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p53 AND beta cells

Yeter Topcu-Tarladacalisir, Melike Sapmaz-Metin, Turan Karaca
Curcumin has several biological functions particularly antioxidant and anti-inflammatory. The aims of this study are determination of the protective effects of curcumin on cisplatin-induced renal tubular cell apoptosis and related pathways in kidney. Eighteen male Wistar albino rats were randomly divided into three groups (n = 6): the control, cisplatin (CP), and cisplatin + curcumin (CP + CUR). Acute renal damage was induced by single dose of cisplatin (7.5 mg/kg) injected by intraperitoneally (i...
October 19, 2016: Renal Failure
Roi Isaac, Ido Goldstein, Noa Furth, Neta Zilber, Sarina Streim, Sigalit Boura-Halfon, Eytan Elhanany, Varda Rotter, Moshe Oren, Yehiel Zick
Earlier reported small interfering RNA (siRNA) high-throughput screens, identified seven-transmembrane superfamily member 3 (TM7SF3) as a novel inhibitor of pancreatic β-cell death. Here we show that TM7SF3 maintains protein homeostasis and promotes cell survival through attenuation of ER stress. Overexpression of TM7SF3 inhibits caspase 3/7 activation. In contrast, siRNA-mediated silencing of TM7SF3 accelerates ER stress and activation of the unfolded protein response (UPR). This involves inhibitory phosphorylation of eukaryotic translation initiation factor 2α activity and increased expression of activating transcription factor-3 (ATF3), ATF4 and C/EBP homologous protein, followed by induction of apoptosis...
October 14, 2016: Cell Death and Differentiation
Aihua Hou, Kai Pong Law, Min Qi Tin, Yoon Pin Lim, Louis Tong
Pterygium is a triangular shaped ocular fibrous surface lesion growing from conjunctiva towards central cornea, causing ocular irritation, astigmatism, and visual disturbance. The condition is characterized by epithelial proliferation, fibrovascular growth, chronic inflammation, and prominent extracellular matrix remodeling. Studies have suggested that aberrant extracellular proteins secreted by fibroblasts lead to abnormal matrix production and tissue invasion contributing to the development of the disease...
October 7, 2016: Experimental Eye Research
Guillaume Renner, Fanny Noulet, Marie-Cécile Mercier, Laurence Choulier, Nelly Etienne-Selloum, Jean-Pierre Gies, Maxime Lehmann, Isabelle Lelong-Rebel, Sophie Martin, Monique Dontenwill
The Wnt/beta catenin pathway has been highlighted as an important player of brain tumors aggressiveness and resistance to therapies. Increasing knowledges of the regulation of beta-catenin transactivation point out its hub position in different pathophysiological outcomes in glioma such as survival and migration. Crosstalks between integrins and beta-catenin pathways have been suggested in several tumor tissues. As we demonstrated earlier that α5β1 integrin may be considered as a therapeutic target in high grade glioma through its contribution to glioma cell migration and resistance to chemotherapy, we addressed here the potential relationship between α5β1 integrin and beta-catenin activation in glioma cells...
August 23, 2016: Oncotarget
Toru Nagao, Saman Warnakulasuriya, Hidenori Sakuma, Satoru Miyabe, Shogo Hasegawa, Junichiro Machida, Koji Suzuki, Hideo Fukano, Kazuo Shimozato, Shuji Hashimoto
BACKGROUND: We performed a randomized controlled chemoprevention trial of oral leukoplakia by administrating a low dose of beta-carotene and vitamin C supplements. 17% of subjects in the experimental arm (4/23) demonstrated clinical remission (complete or partial response) at completion of the trial. The objective of this study was to determine whether baseline expression of p53 and ki67 demonstrated any differences between those responding or not responding to our intervention. A secondary objective was to elucidate any relationship between dietary factors and clinical responses...
September 8, 2016: Journal of Oral Pathology & Medicine
Daniel Rusiecki, Boleslaw Lach, Branavan Manoranjan, Adam Fleming, Olufemi Ajani, Sheila K Singh
We report a childhood case of thalamic atypical extraventricular neurocytoma that progressed to highly anaplastic ganglioglioma (GG) after eight years of dormancy following subtotal resection and chemotherapy. The neurocytoma displayed immunoreactivity only for synaptophysin, beta-catenin, S-100 and CD56. The GG acquired strong immunoreactivity for chromogranin, glial fibrillary acidic protein, neuron specific enolase and p53 and showed a very high proliferation rate approaching 50% in some areas. Tumor transformation was associated with overexpression of components of the sonic hedgehog (Shh) and Wnt developmental signaling pathways, which are known to regulate tumor-initiating cells in malignant brain neoplasms...
