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https://www.readbyqxmd.com/read/29345855/increased-estradiol-in-hepatitis-e-virus-infected-pregnant-women-promote-viral-replication
#1
Chenchen Yang, Wenhai Yu, Yanhong Bi, Feiyan Long, Yunlong Li, Daqiao Wei, Xianhui Hao, Jianwen Situ, Yongqin Zhao, Fen Huang
Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high mortality (> 25%) in pregnant women. HEV replication is aggressively escalated in pregnant women, especially in the third trimester of pregnancy. Estrogen plays an important role in pregnancy. However, the pathogenesis of HEV in pregnant women or immunosuppressive pregnant women (such as HIV-infected, or organ-transplanted pregnant women) remains unclear. We investigated the role of estradiol in HEV infection in a cell culture system...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345747/recurrent-iga-nephropathy-after-renal-transplantation-and-steroid-withdrawal
#2
Maria Cristina di Vico, Maria Messina, Fabrizio Fop, Antonella Barreca, Giuseppe Paolo Segoloni, Luigi Biancone
Immunoglobulin A Nephropathy (IgAN), is the most common primary glomerulonephritis; the reported recurrence rate of IgAN after renal transplantation is as high as 13-50%. The impact of immunosuppressive therapy and steroid withdrawal on the risk of recurrence of IgAN is still under debate. We performed a retrospective single center study, selecting 123 kidney transplants (rtx) in 120 patients, between January 1995 and December 2012, with IgAN on the native kidney. In 51/123 at least one post transplantation biopsy for clinical indication was performed; in 28/51 transplants IgAN recurrence (IgANr) was demonstrated...
January 18, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29345570/the-role-of-ampk-mtor-modulators-in-therapy-of-acute-myeloid-leukemia
#3
Dora Visnjic, Vilma Dembitz, Hrvoje Lalic
Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic acid represents the most successful pharmacological therapy of acute myeloid leukemia (AML). Numerous studies demonstrate that drugs that inhibit mechanistic target of rapamycin (mTOR) and activate AMP-kinase (AMPK) have beneficial effects in promoting differentiation and blocking proliferation of AML. Most of these drugs are already in use for other purposes; rapalogs as immunosuppressants, biguanides as oral antidiabetics, and 5-amino-4-imidazolecarboxamide ribonucleoside (AICAr, acadesine) as an exercise mimetic...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345360/mtor-a-double-edged-sword-for-diabetes
#4
REVIEW
Yali Tuo, Ming Xiang
Diabetes is both a metabolic and an immune disorder. One intriguing link between the two is the serine-threonine protein kinase mammalian target of rapamycin (mTOR). As a component of the PI3K/Akt pathway and other cellular signals, mTOR is a key regulator of fuel metabolism and function of both pancreatic islet β cells and immune cells. Consequently, it seems that mTOR has both anti- and prodiabetic effects. On the one hand, activation of mTOR in β cells can increase their growth and proliferation, opposing impairments of insulin secretion in diabetes...
January 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345357/the-prognostic-value-of-pi3k-mutational-status-in-breast-cancer-a-meta-analysis
#5
N Sobhani, G Roviello, S P Corona, M Scaltriti, A Ianza, M Bortul, F Zanconati, D Generali
Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20-40% of BC. We performed a meta-analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor and predictor of response to anti-cancer treatments...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29345288/downregulation-of-mir%C3%A2-205-is-associated-with-glioblastoma-cell-migration-invasion-and-the-epithelial-mesenchymal-transition-by-targeting-zeb1-via-the-akt-mtor-signaling-pathway
#6
Wei Chen, Kuan-Kei Kong, Xin-Ke Xu, Cheng Chen, Hui Li, Fang-Yu Wang, Xiao-Fang Peng, Zhan Zhang, Ping Li, Jun-Liang Li, Fang-Cheng Li
Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of recent advancements in surgical techniques, chemotherapy, and radiation therapy, patients with GBM often face a dire prognosis. MicroRNAs have been shown to modulate the aggressiveness of various cancers, and have emerged as possible therapeutic agents for the management of GBM. miR‑205 is dysregulated in glioma and act as a prognostic indicator. However, the role of miR‑205 in the development of GBM has not been elucidated...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345254/the-mtor-inhibitor-azd8055-overcomes-tamoxifen-resistance-in-breast-cancer-cells-by-down-regulating-hspb8
#7
Jia-Jie Shi, Si-Meng Chen, Chen-Liang Guo, Yi-Xue Li, Jian Ding, Ling-Hua Meng
Tamoxifen, an important endocrine therapeutic agent, is widely used for the treatment of estrogen receptor positive (ER+) breast cancer. However, de novo or acquired resistance prevents patients from benefitting from endocrine approaches and necessitates alternative treatments. In this study, we report that small heat protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen resistance. HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen (MCF-7/R) compared to parent cells. Moreover, high expression of HSPB8 associates with poor prognosis in ER+ breast cancer patients but not in patients without classification...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29344971/clear-cell-carcinomas-of-the-ovary-and-kidney-clarity-through-genomics
#8
REVIEW
Jennifer X Ji, Yi Kan Wang, Dawn R Cochrane, David G Huntsman
Clear cell ovarian carcinoma (CCOC) and clear cell renal cell carcinoma (ccRCC) both feature clear cytoplasm due to the accumulation of cytoplasmic glycogen. Genomic studies have demonstrated several mutational similarities between these two diseases including frequent alterations in the chromatin remodeling SWI/SNF and cellular proliferation PI3K/mTOR pathways, as well as a shared hypoxia-like mRNA expression signature. Although many targeted treatment options have been approved for advance stage ccRCC, CCOC patients are still treated with conventional platinum and taxane chemotherapy, to which they are resistant...
