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https://www.readbyqxmd.com/read/28655071/melatonin-rescues-mesenchymal-stem-cells-from-senescence-induced-by-the-uremic-toxin-p-cresol-via-inhibiting-mtor-dependent-autophagy
#1
Seung Pil Yun, Yong-Seok Han, Jun Hee Lee, Sang Min Kim, Sang Hun Lee
p-Cresol, found at high concentrations in the serum of chronic kidney failure patients, is known to cause cell senescence and other complications in different parts of the body. p-Cresol is thought to mediate cytotoxic effects through the induction of autophagy response. However, toxic effects of p-cresol on mesenchymal stem cells have not been elucidated. Thus, we aimed to investigate whether p-cresol induces senescence of mesenchymal stem cells, and whether melatonin can ameliorate abnormal autophagy response caused by p-cresol...
June 27, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28654658/butyrate-modifies-intestinal-barrier-function-in-ipec-j2-cells-through-a-selective-upregulation-of-tight-junction-proteins-and-activation-of-the-akt-signaling-pathway
#2
Hui Yan, Kolapo M Ajuwon
The intestinal epithelial barrier, composed of epithelial cells, tight junction proteins and intestinal secretions, prevents passage of luminal substances and antigens through the paracellular space. Dysfunction of the intestinal barrier integrity induced by toxins and pathogens is associated with a variety of gastrointestinal disorders and diseases. Although butyrate is known to enhance intestinal health, its role in the protection of intestinal barrier function is poorly characterized. Therefore, we investigated the effect of butyrate on intestinal epithelial integrity and tight junction permeability in a model of LPS-induced inflammation in IPEC-J2 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28653601/dexmedetomidine-inhibits-osteosarcoma-cell-proliferation-and-migration-and-promotes-apoptosis-by-regulating-mir-520a-3p
#3
Xiaoyan Wang, Yongguang Xu, Xinlei Chen, Jianmin Xiao
This study aimed to investigate the effect of dexmedetomidine (DEX) on osteosarcoma (OS) cell line MG63 and to explorethe possible relationship between DEX and miR-520-3p in OS. The results showed that DEX could up-regulate miR-520-3p which directly targeted AKT1. Additionally, miR-520-3p also inhibited MG63 cell proliferation and migration, promoted apoptosis, and suppressed protein expressions of AKT, p-AKT, p-mTOR and p-ERK1/2. DEX can inhibit OS cell proliferation and migration, and promote apoptosis by up-regulating the expression level of miR-520a-3p...
June 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28653281/fingolimod-exerts-only-temporary-antiepileptogenic-effects-but-longer-lasting-positive-effects-on-behavior-in-the-wag-rij-rat-absence-epilepsy-model
#4
Antonio Leo, Rita Citraro, Nicola Amodio, Caterina De Sarro, Maria Eugenia Gallo Cantafio, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in 2 different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28652768/pi3k-akt-mtor-pathway-promotes-progestin-resistance-in-endometrial-cancer-cells-by-inhibition-of-autophagy
#5
Hua Liu, Liqin Zhang, Xuyan Zhang, Zhumei Cui
Endometrial cancer (EC) is now one of the most common malignant tumors in young women. In all, 90% of young patients with EC have a high expression of progesterone recep tor, can be treated with progestin, and have very good prognosis. However, some of the young EC patients are resistant to progestin, the mechanism of which is unclear. To illuminate the mechanism by which endometrial cells acquire progestin resistance, we treated Ishikawa cells by slowly increasing dosage of progestin and established a progestin-resistant cell subline...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28651104/autophagy-is-an-important-event-for-low-dose-cytarabine-treatment-in-acute-myeloid-leukemia-cells
#6
Liyun Chen, Pei Guo, Yunxiang Zhang, Xiaoyang Li, Peimin Jia, Jianhua Tong, Junmin Li
Cytarabine (Ara-c) has been an important agent in acute myeloid leukemia (AML) treatment for more than 40 years. While, the mechanisms underlying low dose cytarabine (LD Ara-c) is poorly understood. In this study, we investigated the therapeutic effect of LD Ara-C in vitro. U937 and HEL cell lines were treated with increasing dose of Ara-C and showed growth inhibition rates in a time and dose-dependent manner. Treatment with LD Ara-C (50nM) induced a time-dependent increase in expression of microtubule-associated protein light chain 3 (LC3) and beclin1, but degradation of sequestosome1 (p62) in both U937 and HEL cells...
