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https://www.readbyqxmd.com/read/29458057/roles-of-the-insulin-signaling-pathway-in-insect-development-and-organ-growth
#1
Xianyu Lin, Guy Smagghe
Organismal development is a complex process as it requires coordination of many aspects to grow into fit individuals, such as the control of body size and organ growth. Therefore, the mechanisms of precise control of growth are essential for ensuring the growth of organisms at a correct body size and proper organ proportions during development. The control of the growth rate and the duration of growth (or the cessation of growth) are required in size control. The insulin signaling pathway and the elements involved are essential in the control of growth...
February 16, 2018: Peptides
https://www.readbyqxmd.com/read/29457836/deptor-suppresses-lipogenesis-and-ameliorates-hepatic-steatosis-and-acute-on-chronic-liver-injury-in-alcoholic-liver-disease
#2
Hanqing Chen, Feng Shen, Alex Sherban, Allison Nocon, Yu Li, Hua Wang, Ming-Jiang Xu, Xianliang Rui, Jinyan Han, Bingbing Jiang, Donghwan Lee, Na Li, Farnaz Keyhani-Nejad, Jian-Gao Fan, Feng Liu, Amrita Kamat, Nicolas Musi, Leonard Guarente, Pal Pacher, Bin Gao, Mengwei Zang
Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation and liver injury. Chronic-plus-binge ethanol feeding led to hyperactivation of mTORC1, as evidenced by increased phosphorylation of mTOR and its downstream kinase S6K1 in hepatocytes...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29456744/cardamonin-enhances-the-anti-proliferative-effect-of-cisplatin-on-ovarian-cancer
#3
Peiguang Niu, Daohua Shi, Shusheng Zhang, Yanting Zhu, Jintuo Zhou
The mammalian target of rapamycin (mTOR) is well-known as a promising therapeutic target in various cancer cells. mTOR activation decreases the sensitivity of ovarian cancer to cisplatin. Cardamonin inhibits the proliferation of various cancer cells by mTOR suppression. The present study examined whether cardamonin combined with cisplatin is efficacious for the anti-proliferation of ovarian cancer cells. The anti-proliferative effect was determined by MTT and cell cycle assays. Activation of the mTOR signal pathway and the expression of anti-apoptotic proteins were evaluated by western blot analysis...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456722/fucosterol-exhibits-selective-antitumor-anticancer-activity-against-hela-human-cervical-cell-line-by-inducing-mitochondrial-mediated-apoptosis-cell-cycle-migration-inhibition-and-downregulation-of-m-tor-pi3k-akt-signalling-pathway
#4
Hongye Jiang, Jie Li, Aiyue Chen, Yinguang Li, Meng Xia, Peng Guo, Shuzhong Yao, Shuqin Chen
Cervical cancer greatly contributes to cancer-associated mortalities worldwide. The growing incidence of cervical cancer is of primary concern, and has signaled the need for multiple treatment options. Despite preliminary responses to chemotherapy and/or surgical interventions, the tumors consistently relapse. Previously, natural products gained attention for their diverse bioactivities, which include however are not limited to, neuroprotective, antimicrobial and anticancer effects. The present study evaluated the anticancer activity of fucosterol against a panel of human cancer cell lines...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456672/roles-of-autophagy-in-androgen-induced-benign-prostatic-hyperplasia-in-castrated-rats
#5
Rong-Fu Liu, Guo Fu, Jian Li, Yu-Feng Yang, Xue-Gang Wang, Pei-De Bai, Yue-Dong Chen
The present study investigated the role of androgen in the process of androgen-induced prostate hyperplasia in castrated rats and assessed the role of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway in this process. Furthermore, the extent to which autophagy may affect the level of androgen-induced benign prostatic hyperplasia was also explored. A total of 40 Sprague Dawley rats were randomly divided into four groups: Testosterone group, rapamycin group, 3-methyladenine (3-MA) group, and control group...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29455662/the-role-of-rictor-downstream-of-receptor-tyrosine-kinase-in-cancers
#6
REVIEW
Ahlem Jebali, Nicolas Dumaz
The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been known for many years but the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway is only starting to emerge. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex 2) kinase activity and as such plays a key role downstream of RTK. Alterations of RICTOR have been identified in a number of cancer cell types and its involvement in tumorigenesis has begun to be unraveled recently...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454612/ecdysteroidogenesis-and-development-in-heliothis-virescens-lepidoptera-noctuidae-focus-on-ptth-stimulated-pathways