January 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29344654/tunicamycin-inhibits-colon-carcinoma-growth-and-aggressiveness-via-modulation-of-the-erk-jnk-mediated-akt-mtor-signaling-pathway
#9
Shuping You, Weihong Li, Yun Guan
Epidemiology and evidence have demonstrated that colon carcinoma is one of the most common gastrointestinal tumors in the clinic. Reports have suggested that Tunicamycin significantly inhibits aggressiveness of colon carcinoma cells by promotion of apoptosis. In the present study, the inhibitory effect of tunicamycin on colon cancer cells and the potential underlying molecular mechanism was investigated. Western blotting, immunohistochemistry, apoptotic assays and immunofluorescence were used to analyze the therapeutic effects of tunicamycin on apoptosis, growth, aggressiveness and cell cycle of colon tumor cells, by downregulation of fibronectin, vimentin and E‑cadherin expression levels...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344647/autophagy-regulates-the-degeneration-of-the-auditory-cortex-through-the-ampk-mtor-ulk1-signaling-pathway
#10
Jie Yuan, Xueyan Zhao, Yujuan Hu, Haiying Sun, Guoqing Gong, Xiang Huang, Xubo Chen, Mingyu Xia, Chen Sun, Qilin Huang, Yu Sun, Wen Kong, Weijia Kong
Presbycusis is the most common sensory impairment associated with aging; however, the underlying molecular mechanism remains unclear. Autophagy has been demonstrated to serve a key role in diverse diseases; however, no studies have examined its function in central presbycusis. The aim of the present study was to investigate the changes of autophagy in the physiological processes of the auditory cortex and its role in the degeneration of the auditory cortex, as well as the related mechanisms using naturally aging rats and a D‑galactose (D‑gal)‑induced mimetic rat model of aging...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344641/inhibition-of-rptor-overcomes-resistance-to-egfr-inhibition-in-triple-negative-breast-cancer-cells
#11
Kyu Sic You, Yong Weon Yi, Sahng-June Kwak, Yeon-Sun Seong
Triple-negative breast cancer (TNBC) cells frequently exhibit activated growth factor signaling and resistance to inhibitors for epidermal growth factor receptor (EGFR), despite the overexpression of EGFR protein, and this is associated with a malignant behavior and a poor prognosis. In this study, to elucidate the underlying mechanisms of resistance to EGFR inhibitor and identify inhibitors that exert a synergistic effect with EGFR inhibition, we examined the inhibitory effects of selected protein kinase inhibitors (PKIs) in combination with gefitinib on the viability of a mesenchymal stem-like (MSL) subtype TNBC cell line...
January 15, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344639/therapeutic-potential-of-a-dual-mtorc1-2-inhibitor-for-the-prevention-of-posterior-capsule-opacification-an-in-vitro-study
#12
Hao Feng, Zhibo Yang, Xue Bai, Meirong Yang, Yuan Fang, Xiaonan Zhang, Qiqiang Guo, Hong Ning
Mammalian target of rapamycin (mTOR) serves a central role in regulating cell growth and survival, and has been demonstrated to be involved in the pathological progression of posterior capsule opacification (PCO). In the present study, the potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the suppression of the growth of human lens epithelial cells (HLECs) was investigated. Using a Cell Counting Kit‑8 and a wound healing assay, it was demonstrated that PP242 inhibited the proliferation and migration of HLECs...
