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Guanghua Liu, Xin Zhao, Jingmin Zhou, Xiangming Cheng, Zixing Ye, Zhigang Ji
BACKGROUND/AIMS: Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. METHODS: RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance...
July 17, 2018: Cellular Physiology and Biochemistry
Erbo Dong, Alessandro Guidotti, Huaibo Zhang, Subhash C Pandey
Currently, the etiology of anxiety comorbid with alcohol use disorder (AUD) remains to be elucidated. Epidemiologic evidence suggests that individuals during their prenatal development may be especially vulnerable to the effects of environmental factors such as stress that predisposes them to psychiatric disorders including AUD later in life. To explore the cause of the comorbidity, we examined anxiety-like and alcohol drinking behaviors in adult offspring of prenatally stressed dam (referred as PRS-mice) using well-characterized paradigms-elevated plus maze (EPM), light/dark box (LDB) and two-bottle free-choice...
July 14, 2018: Neuropharmacology
Minghua Liu, Ge Zhao, Dan Zhang, Weixiao An, Honglin Lai, Xiaofang Li, Shousong Cao, Xiukun Lin
Previous studies by our group have demonstrated that extract of clove exhibits potent anticancer effects in vitro and in vivo. In the present study, the effect of an extracted and isolated active fraction of clove (AFC) on induction of cellular apoptosis in human colorectal cancer HCT-116 cells was investigated by morphological observation, flow cytometry, and western blotting analysis. The results revealed that AFC induced apoptosis of HCT-116 cells. AFC also induced autophagy, demonstrated by increased punctuate microtubule-associated protein 1A/1B-light chain 3 (LC3) staining, and LC3-II and Beclin-1 protein expression levels...
July 2, 2018: International Journal of Oncology
Hengli Zhao, Huifeng Jia, Qiuju Han, Jian Zhang
Homeobox containing 1 (HMBOX1) is a novel transcription repressor that is significantly downregulated in human liver cancer tissues and cell lines, but the exact biological function of HMBOX1 in liver cancer is still unknown. We observed a negative association between HMBOX1 expression level and the clinical stages of liver cancer. HMBOX1 also increased the LC3 II/LC3 I ratio, the endogenous autophagy marker, and inhibited the p38/AKT/mTOR pathway. Furthermore, cancer stem cell specific genes, including CD133, KLF4, ESG1 and SOX2, were significantly downregulated upon HMBOX1 overexpression...
July 10, 2018: Oncology Reports
Shuangshuang Yin, Shaonan Yang, Xudong Pan, Aijun Ma, Juanjuan Ma, Haotian Pei, Yi Dong, Shu Li, Wei Li, Xinran Bi
Endothelial cell autophagy has a protective role in inhibiting inflammation and preventing the development of atherosclerosis, which may be regulated by microRNA (miR)‑155. The present study aimed to investigate the mechanisms of autophagy in the development of atherosclerosis. Human umbilical vein endothelial cells model in vitro and using oxidized low‑density lipoprotein (ox‑LDL) stimulated cells to simulate the atherosclerosis. MiR‑155 mimics, miR‑155 inhibitors, and a negative control were respectively transfected in human umbilical vein endothelial cells to analyzed alterations in the expression of miR‑155...
June 29, 2018: Molecular Medicine Reports
Angela Burleigh, Nordau Kanigsberg, Joseph M Lam
The mTOR inhibitor rapamycin is used systemically for the treatment of vascular lesions. We report the first use of topical rapamycin for the successful treatment of two cases of tufted angioma. The evidence for the use of topical rapamycin in other dermatologic conditions is summarized to aid in clinical decision making on preparations and anticipated side effects.
July 17, 2018: Pediatric Dermatology
Amany S Mostafa, Khalid B Selim
A series of dihydropyrimidinone derivatives bearing various N-heterocyclic moieties was designed and synthesized. Twelve new compounds were screened for their cytotoxic activity using 60 cancer cell lines according to NCI (USA) protocol. Compound 19 showed a significant activity against NCI-H460, SK-MEL-5, and HL-60 (TB) cell lines with growth inhibition 88%, 86% and 85%, respectively, and was found to be more safe on normal cells when compared to doxorubicin. Enzyme inhibition assay was performed for compound 19 against mTOR (IC50  = 0...
July 5, 2018: European Journal of Medicinal Chemistry
Rong Du, Juan Du, Hao-Ming Tian, Tao Chen, Yun Gao, Yang Long, Dan Liu
OBJECTIVE: To investigate the influence of phenylalanine(Phe) on glucose uptake in mouse myoblast cell line C2C12 and to explore its relationship with mTOR-p70S6K pathway. METHODS: C2C12 cells were cultured to promote formation of multinucleated myotubes in vitro. The cells were deprived and incubated with Phe at different concentrations (1.25,2.5,5,10,20 mmol/L).Krebs-Ringer buffer (KRB) was used as control.The 2-NBDG was used to measure glucose uptake of C2C12...