#7
Carmen Scieuzo, Marisa Nardiello, Rosanna Salvia, Marco Pezzi, Milvia Chicca, Marilena Leis, Sabino A Bufo, S Bradleigh Vinson, Asha Rao, Heiko Vogel, Patrizia Falabella
Post-embryonic development and molting in insects are regulated by endocrine changes, including prothoracicotropic hormone (PTTH)-stimulated ecdysone secretion by the prothoracic glands (PGs). In Lepidoptera, two pathways are potentially involved in PTTH-stimulated ecdysteroidogenesis, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/protein kinase B/target of rapamycin (PI3K/Akt/TOR). We investigated the potential roles of both these pathways in Heliothis virescens ecdysteroidogenesis...
February 15, 2018: Journal of Insect Physiology
https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#8
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29452162/pseudorabies-virus-induces-autophagy-to-enhance-viral-replication-in-mouse-neuro-2a-cells-in-vitro
#9
Changmeng Xu, Mi Wang, Zhongbao Song, Zhijian Wang, Qianyu Liu, Ping Jiang, Juan Bai, Yufeng Li, Xianwei Wang
Autophagy of cytoplasmic components plays an essential role in the pathogenic infection process. Furthermore, research suggests that autophagy is an extremely important component of the innate immune response. Our study aimed to reveal the effect of virus-induced autophagy on pseudorabies virus (PRV) replication. Our results confirmed that light chain 3 (LC3)-I was converted into LC3-II after PRV infection; this transition is considered an important indicator of autophagy. Transmission electron microscopy (TEM) revealed that PRV infection could notably increase the number of autophagosomes in mouse neuro-2a (N2a) cells...
February 13, 2018: Virus Research
https://www.readbyqxmd.com/read/29451277/tivozanib-a-new-treatment-option-for-renal-cell-carcinoma
#10
L Saes, F A L M Eskens
Tivozanib is a tyrosine kinase inhibitor that targets all vascular endothelial growth factor receptors (VEGFRs), causing inhibition of angiogenesis. It has recently been approved by the European Medicines Agency (EMA) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway inhibitor-naive, following disease progression after one prior treatment with cytokine therapy for advanced RCC. This review will focus on mechanisms of action, early drug development and results of published and ongoing clinical trials of tivozanib...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29451215/effect-of-moxibustion-on-mtor-mediated-autophagy-in-rotenone-induced-parkinson-s-disease-model-rats
#11
Shu-Ju Wang, Qi Wang, Jun Ma, Pei-Hao Yu, Zhong-Ming Wang, Bin Wang
Defects in autophagy-mediated clearance of α-synuclein may be one of the key factors leading to progressive loss of dopaminergic neurons in the substantia nigra. Moxibustion therapy for Parkinson's disease has been shown to have a positive effect, but the underlying mechanism remains unknown. Based on this, we explored whether moxibustion could protect dopaminergic neurons by promoting autophagy mediated by mammalian target of rapamycin (mTOR), with subsequent elimination of α-syn. A Parkinson's disease model was induced in rats by subcutaneous injection of rotenone at the back of their necks, and they received moxibustion at Zusanli (ST36), Guanyuan (CV4) and Fengfu (GV16), for 10 minutes at every point, once per day, for 14 consecutive days...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29449635/purkinje-cells-derived-from-tsc-patients-display-hypoexcitability-and-synaptic-deficits-associated-with-reduced-fmrp-levels-and-reversed-by-rapamycin
#12
Maria Sundberg, Ivan Tochitsky, David E Buchholz, Kellen Winden, Ville Kujala, Kush Kapur, Deniz Cataltepe, Daria Turner, Min-Joon Han, Clifford J Woolf, Mary E Hatten, Mustafa Sahin
Accumulating evidence suggests that cerebellar dysfunction early in life is associated with autism spectrum disorder (ASD), but the molecular mechanisms underlying the cerebellar deficits at the cellular level are unclear. Tuberous sclerosis complex (TSC) is a neurocutaneous disorder that often presents with ASD. Here, we developed a cerebellar Purkinje cell (PC) model of TSC with patient-derived human induced pluripotent stem cells (hiPSCs) to characterize the molecular mechanisms underlying cerebellar abnormalities in ASD and TSC...
