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https://www.readbyqxmd.com/read/28431037/gestational-diabetes-alters-functions-in-offspring-s-umbilical-cord-cells-with-implications-for-cardiovascular-health
#1
Ajith Isaac Amrithraj, Anjaneyulu Kodali, Linh Nguyen, Adrian Kee Keong Teo, Cheng Wei Chang, Neerja Karnani, Kai Lyn Ng, Peter D Gluckman, Yap Seng Chong, Walter Stünkel
As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. We have assessed primary umbilical cord derived cells such as human umbilical vein endothelial cells (HUVECs) and Wharton's jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and non-GDM mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, and the ability to support blood vessel growth...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#2
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421904/effects-of-1alpha-25-dihydroxyvitamin-d3-on-programmed-cell-death-of-ishikawa-endometrial-cancer-cells-through-ezrin-phosphorylation
#3
Tae-Hee Kim, Junsik Park, Jeong-Sang Lee, Hae-Hyeog Lee
This study investigated the effects of 1α, 25-dihydroxyvitamin D3-induced cell death and its underlying molecular mechanisms in Ishikawa endometrial carcinoma cells. The effects of 1α, 25-dihydroxyvitamin D3 on Ishikawa cells were examined by 3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyl-tetrazolium bromide, thiazolyl blue (MTT) assay. 1α, 25-dihydroxyvitamin D3 was shown to induce programmed cell death in Ishikawa endometrial carcinoma cells by activation of caspase-3 and caspase-9, along with elevation of Bcl-2 and Bcl-xL...
May 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28418907/bh3-mimetics-and-bet-inhibitors-elicit-enhanced-lethality-in-malignant-glioma
#4
Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Marc-Eric Halatsch, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D Siegelin
Drug combination therapies remain pivotal for the treatment of heterogeneous malignancies, such as glioblastomas. Here, we show a novel lethal interaction between Bcl-xL and c-myc inhibition accomplished by bromodomain protein inhibitors. Established, patient-derived xenograft and stem cell-like glioma cells were treated with the novel bromodomain protein inhibitors, JQ1 and OTX015, along with BH3-mimetics, ABT263 or Obatoclax. Synergy was assessed by calculation of CI values. Small interfering RNAs (siRNAs) were used for gene silencing and mechanistic studies...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416958/keratinization-of-lung-squamous-cell-carcinoma-is-associated-with-poor-clinical-outcome
#5
Hye Jung Park, Yoon-Jin Cha, Seong Han Kim, Arum Kim, Eun Young Kim, Yoon Soo Chang
BACKGROUND: Although the World Health Organization (WHO) classification of lung squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for lung SCC subsets remain unclear. We investigated whether the morphologic characteristics of lung SCC, including keratinization, were associated with clinical parameters and clinical outcome of patients. METHODS: A total of 81 patients who underwent curative surgical resection of diagnosed lung SCC, were enrolled in this study...
April 2017: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28416455/protection-from-cr-vi-induced-malignant-cell-transformation-and-tumorigenesis-of-cr-vi-transformed-cells-by-luteolin-through-nrf2-signaling
#6
Young-Ok Son, Poyil Pratheeshkumar, Yuting Wang, Donghern Kim, Zhuo Zhang, Xianglin Shi
Cr(VI) is a well known environmental carcinogen, but its mechanism of action and the measures required to mitigate its effects remain to be investigated. Our previous studies showed that exposure of human bronchial epithelial (BEAS-2B) cells to Cr(VI) caused malignant transformation, that these transformed cells progressed through tumorigenesis, and that luteolin, a natural compound, inhibited both of these processes. The present study investigates the underlying mechanisms by which luteolin protects cells against Cr(VI)-induced transformation and tumorigenesis...
