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PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease 下载免费PDF全文
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Yu-Tzu Chan Alan C.-Y. Lai Ruey-Jen Lin Ya-Hui Wang Yi-Ting Wang Wen-Wei Chang Hsin-Yi Wu Yu-Ju Lin Wen-Ying Chang Jen-Chine Wu Jyh-Cherng Yu Yu-Ju Chen Alice L. Yu 《International journal of cancer. Journal international du cancer》2020,146(6):1674-1685
G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER−/PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs. 相似文献
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Hsin-Yi Tseng Jan Dreyer Abdullah Al Emran Dilini Gunatilake Mehdi Pirozyan Carleen Cullinane Ken Dutton-Regester Helen Rizos Nicholas K. Hayward Grant McArthur Peter Hersey Jessamy Tiffen Stuart Gallagher 《International journal of cancer. Journal international du cancer》2020,147(8):2176-2189
The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anticancer therapeutics targeting the MCL1 anti-apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra-terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti-apoptotic targets regulated by NF-kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro-apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I-BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3-only protein, BIM, and downregulated anti-apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell lines. ABT-199 or ABT-263 inhibitors against BCL2 or BCL2 and BCLXL, respectively, induced further cell death when combined with S63845 and I-BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance. 相似文献
6.
Ming-Yeh Yang Ching-Yuan Huang Tina H.T. Chiu Kai-Chih Chang Ming-Nan Lin Liang-Yü Chen Anren Hu 《Yao wu shi pin fen xi = Journal of food and drug analysis.》2019,27(2):494-501
Vitamin D is responsible for multiple metabolic functions in humans. Rickets are the most common disease caused by vitamin D deficiency. It is caused by poor calcium intake resulting in poor serum-ionized calcium. The purpose of this study is to develop a rapid, sensitive, and feasible method to determine the 25-hydroxy-vitamin D3 (25(OH)D3) levels in blood samples for clinical assessment. In this study, gas chromatography coupled mass spectrometry with trimethylsilyl derivatization (TMS-GC-MS) is the most suitable protocol for quantitative analyses of 25(OH)D3. Performance of method was evaluated and compared with liquid chromatography and immunoassay. Method validation has been carried out with plasma specimens. The limit of quantitation of TMS-GC-MS method is 1.5 ppb with good linear correlation. Furthermore, the dietary intake and nutritional status of vegetarian and non-vegetarians in Taiwan were assessed by our validated method. As a result, this vitamin D nutrition survey demonstrates that most Taiwanese people have insufficient vitamin D. Due to dietary habits; the male vegans may have the highest risk of vitamin D deficiency. 相似文献
7.
Meng-Luen Lee Lon-Yen Tsao Wun-Tsong Chaou Albert D Yang Kun-Tu Yeh Jou-Kou Wang Mei-Hwan Wu Hung-Chi Lue Ing-Sh Chiu Chung-I Chang 《Pediatric pulmonology》2002,33(1):1-11
We propose a haphazard branching theory to support the concept of bronchopulmonary malinosculations, and we apply this theory to classify congenital bronchopulmonary vascular malformation (BPVM) based on the anatomical results we have found. Between January 1990 and December 1997, a total of 22 pediatric patients (10 male and 12 female), aged 2 days to 14 years (median, 19.6 months), with congenital BPVM were enrolled in this retrospective study. Study modalities include the clinical features and plain chest films (n = 22) plus at least two of the following: echocardiography (n = 13), barium esophagraphy (n = 2), bronchoscopy (n = 4), contrast bronchography (n = 8), high-resolution direct coronal CT (n = 1) and electron beam or ultrafast CT (n = 1) of the chest, MRI (n = 10), MRA (n = 1), contrast cineangiocardiography (n = 9), surgery (n = 11), or autopsy (n = 2). The salient clinical features were recurrent lung infections in 14 patients, acute respiratory distress in 13, associated cardiovascular malformations in 8, dextroversion in 7, congestive heart failure in 7, dextrocardia in 4, and complex congenital heart diseases in 4. There were abnormal openings (malinosculations) of the pulmonary airway in 20 patients: to an artery in 12, to a vein in 8, and to the lung parenchyma in 9. These 22 patients with congenital BPVM can be classified into bronchial malinosculation (10 cases), arterial malinosculation (2 cases), and bronchoarterial malinosculation (10 cases). Congenital BPVM can be classified in terms of bronchopulmonary malinosculation based upon a haphazard branching theory, in which abnormal communications between two independent systems (primitive foregut system and aortic-pulmonary arch system) occurred coincidentally rather than causally. 相似文献
