoma patients with acquired resistance after firstline EGFRtyrosine kinase inhibitor (TKI) treatment. Materials and Methods We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFRmutation status. Results A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression- free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). Conclusion PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

Evaluation of Ecological Function of Mangrove Soil on Absorbing Heavy Metals: A Case Study from the Dongzhaigang Mangrove in China

Kun Xin,Xing Huang,Zhili Chen 한국생태학회 2010 Journal of Ecology and Environment Vol.33 No.1

Mangroves are special plant communities that live along intertidal zones in tropical and subtropical areas. They are regarded as one of the most important types of natural ecosystem in the world because of the many ecosystem functions that they perform, of which water purification is the most complex. Mangrove ecosystems are conducive to the deposition and retention of heavy metals. So it is important to understand the impact of heavy metals on mangrove ecosystems, and especially on soil subsystems. We examined the levels of heavy metals in the soil of mangroves in the Dongzhaigang Mangrove National Nature Reserve. Dongzhaigang, the first mangrove nature reserve established in China, is located south of Haikou in Hainan Island and encompasses 33.37 ㎢, of which mangroves comprise 20.56km2. To assess the impact of human activities, we collected a large number of soil samples in four sampling areas (the protection station, the harbor, a tour area, and Yeboluo island) in the study area. We measured the concentrations of Cu,Pb, Zn and Cd in the soil samples using the spectra of polyatomic molecules. The average concentrations of Cu, Pb, Zn and Cd were 5.04 μg/g, 10.36 μg/g, 20.06 μg/g and 0.06 μg/g, respectively, and the heavy metal concentrations were lowest in the protected area, highest in the harbor, and intermediate in Yeboluo Island and the tour area. The heavy metal concentrations in the soil collected from different sample plots are related not only to the physical and chemical properties of the soil, but also to the heavy metal emitted by nearby pollution sources. Our analysis indicates that tourist boats are the main pollution sources in the study area.

Decreased Expression of LKB1 Correlates with Poor Prognosis in Hepatocellular Carcinoma Patients Undergoing Hepatectomy

Huang, Yue-Han,Chen, Zhen-Kun,Huang, Ka-Te,Li, Peng,He, Bin,Guo, Xu,Zhong, Jun-Qiao,Zhang, Qi-Yu,Shi, Hong-Qi,Song, Qi-Tong,Yu, Zheng-Ping,Shan, Yun-Feng Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Aim: To study any correlation of LKB1 expression with prognosis in hepatocellular carcinoma (HCC) cases. Methods: A total of 70 HCC patients and 20 primary intrahepatic stone patients in the first affiliated hospital of Wenzhou Medical College were enrolled in this study. LKB1 expression was detected by immunohistochemistry. Patients were followed-up and prognostic factors were evaluated. Result: LKB1 expression was decreased in the HCC samples. Loss of LKB1 expression in HCC was significantly related to histologic grade (P=0.010), vascular invasion (P=0.025) and TMN stage (P=0.011). Patients showing negative LKB1 expression had a significantly shorter disease-free and overall survival than those with positive expression (P = 0.001, P=0.000, respectively). Multivariate Cox regression analysis indicated that LKB1 expression level was an independent factor of survival (P = 0.033). Conclusion: HCC patients with decreased expression LKB1 have a poor prognosis. The loss of LKB1 expression is correlated with a lower survival rate.

Sensorless Control of Wound Rotor Synchronous Machines Based on High-frequency Signal Injection into the Stator Windings

Chen, Zhiguo,Deng, Xianming,Huang, Kun,Zhen, Wenhuan,Wang, Lei The Korean Institute of Power Electronics 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.4

This paper proposes a sensorless control approach for Wound Rotor Synchronous Machines (WRSMs) based on a high frequency voltage signal injection into the stator side U phase and VW line, respectively. Considering the machine itself as a rotor position sensor, the rotor position observer is established according to the principles of the rotary transformer. A demodulation method for the high frequency signal inducted in the rotor is proposed as well. Simulation and experimental results show that the proposed sensorless control approach has high performance and good practicability.

Sensorless Control of Wound Rotor Synchronous Machines Based on High-frequency Signal Injection into the Stator Windings

Zhiguo Chen,Xianming Deng,Kun Huang,Wenhuan Zhen,Lei Wang 전력전자학회 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.4

This paper proposes a sensorless control approach for Wound Rotor Synchronous Machines (WRSMs) based on a high frequency voltage signal injection into the stator side U phase and VW line, respectively. Considering the machine itself as a rotor position sensor, the rotor position observer is established according to the principles of the rotary transformer. A demodulation method for the high frequency signal inducted in the rotor is proposed as well. Simulation and experimental results show that the proposed sensorless control approach has high performance and good practicability.

Endophytic fungi harbored in Panax notoginseng: diversity and potential as biological control agents against host plant pathogens of root-rot disease

You-Kun Zheng,Cui-Ping Miao,Hua-Hong Chen,Fang-Fang Huang,Yu-Mei Xia,You-Wei Chen,Li-Xing Zhao 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: Endophytic fungi play an important role in balancing the ecosystem and boosting host growth. In the present study, we investigated the endophytic fungal diversity of healthy Panax notoginseng and evaluated its potential antimicrobial activity against five major phytopathogens causing rootrot of P. notoginseng. Methods: A culture-dependent technique, combining morphological and molecular methods, was used to analyze endophytic fungal diversity. A double-layer agar technique was used to challenge the phytopathogens of P. notoginseng. Results: A total of 89 fungi were obtained from the roots, stems, leaves, and seeds of P. notoginseng, and 41 isolates representing different morphotypes were selected for taxonomic characterization. The fungal isolates belonged to Ascomycota (96.6%) and Zygomycota (3.4%). All isolates were classified to 23 genera and an unknown taxon belonging to Sordariomycetes. The number of isolates obtained from different tissues ranged from 12 to 42 for leaves and roots, respectively. The selected endophytic fungal isolates were challenged by the root-rot pathogens Alternaria panax, Fusarium oxysporum, Fusarium solani, Phoma herbarum, and Mycocentrospora acerina. Twenty-six of the 41 isolates (63.4%) exhibited activity against at least one of the pathogens tested. Conclusion: Our results suggested that P. notoginseng harbors diversified endophytic fungi that would provide a basis for the identification of new bioactive compounds, and for effective biocontrol of notoginseng root rot.