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p53 lipid

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https://www.readbyqxmd.com/read/28636657/novel-sirna-formulation-to-effectively-knockdown-mutant-p53-in-osteosarcoma
#1
Anup K Kundu, Swathi V Iyer, Sruti Chandra, Amit S Adhikari, Tomoo Iwakuma, Tarun K Mandal
OBJECTIVES: The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line. METHODS: The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer...
2017: PloS One
https://www.readbyqxmd.com/read/28614069/pegylated-lipid-bilayer-wrapped-nano-graphene-oxides-for-synergistic-co-delivery-of-doxorubicin-and-rapamycin-to-prevent-drug-resistance-in-cancers
#2
Raj Kumar Thapa, Jeong Hoon Byeon, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Nano-graphene oxide (nGO) is a carbon allotrope studied for its potential as carrier for chemotherapeutic delivery and its photoablation effects. However, interaction of nGO with blood components and the subsequent toxicities warrant a hybrid system for effective cancer drug delivery. Combination chemotherapy aids in effective cancer treatment and prevention of drug resistance. Therefore, in this study, we attempted to prepare polyethylene glycosylated (PEGylated) lipid bilayer-wrapped nGO co-loaded with doxorubicin (DOX) and rapamycin (RAPA), GOLDR, for the prevention and treatment of resistant cancers...
June 14, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28612525/-the-role-of-dna-double-strain-damage-repairing-mechanisms-in-diabetic-atheroscolersis
#3
Li Zeng, Qun-Fang Ding, Ting-Yuan Xu, Fang Luo, Ning Ge, Shi-Tong Li
OBJECTIVES: To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis. METHODS: Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively...
March 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28607433/lipidomic-analysis-of-skeletal-muscle-tissues-of-p53-knockout-mice-by-nuplc-esi-ms-ms
#4
Se Mi Park, Seul Kee Byeon, Hojun Lee, Hyerim Sung, Il Yong Kim, Je Kyung Seong, Myeong Hee Moon
Tumour suppressor p53 is known to be associated with the maintenance of mitochondrial functional properties in the skeletal muscles. As deactivation or mutation of p53 can affect the synthesis of lipids, investigating the relationship between p53-related energy generation metabolism and perturbation of lipid profile is critical. In this study, 329 lipid species (among 412 identified species) in two different skeletal muscle tissues (the gastrocnemius and soleus) from p53 knockout (KO) mice were quantitatively analysed using nanoflow ultrahigh performance liquid chromatography tandem mass spectrometry (nUPLC-MS/MS)...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595958/olive-phenolic-compounds-attenuate-deltamethrin-induced-liver-and-kidney-toxicity-through-regulating-oxidative-stress-inflammation-and-apoptosis
#5
Amina Maalej, Asma Mahmoudi, Zouhaier Bouallagui, Ines Fki, Rim Marrekchi, Sami Sayadi
The purpose of this study was to evaluate the protective effect of ethanolic olive fruit extract (OFE) and its phenolic compound, oleuropein (OLE), against hepato-renal toxicity induced by deltamethrin (DEM), a synthetic pyrethroid, in Wistar rats. The kidney and liver tissues were collected after 30 days of treatment for subsequent investigation. Rats that were given DEM had a highly significant elevation in the serum biomarkers as well as hepatic and renal levels of lipid peroxidation (MDA). Additionally, a significant reduction in the total antioxidant capacity (ABTS+), superoxide dismutase (SOD) and catalase (CAT) activities was noted...