June 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28650797/larp1-functions-as-a-molecular-switch-for-mtorc1-mediated-translation-of-an-essential-class-of-mrnas
#7
Sungki Hong, Mallory A Freeberg, Ting Han, Avani Kamath, Yao Yao, Tomoko Fukuda, Tsukasa Suzuki, John K Kim, Ken Inoki
The RNA binding protein, LARP1, has been proposed to function downstream of mTORC1 to regulate the translation of 5'TOP mRNAs such as those encoding ribosome proteins (RP). However, the roles of LARP1 in the translation of 5'TOP mRNAs are controversial and its regulatory roles in mTORC1-mediated translation remain unclear. Here we show that LARP1 is a direct substrate of mTORC1 and Akt/S6K1. Deep sequencing of LARP1-bound mRNAs reveal that non-phosphorylated LARP1 interacts with both 5' and 3'UTRs of RP mRNAs and inhibits their translation...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28650474/an-activating-mutation-of-gnb1-is-associated-with-resistance-to-tyrosine-kinase-inhibitors-in-etv6-abl1-positive-leukemia
#8
O Zimmermannova, E Doktorova, J Stuchly, V Kanderova, D Kuzilkova, H Strnad, J Starkova, M Alberich-Jorda, J H F Falkenburg, J Trka, J Petrak, J Zuna, M Zaliova
Leukemias harboring the ETV6-ABL1 fusion represent a rare subset of hematological malignancies with unfavorable outcomes. The constitutively active chimeric Etv6-Abl1 tyrosine kinase can be specifically inhibited by tyrosine kinase inhibitors (TKIs). Although TKIs represent an important therapeutic tool, so far, the mechanism underlying the potential TKI resistance in ETV6-ABL1-positive malignancies has not been studied in detail. To address this issue, we established a TKI-resistant ETV6-ABL1-positive leukemic cell line through long-term exposure to imatinib...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649994/membrane-binding-and-activation-of-lkb1-by-phosphatidic-acid-is-essential-for-development-and-tumour-suppression
#9
Giada Dogliotti, Lars Kullmann, Pratibha Dhumale, Christian Thiele, Olga Panichkina, Gudrun Mendl, Roland Houben, Sebastian Haferkamp, Andreas W Püschel, Michael P Krahn
The serine/threonine kinase LKB1 regulates various cellular processes such as cell proliferation, energy homeostasis and cell polarity and is frequently downregulated in various tumours. Many downstream pathways controlled by LKB1 have been described but little is known about the upstream regulatory mechanisms. Here we show that targeting of the kinase to the membrane by a direct binding of LKB1 to phosphatidic acid is essential to fully activate its kinase activity. Consequently, LKB1 mutants that are deficient for membrane binding fail to activate the downstream target AMPK to control mTOR signalling...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28647365/conjugated-linoleic-acid-prevents-age-induced-bone-loss-in-mice-by-regulating-both-osteoblastogenesis-and-adipogenesis
#10
Guanlin Lin, Huan Wang, Jun Dai, Xiao Li, Ming Guan, Shutao Gao, Qing Ding, Huaixi Wang, Huang Fang
Osteoporosis (OP) can increase the risk of bone fracture and other complications, which is a major clinical problem. Previous researches have revealed that conjugated linoleic acid (CLA) can promote the bone formation. But the mechanisms are not clear. Thus, we tested the hypothesis that CLA acts on bone formation might be via mTOR Complex1 (mTORC 1) pathway by in vitro and vivo assays. We studied the effect of CLA mix on MC3T3-E1 pre-osteoblasts differentiation into osteoblasts, and bone formation under osteoporotic conditions...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28647312/comparison-of-the-pi3k-akt-mtor-pathway-expression-profile-in-tumoral-versus-nontumoral-tissue-samples-from-heart-transplant-recipients
#11
Natalia Suárez-Fuentetaja, Gonzalo Barge-Caballero, Eduardo Barge-Caballero, Jorge Pombo-Otero, Nieves Domenech-García, María G Crespo-Leiro
No abstract text is available yet for this article.