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Schefflera heptaphylla (L.) Frodin is a medicinal herb widely used as a main ingredient of the popular health tea formulation against infections in Southern China. Twenty-seven volatile compounds were identified by GC-MS analysis from the essential oil obtained from the leaves of S. heptaphylla, and 17 of them belonged to monoterpenes or sesquiterpenes. The main volatile constituent in S. heptaphylla was found to be a monoterpene, beta-pinene, comprising about 22% of the total volatile components. The essential oil showed significant antiproliferative activity against three cancer cell lines, MCF-7, A375 and HepG2 cells, with IC50 values of 7.3 microg/mL, 7.5 microg/mL and 6.9 microg/mL, respectively. The result of the cytotoxicity assay indicates that (-)-beta-pinene and (+)-beta-pinene (commercially available from Sigma) also possessed antiproliferative activity against the cancer cells MCF-7, A375 and HepG2 with IC50 values ranging from 147.1 to 264.7 microm. 相似文献
9.
Fu-Wei Wang Yu-Wen Chiu Ming-Shium Tu Ming-Yueh Chou Chao-Ling Wang Hung-Yi Chuang 《International archives of occupational and environmental health》2009,82(7):819-825
Purpose There has been increasing interest in the occupational health of workers in small enterprises, especially in developing countries.
This study examines the association between psychosocial job characteristics and fatigue, and attempts to identify risk factors
for fatigue among workers of small enterprises in southern Taiwan.
Methods A structured questionnaire was administered to workers receiving regular health examinations between August 2005 and January
2006. The questionnaire collected demographic information and data on working conditions, personal health status and life
styles. It also collected information on psychosocial job characteristics, fatigue and psychological distress using three
instruments.
Results A total of 647 workers with mean age of 43.7 were completed. Probable fatigue was found in 34.6% of the sample. Fatigue was
found by multiple logistic regressions to be associated with the lack of exercise, working in shifts, depression score and
lack of social support at workplace.
Conclusions This study found associations between life style, psychosocial job characteristics and fatigue. Because the high prevalence
of probable fatigue was found in such small enterprises, the authors suggest that a short interview with some quick questionnaires
in health checkup for these small enterprise workers are helpful to early detect psychosocial and fatigue problems. 相似文献
10.
Wan-Chen Tsai Wen-Ta Chiu Hung-Yi Chiou Cheuk-Sing Choy Ching-Chang Hung Shin-Han Tsai 《Journal of clinical neuroscience》2004,11(2):126-129
Background. This study is intended to determine the causes of pediatric traumatic brain injuries (PTBI) in children aged 14 years or less, and to identify various types of craniocerebral damage resulting from different mechanisms of injury.Methods. From July 1, 1993 to June 30, 2001, a survey on PTBI was conducted in Taiwan. The data of patients used in this study were collected from 56 major hospitals among the age group of 0-14 years. The items in the traumatic brain injury survey included sex, age, causes of injuries, severity, and the eventual outcome.Results. A total of 5349 cases were identified. The male-to-female ratio was 1.69: 1. The incidence rate was higher in the age groups of 4-9 years and 10-14 years. The main cause of PTBI was traffic injury, which accounted for 2537 of the cases (47.3%), followed by falls, 2160 (40.3%). Of all traffic injuries, motorcycle-related injury had the highest incidence, followed by the pedestrian and bicycle-related injury. This study also showed that 83.2% of the patients had mild injury, 9.8% had moderate injury, and 7.0%, severe injury.Conclusions. The results of this study suggest that it is important to decrease all the risk factors in the environment of homes and public areas as much as possible. Helmet wearing and the development of public transportation are essential for the prevention of head injury. 相似文献