May 2018: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Nana Song, Ting Zhang, XiaLian Xu, Zhihui Lu, Xiaofang Yu, Yi Fang, Jiachang Hu, Ping Jia, Jie Teng, Xiaoqiang Ding
Renal tubular injury and innate immune responses induced by hypoxia contribute to acute kidney injury. Accumulating evidence suggests that miR-21 overexpression protects against kidney ischemia injury. Additionally, miR-21 emerges as a key inhibitor in dendritic cell maturation. Thus, we hypothesized that miR-21 protects the kidney from IR injury by suppressing epithelial cell damage and inflammatory reaction. In this study, we investigated effects of miR-21 and its signaling pathways (PTEN/AKT/mTOR/HIF, PDCD4/NFκ-B) on kidney ischemia/reperfusion (IR) injury in vitro and in vivo ...
2018: Frontiers in Physiology
Fabrizio Marcucci, Cristiano Rumio
Tumor cells undergo epithelial-mesenchymal transition (EMT) or macroautophagy (hereafter autophagy) in response to stressors from the microenvironment. EMT ensues when stressors act on tumor cells in the presence of nutrient sufficiency, and mechanistic target of rapamycin (mTOR) appears to be the crucial signaling node for EMT induction. Autophagy, on the other hand, is induced in the presence of nutrient deprivation and/or stressors from the microenvironment with 5' adenosine monophosphate-activated protein kinase (AMPK) playing an important, but not exclusive role, in autophagy induction...
2018: Frontiers in Pharmacology
Na Wu, Ying Wan, Lu Song, Chen Qi, Zhenguo Liu, Jing Gan
Background: Levodopa-induced dyskinesia (LID) is a troublesome problem in the treatment of Parkinson's disease (PD). The mechanisms of LID are still mysterious. Recently, the interaction between Shp-2 and D1 dopamine receptor (D1R) has been identified to be indispensable in the D1R-mediated extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation and the occurrence of LID. However, the role of Shp-2 in the D1R-mediated signaling pathway of dyskinetic rat models is not fully clear...
2018: Neuropsychiatric Disease and Treatment
Genevieve P Hartley, Lyndah Chow, Dylan T Ammons, William H Wheat, Steven W Dow
Tumor-associated macrophages (TAMs) express PD-L1 and contribute to the immune-suppressive tumor microenvironment. Although the role of the PD-L1 and PD-1 interaction to regulate T-cell suppression is established, less is known about PD-L1 signaling in macrophages and how these signals may affect the function of TAM. We used in vitro and in vivo models to investigate PD-L1 signaling in macrophages and the effects of PD-L1 antibody treatment on TAM responses. Treatment of mouse and human macrophages with PD-L1 antibodies increased spontaneous macrophage proliferation, survival, and activation (costimulatory molecule expression, cytokine production)...
July 16, 2018: Cancer Immunology Research
Adrián González-González, Esperanza Muñoz-Muela, Juan A Marchal, Francisca Elvira Cara, Maria Pilar Molina, Marina Cruz-Lozano, Gema Jiménez, Akanksha Verma, Alberto Ramírez, Wei Qian, Wen Chen, Anthony J Kozielski, Olivier Elemento, M Dolores Martin-Salvago, Rafael Jesús Luque, Carmen Rosa-Garrido, David Landeira, María Quintana-Romero, Roberto R Rosato, María A García, César L Ramírez-Tortosa, Hanna Kim, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Anil K Sood, José A Lorente, Pedro Sánchez-Rovira, Jenny C Chang, Sergio Granados-Principal
PURPOSE: Based on the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFβ1. ATF4 is overexpressed in triple negative breast cancer (TNBC) patients, but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on breast cancer patient survival and TNBC aggressiveness, and the relationships between TGFβ and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature...
July 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sung-Min Lim, Sun-Hye Park, Joo-Hyoung Lee, Sun Hong Kim, Jee Yon Kim, Jeong-Ki Min, Gyun Min Lee, Yeon-Gu Kim
Sodium butyrate (NaBu) is an efficient supplement for increasing recombinant protein production in Chinese hamster ovary (CHO) cell culture. To elucidate the effects of NaBu on miRNA expression profile in recombinant CHO (rCHO) cells, differentially expressed miRNAs in NaBu-treated rCHO cells were assessed by NanoString nCounter analysis. This result showed that eight mature mouse miRNAs (let-7b, let-7d, miR-15b, miR-25, miR-27a, miR-99a, miR-125a-5p, and miR-125b-5p) were differentially expressed. Furthermore, quantitative real-time RT-PCR analysis of eight mature CHO miRNAs, annotated using a miRBase database, confirmed the transcriptomic findings...