September 2, 2016: Human Pathology
N B Ghate, A Das, D Chaudhuri, S Panja, N Mandal
The worldwide cancer incidences are remarkable despite the advancement in cancer drug discovery field, highlighting the need for new therapies focusing on cancer cell and its microenvironment, including inflammation. Several species of Drosera (family: Droseraceae) are used in various traditional as well as homeopathic systems of medicine. Drosera burmannii Vahl. is also enlisted in French Pharmacopoeia in 1965 for the treatment of inflammatory diseases, including chronic bronchitis, asthma and whooping cough...
2016: Cell Death Discovery
Aloísio Felipe-Silva, Alda Wakamatsu, Cinthya Dos Santos Cirqueira, Venâncio Avancini Ferreira Alves
AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC). METHODS: In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases...
July 21, 2016: World Journal of Gastroenterology: WJG
Qi Sun, Yu Dong, Huanyuan Wang, Kun Jiao, Jiahui Xu, Lu Ma, Haixia Huang, Huirong Liu, Wen Wang
Numerous studies have found that the age-associated structural and functional alterations in arteries were characterized by increased endothelial dysfunction. In this study, young (3 months), adult (9 months) and aging (20 months) male SD rats were randomly divided into six groups, including control groups and FeTMPyP (peroxynitrite scavenger) groups receiving saline and FeTMPyP respectively for 5 administrations once every 3 days via intraperitoneal injection. The aged-related proteins beta-galactosidase (β-gal), p53 and p16 as well as the nitrotyrosine and endothelium markers endothelial nitric oxide synthase (eNOS) and von Willebrand Factor (vWF) in vascular tissues were measured by immunohistochemistry...
July 16, 2016: Journal of Cardiovascular Pharmacology
Mariana Lopes Grassi, Camila de Souza Palma, Carolina Hassibe Thomé, Guilherme Pauperio Lanfredi, Aline Poersch, Vitor Marcel Faça
: Epithelial to mesenchymal transition (EMT) is a well-orchestrated process that culminates with loss of epithelial phenotype and gain of a mesenchymal and migratory phenotype. EMT enhances cancer cell invasiveness and drug resistance, favoring metastasis. Dysregulation of transcription factors, signaling pathways, miRNAs and growth factors including EGF, TGF-beta and HGF can trigger EMT. In ovarian cancer, overexpression of the EGFR family is associated with more aggressive clinical behavior...
July 6, 2016: Journal of Proteomics
Andrei Alexandru Constantinescu, Malak Abbas, Mohamad Kassem, Céline Gleizes, Guillaume Kreutter, Valerie Schini-Kerth, Ioan Liviu Mitrea, Florence Toti, Laurence Kessler
To examine and compare the mitochondria-related cellular mechanisms by which tacrolimus (TAC) or sirolimus (SIR) immunosuppressive drugs alter the pancreatic exocrine and endocrine β-cell fate. Human exocrine PANC-1 and rat endocrine insulin-secreting RIN-m5F cells and isolated rat islets were submitted to 1-100 nM TAC or SIR. In cultures, insulin secretion was measured as endocrine cell function marker. Apoptosis was quantified by annexin 5 and propidium iodide staining. Cleaved caspase-3, Bax apoptosis indicators, and p53, p21 cell cycle regulators were detected by Western blot...
July 2016: Molecular and Cellular Biochemistry
Elizabeth A Bonney, Kendall Krebs, George Saade, Talar Kechichian, Jayshil Trivedi, Yin Huaizhi, Ramkumar Menon
BACKGROUND: Human studies show that fetal membranes have a limited lifespan and undergo telomere-dependent cellular senescence that is augmented by oxidative stress and mediated by p38 mitogen activated protein kinase (MAPK). Further, these studies suggest that fetal membranes are anatomically and physiologically positioned to transmit senescence signals that may initiate parturition at term. METHODS: Longitudinal evaluation of feto-maternal tissues from mouse pregnancies was undertaken to determine the molecular progression of senescence during normal pregnancy...
July 2016: Placenta
Shakir D AlSharari, Salim S Al-Rejaie, Hatem M Abuohashish, Mohamed M Ahmed, Mohamed M Hafez
Background and Objective. High-cholesterol diet (HCD) intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p) which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia-induced hepatotoxicity in rats. Materials and Methods. Male Wistar rats were divided into four groups: G-I control, G-II Rutin, G-III HCD, and G-IV Rutin + HCD. The liver functions and lipid profile were used to evaluate the HCD-induced hepatotoxicity...