January 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344415/rhizoma-coptidis-and-berberine-as-a-natural-drug-to-combat-aging-and-aging-related-diseases-via-anti-oxidation-and-ampk-activation
#13
REVIEW
Zhifang Xu, Wei Feng, Qian Shen, Nannan Yu, Kun Yu, Shenjun Wang, Zhigang Chen, Seiji Shioda, Yi Guo
Aging is the greatest risk factor for human diseases, as it results in cellular growth arrest, impaired tissue function and metabolism, ultimately impacting life span. Two different mechanisms are thought to be primary causes of aging. One is cumulative DNA damage induced by a perpetuating cycle of oxidative stress; the other is nutrient-sensing adenosine monophosphate-activated protein kinase (AMPK) and rapamycin (mTOR)/ ribosomal protein S6 (rpS6) pathways. As the main bioactive component of natural Chinese medicine rhizoma coptidis (RC), berberine has recently been reported to expand life span in Drosophila melanogaster, and attenuate premature cellular senescence...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29344249/estradiol-suppresses-phosphorylation-of-er%C3%AE-serine-167-through-upregulation-of-pp2a-in-breast-cancer-cells
#14
Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Nobuhiro Harada, Toshiaki Utsumi
Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344236/alterations-in-expression-levels-of-genes-in-p53-related-pathways-determined-using-rna-seq-analysis-in-patients-with-breast-cancer-following-cik-therapy
#15
Zuowei Hu, Xiaoye Zhang, Hang Yang, Shuanglai Qin, Yaqi Liu, Wei Xiong, Bing Yuan, Liping Li, Weiqi Yao, Dongcheng Wu
The present study aimed at investigating the underlying molecular mechanisms for patients following cytokine-induced killer (CIK) therapy, particularly involving the alterations in p53-associated signaling pathways, to elucidate whether CIK therapy serves a function in cancer treatment. Samples of blood were collected from patients with breast cancer prior to and following CIK therapy. Two group samples were used for RNA sequencing (RNA-Seq) to determine the alterations in gene expression levels following CIK therapy and one for the quantitative polymerase chain reaction (qPCR), to analyze the reliability of RNA-Seq results...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344181/l-type-amino-acid-transporter-1-expression-is-upregulated-and-associated-with-cellular-proliferation-in-colorectal-cancer
#16
Suguru Hayase, Kensuke Kumamoto, Katsuharu Saito, Yasuhide Kofunato, Yu Sato, Hirokazu Okayama, Kotaro Miyamoto, Shinji Ohki, Seiichi Takenoshita
Previous studies have shown that the L-type amino acid transporter 1 (LAT1) is highly expressed in many types of cancer. Upregulated LAT1 expression is considered to be associated with cancer cell proliferation. In the present study, we investigated LAT1 expression in 210 patients with colorectal cancer (CRC) and 40 patients with colonic adenoma using an immunohistochemical method, and analyzed the associations between LAT1 expression and clinicopathological factors and prognosis. The biological significance of LAT1 was also examined under conditions with sub-normal amounts of essential amino acids using colon cancer cell lines...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343687/mechanically-sensitive-mirnas-bias-human-mesenchymal-stem-cell-fate-via-mtor-signalling
#17
Jessica E Frith, Gina D Kusuma, James Carthew, Fanyi Li, Nicole Cloonan, Guillermo A Gomez, Justin J Cooper-White
Mechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In vitro, variations in matrix mechanics invoke changes in MSC proliferation, migration and differentiation. However, when incorporating MSCs within injectable, inherently soft hydrogels, this dominance over MSC response substantially limits our ability to couple the ease of application of hydrogels with efficiently directed MSC differentiation, especially in the case of bone generation. Here, we identify differential miRNA expression in response to varying hydrogel stiffness and RhoA activity...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343616/rapamycin-activates-tgf-receptor-independently-of-its-ligand-implications-for-endothelial-dysfunction
#18
Ayumi A Miyakawa, Thais Girao-Silva, Jose E Krieger, Elazer R Edelman
Rapamycin, the macrolide immunosuppressant and active pharmaceutic in drug-eluting stents (DES), has a well-recognized anti-proliferative action that involves inhibition of the mTOR pathway after binding to the cytosolic protein FKBP12. TGF receptor-type I (TGFRI) spontaneous activation is inhibited by the association with FKBP12. We hypothesized that rapamycin, in addition to inhibition of mTOR signaling, activates TGFRI independent of TGFb. Human umbilical vein endothelial cells (HUVEC) were treated with rapamycin (10nmoL/L) and/or TGF-b RI kinase inhibitor (TGFRIi, 100nmoL/L) for 24 hours...
January 17, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29343514/trpm2-channel-mediated-regulation-of-autophagy-maintains-mitochondrial-function-and-promotes-gastric-cancer-cell-survival-via-the-jnk-signaling-pathway
#19
Shekoufeh Almasi, Barry E Kennedy, Mariam El Aghil, Andra M Sterea, Shashi Gujar, Santiago Partida-Sánchez, Yassine El Hiani
A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anticancer mechanism is key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells...
January 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29343513/using-genetic-buffering-relationships-identified-in-fission-yeast-to-reveal-susceptibilities-in-cells-lacking-hamartin-or-tuberin-function
#20
Ashyad Rayhan, Adam Faller, Ryan Chevalier, Alannah Mattice, Jim Karagiannis
Tuberous sclerosis complex is an autosomal dominant disorder characterized by benign tumors arising from the abnormal activation of mTOR signaling in cells lacking TSC1 (hamartin) or TSC2 (tuberin) activity. To expand the genetic framework surrounding this group of growth regulators, we utilized the model eukaryote Schizosaccharomyces pombe to uncover and characterize genes that buffer the phenotypic effects of mutations in the orthologous tsc1 or tsc2 loci. Our study identified two genes: fft3 (encoding a DNA helicase) and ypa1 (encoding a peptidyle-prolyl cis/trans isomerase)...
January 17, 2018: Biology Open
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