April 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28415735/salicylate-%C3%A2-phenanthroline-copper-ii-complex-induces-apoptosis-in-triple-negative-breast-cancer-cells
#7
Limei Fan, Muyou Tian, Yunyi Liu, Ying Deng, Zhengkai Liao, Jinhua Xu
In this study, we investigated anti-tumor activity and associated molecular mechanism of action of Salicylate ●Phenanthroline Copper (II) Complex in triple-negative breast cancer. Salicylate ●Phenanthroline Copper (II) Complex inhibited the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20) and induced apoptosis in a concentration-dependent manner. The effect was more profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines. Western blot showed that the expression of the apoptosis-related protein Bcl-2, Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with Salicylate ●Phenanthroline Copper (II) Complex...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415611/mrna-in-exosomas-as-a-liquid-biopsy-in-non-hodgkin-lymphoma-a-multicentric-study-by-the-spanish-lymphoma-oncology-group
#8
Mariano Provencio, Marta Rodríguez, Blanca Cantos, Pilar Sabín, Cristina Quero, Francisco R García-Arroyo, Antonio Rueda, Constanza Maximiano, Delvys Rodríguez-Abreu, Antonio Sánchez, Javier Silva, Vanesa García
PURPOSE: To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-κβ, PTEN and AKT) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. PATIENTS AND METHODS: Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. RESULTS: In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413517/isoflurane-anesthesia-induces-liver-injury-by-regulating-the-expression-of-insulin-like-growth-factor-1
#9
Yingxian Zhu, Xiaoyu Xiao, Guowei Li, Juyuan Bu, Wenying Zhou, Shaopeng Zhou
It has been suggested that isoflurane may cause perioperative liver injury. However, the mechanism of its action remains unknown. The purpose of the present study was to determine this possible mechanism. Sprague-Dawley rats were randomly assigned into one of three groups (all n=12): Control group (exposed to mock anesthesia), isoflurane group (exposed to 2% isoflurane for 90 min), and isoflurane + insulin-like growth factor 1 (IGF-1) group (exposed to 2% isoflurane for 90 min and then treated with IGF-1). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the levels of expression of IGF-1 and its receptor IGF-R...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28410209/mir-106b-inhibitors-sensitize-trail-induced-apoptosis-in-hepatocellular-carcinoma-through-increase-of-death-receptor-4
#10
Changlong Xu, Liang Shi, Weilai Chen, Peipei Fang, Jie Li, Lingxiang Jin, Zhenzhen Pan, Chenwei Pan
TNF-related apoptosis-inducing ligand (TRAIL), which is a member of the TNF superfamily, can induce tumor cell apoptosis. However, multiple types of tumor, including hepatocellular carcinoma, show tolerance to TRAIL. Previous studies have demonstrated that tumor cells usually change their expression profile of microRNA (miRNA) to obtain the ability of tolerance to drugs. However, whether such change of miRNA on TRAIL sensitivity is seen in hepatocellular carcinoma still needs to be explored. In this study, we observed overexpression of miR-106b in both HCC patients' tumor tissues and cell lines...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408883/alisol-a-24-acetate-and-alisol-b-23-acetate-induced-autophagy-mediates-apoptosis-and-nephrotoxicity-in-human-renal-proximal-tubular-cells
#11
Chunfei Wang, Liang Feng, Liang Ma, Haifeng Chen, Xiaobin Tan, Xuefeng Hou, Jie Song, Li Cui, Dan Liu, Juan Chen, Nan Yang, Jing Wang, Ying Liu, Bingjie Zhao, Gang Wang, Yuanli Zhou, Xiaobin Jia
Two natural compounds alisol A 24-acetate (24A) and alisol B 23-acetate (23B) are abundant in Rhizoma alismatis. In the present study, we evaluated the induction of 24A and 23B on apoptosis and possible nephrotoxicity of human renal proximal tubular (HK-2) cells by activating autophagy and also explored its regulation on PI3K/Akt/mTOR signaling pathway. Presently, Clusterin, Kim-1, and TFF-3 were considered to be new bioindicators of nephrotoxicity. Interestingly, the protein expression and mRNA levels of Clusterin, Kim-1 and TFF-3 could be significantly increased by 23B and 24A in vivo and in vitro...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28404874/identification-of-jl1037-as-a-novel-specific-reversible-lysine-specific-demethylase-1-inhibitor-that-induce-apoptosis-and-autophagy-of-aml-cells
#12
Shuang Liu, Wenting Lu, Shouyun Li, Saisai Li, Jia Liu, Yuanyuan Xing, Shuzu Zhang, Joe Zhongxiang Zhou, Haiyan Xing, Yingxi Xu, Qing Rao, Chengjun Deng, Min Wang, Jianxiang Wang
Lysine-specific demethylase 1 (LSD1) has been recognized as a potential therapeutic target for acute myeloid leukemia (AML). Herein, we identified a novel LSD1 inhibitor, JL1037, via Computer Aided Drug Design technology. JL1037 is a potent, selective and reversible LSD1 inhibitor with IC50s of 0.1 μM and >1.5 μM for LSD1 and monoamine oxidases A/B (MAO-A/B), respectively. Treatment of THP-1 and Kasumi-1 cell lines with JL1037 resulted in dose dependent accumulation of H3K4me1 and H3K4me2, the major substrates of LSD1, as well as inhibition of cell proliferation, blockade of cell cycle and induction of apoptosis...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402264/fhl2-interacts-with-iaspp-and-impacts-the-biological-functions-of-leukemia-cells
#13
Wenting Lu, Tengteng Yu, Shuang Liu, Saisai Li, Shouyun Li, Jia Liu, Yingxi Xu, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Jianxiang Wang, Min Wang
iASPP is an inhibitory member of apoptosis-stimulating proteins of p53 (ASPP) family, which inhibits p53-dependent apoptosis. iASPP was highly expressed in acute leukemia, inhibited leukemia cells apoptosis and promoted leukemogenesis. In order to clarify its mechanism, a yeast two-hybrid screen was performed and FHL2 was identified for the first time as one of the binding proteins of iASPP. FHL2 was highly expressed in K562 and Kasumi-1 cells. FHL2 and iASPP interacted with each other and co-localized in both nucleus and cytoplasm...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401933/bcl-xl-mediates-ripk3-dependent-necrosis-in-m-tuberculosis-infected-macrophages
#14
X Zhao, N Khan, H Gan, F Tzelepis, T Nishimura, S-Y Park, M Divangahi, H G Remold
Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28399853/the-anti-cancer-effects-of-tualang-honey-in-modulating-breast-carcinogenesis-an-experimental-animal-study
#15
Sarfraz Ahmed, Nor Hayati Othman
BACKGROUND: Honey has been shown to have anti-cancer effects, but the mechanism behind these effects is not fully understood. We investigated the role of Malaysian jungle Tualang honey (TH) in modulating the hematological parameters, estrogen, estrogen receptors (ER1) and pro and anti-apoptotic proteins expression in induced breast cancer in rats. METHODS: Fifty nulliparous female Sprague-Dawley rats were used and grouped as follows: Group 0 (healthy normal rats control), Group 1 (negative control; untreated rats), Groups 2, 3 and 4 received daily doses of 0...