2016: Oxidative Medicine and Cellular Longevity
Y Li, T Zhang, Q Huang, Y Sun, X Chang, H Zhang, Y Zhu, X Han
Tumor suppressor p53 is a transcriptional factor that determines cell fate in response to multiple stressors, such as oxidative stress and endoplasmic reticulum stress, in the majority of cells. However, its role in pancreatic beta cells is not well documented. Our previous research has revealed that glycation-serum (GS) induced pancreatic beta-cell demise through the AGEs-RAGE pathway. In the present study, we investigated the role of p53 in GS-related beta-cell demise. Using pancreatic islets beta-cell line INS-1 cells, we found that with GS treatment, the transcriptional activity of p53 was significantly evoked due to the increased amount of nuclear p53 protein...
May 9, 2016: Endocrine
Zhang-Peng Li, Ru-Juan Xin, Hong Yang, Guo-Jun Jiang, Ya-Ping Deng, Dong-Jie Li, Fu-Ming Shen
Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing...
2016: Frontiers in Bioscience (Landmark Edition)
Hesham M Korashy, Ibraheem M Attafi, Mushtaq A Ansari, Mohammed A Assiri, Osamah M Belali, Sheik F Ahmad, Ibrahim A Al-Alallah, Fawaz E Al Anazi, Abdulqader A Alhaider
Gefitinib (GEF) is a multi-targeted tyrosine kinase inhibitor with anti-cancer properties, yet few cases of cardiotoxicity has been reported as a significant side effect associated with GEF treatment. The main purpose of this study was to investigate the potential cardiotoxic effect of GEF and the possible mechanisms involved using in vivo and in vitro rat cardiomyocyte model. Treatment of rat cardiomyocyte H9c2 cell line with GEF (0, 1, 5, and 10μM) caused cardiomyocyte death and upregulation of hypertrophic gene markers, such as brain natriuretic peptides (BNP) and Beta-myosin heavy chain (β-MHC) in a concentration-dependent manner at the mRNA and protein levels associated with an increase in the percentage of hypertrophied cardiac cells...
June 11, 2016: Toxicology Letters
Yifu Sun, Peng Xia, Haipeng Zhang, Biao Liu, Ying Shi
Osteosarcoma is the most common type of aggressive bone cancer. Current treatment strategies include surgical resection, radiation, and chemotherapy. Doxorubicin has been widely used as a chemotherapeutic drug to treat osteosarcoma. However, drug resistance has become a challenge to its use. In this study, p53-wild type U2OS and p53-null MG-63 osteosarcoma-derived cells were used to investigate the mechanism of doxorubicin-induced cytotoxicity. In cell viability assays, doxorubicin effectively induced apoptosis in U2OS cells via the p53 signaling pathway, evidenced by elevated PUMA and p21 protein levels and activated caspase 3 cleavage...
2016: American Journal of Cancer Research
Eric Samarut, Abdelhamid Bekri, Pierre Drapeau
How is the initial set of neurons correctly established during the development of the vertebrate central nervous system? In the embryo, glycine and GABA are depolarizing due the immature chloride gradient, which is only reversed to become hyperpolarizing later in post-natal development. We previously showed that glycine regulates neurogenesis via paracrine signaling that promotes calcium transients in neural stem cells (NSCs) and their differentiation into interneurons within the spinal cord of the zebrafish embryo...
2016: Frontiers in Molecular Neuroscience
Huimin Lu, Liuyi Hao, Songtao Li, Song Lin, Lin Lv, Yang Chen, Hongli Cui, Tianqi Zi, Xia Chu, Lixin Na, Changhao Sun
AIMS/HYPOTHESIS: Serum stearic acid (C18:0) is elevated in individuals with hyperlipidaemia and type 2 diabetes. However, the lipotoxicity induced by increased stearic acid in beta cells has not been well described. This study aimed to examine the adverse effects of stearic acid on beta cells and the potential mechanisms through which these are mediated. METHODS: Three groups of C57BL/6 mice were fed a normal diet or a high-stearic-acid/high-palmitic-acid diet for 24 weeks, respectively...
June 2016: Diabetologia
Mingyang Cai, Sewoon Kim, Kai Wang, Peggy J Farnham, Gerhard A Coetzee, Wange Lu
Genome-wide association studies (GWAS) have identified >100 independent susceptibility loci for prostate cancer, including the hot spot at 8q24. However, how genetic variants at this locus confer disease risk hasn't been fully characterized. Using circularized chromosome conformation capture (4C) coupled with next-generation sequencing and an enhancer at 8q24 as "bait", we identified genome-wide partners interacting with this enhancer in cell lines LNCaP and C4-2B. These 4C-identified regions are distributed in open nuclear compartments, featuring active histone marks (H3K4me1, H3K4me2 and H3K27Ac)...
2016: Scientific Reports
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