June 21, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28645610/inhibition-of-mitochondrial-translation-effectively-sensitizes-renal-cell-carcinoma-to-chemotherapy
#12
Bo Wang, Aojin Song, Dan Yu, Ting Rao, Yuan Ruan, Xiaobin Yao
The functional importance of mitochondrial protein translation has been recently documented in the context of various cancers but not renal cell carcinoma (RCC). In lines with these efforts, our work demonstrates that mitochondrial translation inhibition by tigecycline or depletion of EF-Tu mitochondrial translation factor effectively targets RCC and significantly sensitizes RCC response to chemotherapy. We show that antibiotic tigecycline inhibits multiple biological functions of RCC, including growth, colony formation and survival...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28644386/capsaicin-induces-autophagy-and-apoptosis-in-human-nasopharyngeal-carcinoma-cells-by-downregulating-the-pi3k-akt-mtor-pathway
#13
Yu-Tsai Lin, Hung-Chen Wang, Yi-Chiang Hsu, Chung-Lung Cho, Ming-Yu Yang, Chih-Yen Chien
Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28642089/involvement-of-mapk-akt-gsk-3%C3%AE-and-ampk-mtor-signaling-pathways-in-protection-of-remote-glial-cells-from-axotomy-induced-necrosis-and-apoptosis-in-the-isolated-crayfish-stretch-receptor
#14
E V Berezhnaya, M Y Bibov, M A Komandirov, M A Neginskaya, M V Rudkovskii, A B Uzdensky
Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells...
June 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28641473/co-targeting-intracellular-ph-and-essential-amino-acid-uptake-cooperates-to-induce-cell-death-of-t-all-ll-cells
#15
Véronique Imbert, Marielle Nebout, Didier Mary, Hitoshi Endou, Michael F Wempe, Claudiu T Supuran, Jean-Yves Winum, Jean-François Peyron
Cancer cells reprogram their metabolism to optimize their growth and proliferation in the host microenvironment. For this purpose, they enhance the uptake of extracellular nutrients and deal with the metabolic waste products through the overexpression of numerous membrane proteins including amino-acid transporters (LAT1) and acid-base regulating enzymes, such as carbonic anhydrases (CAs). Here we describe the anti-tumoral effects of a new class of CAXII inhibitors, the glycosyl coumarins on T-ALL/LL cells. These effects appeared to be mediated through inhibition of mTOR/Akt pathway and c-myc downregulation...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#16
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28638267/synergistic-antitumor-effect-of-sorafenib-in-combination-with-atm-inhibitor-in-hepatocellular-carcinoma-cells
#17
Jianhua Liu, Yahui Liu, Lingyu Meng, Bai Ji, Daqing Yang
Background: Currently, sorafenib is the only systemic chemotherapy drug for advanced stage Hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicate that sorafenib alone has only moderate antitumor efficacy, and could not inhibit disease metastasis and progression. KU-55933 is a specific ATM inhibitor, which has pro-apoptotic effect on tumor cells. In this study, we analyzed the synergistic effect of sorafenib and KU-55933 on the proliferation of HCC cell lines. Methods: Three HCC cell lines were treated with sorafenib and KU-55933 alone or combination in vitro to investigate inhibitory effect by MTT and wound healing assay...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28634451/berberine-ameliorates-diabetes-associated-cognitive-decline-through-modulation-of-aberrant-inflammation-response-and-insulin-signaling-pathway-in-dm-rats
#18
Qingjie Chen, Ran Mo, Ninghua Wu, Xin Zou, Cai Shi, Jing Gong, Jingbin Li, Ke Fang, Dingkun Wang, Deshen Yang, Kaifu Wang, Juan Chen
Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer's disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28634282/genomic-alterations-in-fatal-forms-of-non-anaplastic-thyroid-cancer-identification-of-med12-and-rbm10-as-novel-thyroid-cancer-genes-associated-with-tumor-virulence
#19
Tihana Ibrahimpasic, Bin Xu, Iñigo Landa, Snjezana Dogan, Sumit Middha, Venkatraman Seshan, Shyamprasad Deraje Vasudeva, Diane Carlson, Jocelyn Migliacci, Jeffrey A Knauf, Brian R Untch, Michael F Berger, Luc Gt Morris, R Michael Tuttle, Timothy A Chan, James A Fagin, Ronald Ghossein, Ian Ganly
Purpose. Patients with anaplastic thyroid cancer have a very high death rate. In contrast, deaths from non-anaplastic thyroid cancer are much less common. The genetic alterations in fatal non-anaplastic thyroid cancers have not been reported. <p>Experimental Design. We performed next-generation sequencing of 410 cancer genes from 57 fatal non-anaplastic thyroid primary cancers. Results were compared to The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC) and to the genomic changes reported in anaplastic thyroid cancer (ATC)...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28632723/mir-646-inhibited-cell-proliferation-and-emt-induced-metastasis-by-targeting-foxk1-in-gastric-cancer
#20
P Zhang, W M Tang, H Zhang, Y Q Li, Y Peng, J Wang, G N Liu, X T Huang, J J Zhao, G Li, A M Li, Y Bai, Y Chen, Y X Ren, G X Li, Y D Wang, S D Liu, J D Wang
BACKGROUND: MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated. METHODS: In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice...
June 20, 2017: British Journal of Cancer
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