April 11, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28395806/generation-of-human-ipscs-from-an-essential-thrombocythemia-patient-carrying-a-v501l-mutation-in-the-mpl-gene
#16
Senquan Liu, Zhaohui Ye, Yongxing Gao, Chaoxia He, Donna W Williams, Alison Moliterno, Jerry Spivak, He Huang, Linzhao Cheng
Activating point mutations in the MPL gene encoding the thrombopoietin receptor are found in 3%-10% of essential thrombocythemia (ET) and myelofibrosis patients. Here, we report the derivation of induced pluripotent stem cells (iPSCs) from an ET patient with a heterozygous MPL V501L mutation. Peripheral blood CD34(+) progenitor cells were reprogrammed by transient plasmid expression of OCT4, SOX2, KLF4, c-MYC plus BCL2L1 (BCL-xL) genes. The derived line M494 carries a MPL V501L mutation, displays typical iPSC morphology and characteristics, are pluripotent and karyotypically normal...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28394923/effects-and-underlying-mechanisms-of-irisin-on-the-proliferation-and-apoptosis-of-pancreatic-%C3%AE-cells
#17
Shiwei Liu, Fang Du, Xin Li, Mingming Wang, Ruixue Duan, Jiaxin Zhang, Yaru Wu, Qi Zhang
Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28386742/4-parvifuran-inhibits-metastatic-and-invasive-actions-through-the-jak2-stat3-pathway-in-osteosarcoma-cells
#18
Hyung-Mun Yun, Kyung-Ran Park, Tran Hong Quang, Hyuncheol Oh, Jin Tae Hong, Youn-Chul Kim, Eun-Cheol Kim
This study was performed to examine the anticancer and anti-metastatic effects of 4-parvifuran (PVN), a novel flavonoid isolated from the heartwood of Dalbergia odorifera, and to study its underlying signaling pathway in human osteosarcoma cells. In the present study, PVN was found to inhibit cell proliferation in a concentration- and time-dependent manner in the human osteosarcoma cell lines studied (MG-63 and U-2 OS) and induce apoptosis, as evidenced by Annexin V(+) and TUNEL(+) cells. Cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3 were up-regulated while anti-apoptotic proteins including Bcl-2, Bcl-xL, and survivin were down-regulated after treatment with PVN...
April 6, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28386457/clearing-the-outer-mitochondrial-membrane-from-harmful-proteins-via-lipid-droplets
#19
Johannes Bischof, Manuel Salzmann, Maria Karolin Streubel, Jiri Hasek, Florian Geltinger, Jutta Duschl, Nikolaus Bresgen, Peter Briza, Danusa Haskova, Renata Lejskova, Mentor Sopjani, Klaus Richter, Mark Rinnerthaler
In recent years it turned out that there is not only extensive communication between the nucleus and mitochondria but also between mitochondria and lipid droplets (LDs) as well. We were able to demonstrate that a number of proteins shuttle between LDs and mitochondria and it depends on the metabolic state of the cell on which organelle these proteins are predominantly localized. Responsible for the localization of the particular proteins is a protein domain consisting of two α-helices, which we termed V-domain according to the predicted structure...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28386317/alisertib-induces-g2-m-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-mediated-pathways-in-human-glioblastoma-cells
#20
Zheng Liu, Feng Wang, Zhi-Wei Zhou, He-Chun Xia, Xin-Yu Wang, Yin-Xue Yang, Zhi-Xu He, Tao Sun, Shu-Feng Zhou
Glioblastoma (GBM) is the most common brain tumor with poor response to current therapeutics. Alisertib (ALS), a second-generation selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects on solid tumors in animal studies. This study aimed to investigate the killing effect of ALS on GBM cell line DAOY and the possible underlying mechanisms using both bioinformatic and cell-based approaches. Our molecular docking showed that ALS preferentially bound AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking...
2017: American Journal of Translational Research
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