February 15, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29449538/downregulation-of-perk-activity-and-eif2%C3%AE-serine-51-phosphorylation-by-mtor-complex-1-elicits-pro-oxidant-and-pro-death-effects-in-tuberous-sclerosis-deficient-cells
#13
Jothilatha Krishnamoorthy, Clara Tenkerian, Jyotsana Gupta, Nour Ghaddar, Shuo Wang, Cedric Darini, Kirk A Staschke, Abhishek Ghosh, Valentina Gandin, Ivan Topisirovic, Arnold S Kristof, Maria Hatzoglou, George Simos, Antonis E Koromilas
Oxidative stress determines cell fate through several mechanisms, among which regulation of mRNA translation by the phosphorylation of the alpha (α) subunit of the translation initiation factor eIF2α at serine 51 (eIF2αP) plays a prominent role. Increased eIF2αP can contribute to tumor progression as well as tumor suppression. While eIF2αP is increased in most cells to promote survival and adaptation to different forms of stress, we demonstrate that eIF2αP is reduced in tuberous sclerosis complex 2 (TSC2)-deficient cells subjected to oxidative insults...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449374/-time-resolved-analysis-of-amino-acid-stress-identifies-eif2-phosphorylation-as-necessary-to-inhibit-mtorc1-activity-in-liver
#14
Inna A Nikonorova, Emily T Mirek, Christina C Signore, Michael P Goudie, Ronald C Wek, Tracy G Anthony
Amino acid availability is sensed by general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1), but how these two sensors coordinate their respective signal transduction events remains mysterious. In this study we utilized mouse genetic models to investigate the role of GCN2 in hepatic mTORC1 regulation upon amino acid stress induced by a single injection of asparaginase. We found that deletion of Gcn2 prevented hepatic phosphorylation of eukaryotic initiation factor 2 alpha (eIF2) to asparaginase and instead unleashed mTORC1 activity...
February 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29448845/a-systematic-review-of-economic-evaluations-of-tyrosine-kinase-inhibitors-of-vascular-endothelial-growth-factor-receptors-mammalian-target-of-rapamycin-inhibitors-and-programmed-death-1-inhibitors-in-metastatic-renal-cell-cancer
#15
Panagiotis Petrou
The therapeutic categories of Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors, mammalian target of rapamycin inhibitors and Programmed Death-1 inhibitors have transformed the treatment of metastatic renal cell cancer. Nevertheless, this comes at an increased cost, in tandem with similar fiscal pressures in the broader oncology sector, which may jeopardize the sustainability of health systems. Areas covered To this direction, the economic evaluation of these agents is essential for rational and efficient resource allocation...