June 15, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28588727/synergistic-cytotoxic-effects-of-a-combined-treatment-of-a-pinellia-pedatisecta-lipid-soluble-extract-and-cisplatin-on-human-cervical-carcinoma-in-vivo
#6
Mingxing Zhang, Yi Yu, Hongwei Zhang, Haixia Huang, Qingqing Cai, Yu Kang, Guiling Li, Congjian Xu
Herbal medicines are known to have numerous benefits, including lower toxicity and fewer side effects than traditional chemotherapeutic drugs. In traditional Chinese medicine, the rhizome of Pinellia pedatisecta (PE) Schott has long been used to treat cancer, undiagnosed swelling and erythema toxicum. However, its medical benefits lack support from scientific evidence. A novel lipid-soluble extract from PE has been previously verified to enhance the cytotoxicity of cis-dichlorodiammineplatinum-II (CDDP) against human cervical cancer cells in vitro...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28584302/crispr-cas9-mediated-p53-and-pten-dual-mutation-accelerates-hepatocarcinogenesis-in-adult-hepatitis-b-virus-transgenic-mice
#7
Yongzhen Liu, Xuewei Qi, Zhenzhen Zeng, Lu Wang, Jie Wang, Ting Zhang, Qiang Xu, Congle Shen, Guangde Zhou, Shaomin Yang, Xiangmei Chen, Fengmin Lu
The p53 mutation and altered Pten expression are two most common genetic events in Hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC). To confirm the causative role of p53 and Pten somatic mutation in HCC development, we established CRISPR/Cas9-mediated somatic gene disruption via hydrodynamic tail vein injection, allowing for in vivo targeting p53 and Pten simultaneously in adult HBV transgenic mice. Here we demonstrated that the utility of this approach resulted in macroscopic liver tumors as early as 4 months' post injection and most tumors harbored both p53 and Pten loss-of-function alterations...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28560444/schisandrin-b-attenuates-the-inflammatory-response-oxidative-stress-and-apoptosis-induced-by-traumatic-spinal-cord-injury-via-inhibition-of-p53-signaling-in-adult-rats
#8
D Q Xin, Z M Hu, H J Huo, X J Yang, D Han, W H Xing, Y Zhao, Q H Qiu
Schisandrin B is an active monomer of the Chinese magnolia vine (Schisandra chinensis) that can reduce transaminase activity in liver cells, inhibit lipid peroxidation, enhance antioxidant status, has protective effects in the liver and has antitumor effects. The present study investigated the potential protective effects of schisandrin B on the p53 signaling pathway in attenuating the inflammatory response, oxidative stress and apoptosis induced by traumatic spinal cord injury (TSCI) in adult rats. Behavioral examination, inclined plate test and spinal cord water content were used to evaluate the protective effect of schisandrin B in TSCI rats...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28542136/pak4-regulates-g6pd-activity-by-p53-degradation-involving-colon-cancer-cell-growth
#9
Xiumei Zhang, Xia Zhang, Yang Li, Yangguang Shao, Jianying Xiao, Ge Zhu, Feng Li
The p21-activated kinase 4 (PAK4) is overexpressed in different cancers and promotes proliferation of cancer cells. Reprogramming of glucose metabolism is found in most cancer cells which in turn supports rapid proliferation. However, the relationship between PAK4 and glucose metabolism in cancer cells has not been explored. In this study, we reported that PAK4 promoted glucose intake, NADPH production and lipid biosynthesis, leading to an increased proliferation of colon cancer cells. Mechanistically, PAK4 interacted with glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway and increased G6PD activity via enhancing Mdm2-mediated p53 ubiquitination degradation...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28533555/scopolin-ameliorates-high-fat-diet-induced-hepatic-steatosis-in-mice-potential-involvement-of-sirt1-mediated-signaling-cascades-in-the-liver
#10
Ahyoung Yoo, Vikram P Narayan, Eun Young Hong, Wan Kyunn Whang, Taesun Park
The present study aimed to investigate whether scopolin exhibits beneficial effects on high-fat diet (HFD)-induced hepatic steatosis in mice. The involvement of sirtuin 1 (SIRT1) as a molecular target for scopolin was also explored. Scopolin decreased the Km of SIRT1 for p53 and nicotinamide adenine dinucleotide without altering Vmax in a cell-free system. Scopolin alleviated oleic acid-induced lipid accumulation and downregulation of SIRT1 activity in HepG2 cells, and these beneficial effects of scopolin were abolished in the presence of SIRT1 inhibitor...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514055/caveolin-1-deficiency-induces-premature-senescence-with-mitochondrial-dysfunction
#11
Dong-Min Yu, Seung Hee Jung, Hyoung-Tae An, Sungsoo Lee, Jin Hong, Jun Sub Park, Hyun Lee, Hwayeon Lee, Myeong-Suk Bahn, Hyung Chul Lee, Na-Kyung Han, Jesang Ko, Jae-Seon Lee, Young-Gyu Ko
Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1(-/-) mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration...