July 13, 2018: Journal of Biotechnology
Zhuo Mao, Weizhen Zhang
The mammalian target of rapamycin, mTOR is the master regulator of a cell's growth and metabolic state in response to nutrients, growth factors and many extracellular cues. Its dysregulation leads to a number of metabolic pathological conditions, including obesity and type 2 diabetes. Here, we review recent findings on the role of mTOR in major metabolic organs, such as adipose tissues, liver, muscle, pancreas and brain. And their potentials as the mTOR related pharmacological targets will be also discussed...
July 13, 2018: International Journal of Molecular Sciences
Alex A Pyuen, Travis Meuten, Barbara J Rose, Douglas H Thamm
While extremely rare in humans, hemangiosarcoma (HSA) accounts for nearly 2% of canine neoplasia, and is characterized by both aggressive local growth/invasion and a high rate of metastasis. Both canine and human HSA exhibit sustained aberrant PI3K/Akt/mTOR pathway signaling. The purpose of this study was to examine the in vitro effects of a novel dual PI3K/mTOR inhibitor, VDC-597, in three canine HSA cell lines (DEN-, CIN-, and SB-HSA). VDC-597 suppressed activation of both Akt and 4eBP1 in canine HSA cells in a dose-dependent fashion, with an IC50 of approximately 0...
2018: PloS One
Paul Hwang, Darryn S Willoughby
It is widely established throughout the literature that skeletal muscle can induce hypertrophic adaptations following progressive overload of moderate to high-intensity resistance training. However, there has recently been a growing body of research that shows that the combination of blood flow restriction (BFR) with low intensity resistance exercise can induce similar gains in muscular strength and hypertrophic adaptations. The implementation of external pressure cuffs over the most proximal position of the limb extremities with the occlusion of venous outflow of blood distal to the occlusion site defines the BFR methodological protocol...
December 4, 2017: Journal of Strength and Conditioning Research
Fengjiao Zheng, Jingnan Han, Haocheng Lu, Changting Cui, Jichun Yang, Qinghua Cui, Jun Cai, Yong Zhou, Chaoshu Tang, Guoheng Xu, Bin Geng
Hydrogen sulfide (H2S) is an essential neuromodulator, generates by cystathionine β synthase (CBS) or 3-mecaptopyruvate sulfurtransferase (3MST) in the brain. H2S can mediate paraventricular nucleus (PVN) neuron activity, and regulate neuroendocrine hormones secretion. On the other hand, CBS deficiency caused metabolic disorder and body weight reduction. However, whether CBS/H2S of PVN regulates neuroendocrine hormones to mediate energy metabolism is unknown. Here, we first identified the CBS co-localization with thyrotropin-releasing hormone (TRH) and corticotropin releasing hormone (CRH) positive neurons...
July 12, 2018: Biochimica et Biophysica Acta
Theodora Tzanavari, Jason Tasoulas, Chrysoula Vakaki, Chrysovalantou Mihailidou, Gerasimos Tsourouflis, Stamatios Theocharis
Adipokines constitute a family of protein factors secreted by white adipose tissue (WAT), that regulate the functions of WAT and other sites. Leptin, adiponectin, resistin, are the main adipokines present in serum and saliva, targeting several tissues and organs, including vessels, muscles, liver and pancreas. Besides body mass regulation, adipokines affect glucose homeostasis, inflammation, angiogenesis, cell proliferation and apoptosis, and other crucial cell procedures. Their involvement in tumor formation and growth is well established and deregulation of adipokine and adipokine receptors' expression is observed in several malignancies including those located in the head and neck region...
July 13, 2018: Current Medicinal Chemistry
Wenjing He, Junhe Li
BACKGROUND: Exendin-4, one of the most widely used antidiabetic drugs, has recently been reported to have potential antitumor effects in cancers. Prostate cancer (PC) is one of the most common cancers in male patients with type 2 diabetes mellitus, and radiotherapy plays a vital role in the therapy of PC. Whether exendin-4 has the potential to enhance PC response to ionizing radiation (IR) remains unknown. We aimed to explore whether exendin-4 radiosensitizes PC cells. METHODS: GLP-1 receptor (GLP-1R) expression in PC tissue samples and cell lines were analyzed, Human prostate cancer cells (PC3 and LNCap) were treated with IR and exendin-4, and subjected to proliferation, clone formation, cell cycle, immunoblotting, and immunohistochemical analysis...
July 15, 2018: Prostate
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