February 16, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29447985/selected-terpenes-from-leaves-of-ocimum-basilicum-l-induce-hemoglobin-accumulation-in-human-k562-cells
#16
Giordana Feriotto, Nicola Marchetti, Valentina Costa, Piera Torricelli, Simone Beninati, Federico Tagliati, Carlo Mischiati
Re-expression of fetal hemoglobin (HbF) was proposed as a possible therapeutic strategy for β-haemoglobinopathies. Although several inducers of HbF were tested in clinical trials, only hydroxyurea (HU) received FDA approval. Despite it produced adequate HbF levels only in half of HU-treated SCD patients, and was ineffective at all in β-thalassemia patients, beneficial effects of this approach suggested to continue in this direction identifying further molecules capable of inducing HbF. We tested the potential of essential oil isolated from Ocimum basilicum L...
February 13, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29447953/dendrite-growth-and-the-effect-of-ectopic-rheb-expression-on-cortical-neurons
#17
Aidan M Sokolov, Caitlin M Seluzicki, Mary C Morton, David M Feliciano
Ras homology enriched in brain (Rheb) is a GTPase that activates the protein kinase mammalian Target of Rapamycin (mTOR). Rheb mutations cause intellectual delay and megalencephaly. mTOR hyperactivation causes a constellation of neurodevelopmental disorders called "mTOR-opathies" that are frequently accompanied by hyperexcitable cortical malformations. Cortical malformations within the anterior cingulate cortex (ACC) and somatosensory cortex (SSC) frequently colocalize with hyperexcitability. Although Rheb and mTOR are implicated in the formation of cortical lesions, seizure activity, and defects in neuronal migration, the contribution of Rheb to changes in neuron size and dendrite morphology is not well established...
February 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29447354/creb3-regulatory-factor-mtor-autophagy-regulates-goat-endometrial-function-during-early-pregnancy
#18
Diqi Yang, Tingting Jiang, Jianguo Liu, Beibei Zhang, Pengfei Lin, Huatao Chen, Dong Zhou, Keqiong Tang, Aihua Wang, Yaping Jin
In domestic ruminants, a receptive endometrium is crucial for successful pregnancy. Although many essential molecular modulators and pathways have been identified during early pregnancy, the precise mechanisms regulating goat endometrial function remains largely unknown. Here, we describe a novel regulator during early pregnancy, whereby hormones increased CREB3 Regulatory Factor (CREBRF) expression and act as a potential activator of autophagy in endometrial epithelial cells (EECs) via the mTOR pathway. Our results showed that knockdown of CREBRF via shCREBRF hampered EECs proliferation by S-phase cell cycle arrest and significantly inhibited endometrial function...
February 13, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29447340/dysfunction-of-ddit4-in-the-decidua-is-relevant-to-the-pathogenesis-of-preeclampsia
#19
Jieqiong Yang, Yachao Zhang, Jing Tong, Hong Lv, Cong Zhang, Zi-Jiang Chen
Preeclampsia (PE) is a pregnancy-related disorder that occurs after 20 weeks of gestation and affects 3-5% of all human pregnancies worldwide. However, the pathogenesis of PE still remains poorly understood. A deficiency in decidualization is considered a contributing factor to the development of PE. The DNA damage inducible transcript 4 (DDIT4) gene encodes a protein whose main function is inhibiting mammalian target of rapamycin (mTOR) under stress, and several studies have demonstrated that its expression promotes tumor cell apoptosis...
February 13, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29446653/cgas-mediated-autophagy-protects-the-liver-from-ischemia-reperfusion-injury-independent-of-sting
#20
Zhao Lei, Meihong Deng, Zhongjie Yi, Qian Sun, Richard A Shapiro, Hongbo Xu, Tunliang Li, Patricia A Loughran, John E Griepentrog, Hai Huang, Melanie J Scott, Feizhou Huang, Timothy R Billiar
Liver ischemia/reperfusion (I/R) injury occurs through induction of oxidative stress and release of damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or from the nucleus. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING) and downstream type1 interferon (IFN-I) pathways, which are pivotal innate immune system responses to pathogen. However, little is known about the role of cGAS/STING in liver I/R injury...
February 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
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