May 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/28505155/oxidative-stress-and-expression-of-insulin-signaling-proteins-in-the-brain-of-diabetic-rats-role-of-nigella-sativa-oil-and-antidiabetic-drugs
#12
Mahmoud Balbaa, Shaymaa A Abdulmalek, Sofia Khalil
BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28496125/enhancing-specific-disruption-of-intracellular-protein-complexes-by-hydrocarbon-stapled-peptides-using-lipid-based-delivery
#13
D Thean, J S Ebo, T Luxton, Xue'Er Cheryl Lee, T Y Yuen, F J Ferrer, C W Johannes, D P Lane, C J Brown
Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28491867/metabolic-reprogramming-in-glioma
#14
REVIEW
Marie Strickland, Elizabeth A Stoll
Many cancers have long been thought to primarily metabolize glucose for energy production-a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28483521/sterol-regulatory-element-binding-protein-1-inhibitors-decrease-pancreatic-cancer-cell-viability-and-proliferation
#15
Siqingaowa, Sathiya Sekar, Venkat Gopalakrishnan, Changiz Taghibiglou
Sterol regulatory element-binding protein1 (SREBP1) is a key regulatory factor that controls lipid homeostasis. Overactivation of SREBP1 and elevated lipid biogenesis are considered the major characteristics in malignancies of prostate cancer, endometrial cancer, and glioblastoma. However, the impact of SREBP1 activation in the progression of pancreatic cancer has not been explored. The present study examines the effect of suppression of SREBP1 activation by its inhibitors like fatostatin and PF429242 besides analyzing the impact of inhibitory effects on SREBP1 downstream signaling cascade such as fatty acid synthase (FAS), hydroxymethylglutaryl-CoA reductase (HMGCoAR), stearoyl-CoA desaturase-1 (SCD-1), and tumor suppressor protein p53 in MIA PaCa-2 pancreatic cancer cells...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28480888/hepatic-p63-regulates-steatosis-via-ikk%C3%AE-er-stress
#16
Begoña Porteiro, Marcos F Fondevila, Teresa C Delgado, Cristina Iglesias, Monica Imbernon, Paula Iruzubieta, Javier Crespo, Amaia Zabala-Letona, Johan Fernø, Bárbara González-Terán, Nuria Matesanz, Lourdes Hernández-Cosido, Miguel Marcos, Sulay Tovar, Anxo Vidal, Julia Sánchez-Ceinos, Maria M Malagon, Celia Pombo, Juan Zalvide, Arkaitz Carracedo, Xabier Buque, Carlos Dieguez, Guadalupe Sabio, Miguel López, Patricia Aspichueta, María L Martínez-Chantar, Ruben Nogueiras
p53 family members control several metabolic and cellular functions. The p53 ortholog p63 modulates cellular adaptations to stress and has a major role in cell maintenance and proliferation. Here we show that p63 regulates hepatic lipid metabolism. Mice with liver-specific p53 deletion develop steatosis and show increased levels of p63. Down-regulation of p63 attenuates liver steatosis in p53 knockout mice and in diet-induced obese mice, whereas the activation of p63 induces lipid accumulation. Hepatic overexpression of N-terminal transactivation domain TAp63 induces liver steatosis through IKKβ activation and the induction of ER stress, the inhibition of which rescues the liver functions...
May 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28459365/interaction-of-renin-angiotensin-system-and-adenosine-monophosphate-activated-protein-kinase-signaling-pathway-in-renal-carcinogenesis-of-uninephrectomized-rats
#17
Ke-Ke Yang, Yi Sui, Hui-Rong Zhou, Hai-Lu Zhao
Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28450114/the-novel-cyclophilin-d-inhibitor-compound-19-protects-retinal-pigment-epithelium-cells-and-retinal-ganglion-cells-from-uv-radiation
#18
Laiqing Xie, Long Cheng, Guoxu Xu, Ji Zhang, Xiaoyan Ji, E Song
Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs...
June 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440512/astemizole-protects-against-human-umbilical-vein-endothelial-cell-injury-induced-by-hydrogen-peroxide-via-the-p53-signaling-pathway
#19
Jia-Nan Tian, Xiao-Dong Shi, Xiao-Kun Wang, Shuang Wang, Jing-Xue Xu, Chun-Xiao Yang
Astemizole has gained attention as an antineoplastic drug that targets important ion channels. The present study aimed to investigate the protective effects of astemizole against hydrogen peroxide (H2O2)‑induced oxidative damage to human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated with astemizole (0.5 and 1 µM) for 12 h, then exposed to H2O2 (200 µM) for 12 h. Cell viability was measured using the MTT assay. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px), reactive oxygen species (ROS) and apoptotic percentage were determined...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28402948/c-type-natriuretic-peptide-modified-lipid-vesicles-fabrication-and-use-for-the-treatment-of-brain-glioma
#20
Jia-Shuan Wu, Li-Min Mu, Ying-Zi Bu, Lei Liu, Yan Yan, Ying-Jie Hu, Jing Bai, Jing-Ying Zhang, Weiyue Lu, Wan-Liang Lu
Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo...
June 20, 2017: Oncotarget
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