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Jessica Warns, Gurdeep Marwarha, Natalie Freking, Othman Ghribi
Colorectal cancer (CRC) is the third most diagnosed cancer in the western world, affecting 1 out of approximately 22 people in their lifetime. Several epidemiological studies suggest a positive association between high plasma cholesterol levels and colorectal cancer. However, the molecular mechanisms by which cholesterol may alter the risk of colorectal cancer (CRC) are ill-defined as the cholesterol lowering drugs statins do not appear to decrease a patient's risk of developing colorectal cancer. Cholesterol is metabolized to active derivatives including cholesterol oxidization products (COP), known as oxysterols, which have been shown to alter cellular proliferation...
July 13, 2018: Biochimie
A Chmurzynska, M A Mlodzik, A Radziejewska, A Szwengiel, A M Malinowska, J Nowacka-Woszuk
One-carbon metabolism is critical to pregnancy outcomes, because it determines the availability of nutrients involved in cell divisions and DNA methylation. The aim of this study was to analyze how 50% prenatal calorie restriction affected one-carbon metabolism in pregnant Wistar rats of the F0 to F2 generations. Mean choline (p < 0.001), betaine (p < 0.001), and S-adenosylmethionine (SAM) (p < 0.05) concentrations were respectively about 40%, 45%, and 20% lower in the F0_R (R - restricted diet) than in the F0_C (C - control diet)...
July 12, 2018: Biochimie
Amira Zarrouk, Yosra Ben Salem, Jawhar Hafsa, Randa Sghaier, Bassem Charfeddine, Khalifa Limem, Mohamed Hammami, Hatem Majdoub
Some oxysterols resulting either from enzymatic oxidation or autoxidation of cholesterol are associated with age-related diseases including neurodegenerative diseases. Among these oxysterols, 7β-hydroxycholesterol (7β-OHC) is often found at increased levels in patients. It is therefore important to identify molecules or mixtures of molecules to prevent 7β-OHC-induced side effects. Consequently, murine oligodendrocytes (158 N) were cultured in the absence or presence of 7β-OHC (20 μg/mL, 24 h) with or without a natural oil extracted from sea urchin (Paracentrotus lividus) eggs known for its biological activity...
July 9, 2018: Biochimie
Fatima Zohra Djeziri, Meriem Belarbi, Babar Murtaza, Aziz Hichami, Chahid Benammar, Naim Akhtar Khan
Obesity, triggered by high-fat diet (HFD), is associated to altered gustatory perception of dietary lipids. Oleanolic acid (OLA), a triterpene, has been reported to exert anti-obesity effects in animal models. Hence, we investigated the role of OLA in the modulation of oro-sensory perception of lipids in control and HFD-induced obese mice. As expected, OLA-treated obese mice exhibited a decrease in body, liver, and visceral adipose tissue weights. OLA treatment improved glucose tolerance, insulin level, plasma lipopolysaccharide (LPS), and hepatic cholesterol and triglyceride concentrations...
June 29, 2018: Biochimie
Robert C Monsen, John O Trent
Over the past two decades biologists and bioinformaticians have unearthed substantial evidence supporting a role for G-quadruplexes as important mediators of biological processes. This includes telomere damage signaling, transcriptional activity, and splicing. Both their structural heterogeneity and their abundance in oncogene promoters makes them ideal targets for drug discovery. Currently, there are hundreds of deposited DNA and RNA quadruplex atomic structures which have allowed researchers to begin using in silico drug screening approaches to develop novel stabilizing ligands...
June 29, 2018: Biochimie
Deepanshu Joshi, Debarshi Sarkar, Shio Kumar Singh
Orexin A (OXA), a hypothalamic neuropeptide, regulates food intake, sleep-wake cycle and energy balance by binding to its receptor (OX1R). Apart from brain, OXA and OX1R are also present in peripheral organs including reproductive tissues. Mammalian reproduction depends on uptake and proper utilization of glucose in the testes. This study, therefore, examined role of OXA/OX1R system in regulation of glucose homeostasis in adult mouse testis under in vivo and ex vivo conditions. Binding of OXA to OX1R was blocked using an OX1R antagonist, SB-334867...
June 29, 2018: Biochimie
Salvatore Nesci, Fabiana Trombetti, Vittoria Ventrella, Alessandra Pagliarani
Based on recent advances on the Ca2+ -activated F1 FO -ATPase features, a novel multistep mechanism involving the mitochondrial F1 FO complex in the formation and opening of the still enigmatic mitochondrial permeability transition pore (MPTP), is proposed. MPTP opening makes the inner mitochondrial membrane (IMM) permeable to ions and solutes and, through cascade events, addresses cell fate to death. Since MPTP forms when matrix Ca2+ concentration rises and ATP is hydrolyzed by the F1 FO -ATPase, conformational changes, triggered by Ca2+ insertion in F1 , may be transmitted to FO and locally modify the IMM curvature...
June 28, 2018: Biochimie
Jonas Abdel-Khalik, Peter J Crick, Eylan Yutuc, Andrea E DeBarber, P Barton Duell, Robert D Steiner, Ioanna Laina, Yuqin Wang, William J Griffiths
Dihydroxyoxocholestenoic acids are intermediates in bile acid biosynthesis. Here, using liquid chromatography - mass spectrometry, we confirm the identification of 7α,24-dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-dihydroxy-3-oxocholest-4-en-26-oic acids in cerebrospinal fluid (CSF) based on comparisons to authentic standards and of 7α,12α-dihydroxy-3-oxocholest-4-en-26-oic and 7α,x-dihydroxy-3-oxocholest-4-en-26-oic (where hydroxylation is likely on C-22 or C-23) based on exact mass measurement and multistage fragmentation...
June 27, 2018: Biochimie
Barouki R, Audouze K, Coumoul X, Demenais F, Gauguier D
Identifying precise and predictive biomarkers of health and disease is a critical objective of clinical biochemistry and biomedical research. New concepts and technologies have emerged recently that could support such an objective. The exposome corresponds to the totality of exposure over the lifetime. Research in this field allowed the development of sensors and biological biomarkers using omics technologies that are relevant for predicting the effect of those exposure on human health. Precision medicine has primarily focused on adapting treatments to the genetic profiles of tumors, when in fact, it had originally a wider scope including the use of robust biomarkers for disease prevention...
June 27, 2018: Biochimie
Rute S Araújo, Daniela F Santos, Gabriela A Silva
Secreted trophic factors are key to maintain the structural and functional integrity of the retina, as they regulate cellular pathways responsible for survival, function, and response to injury. Nevertheless, these same factors can also be involved in retinal pathologies, as a consequence of the impairment of the secretory function of cells. The cells considered as major contributors to the retinal secretome are the retinal pigmented epithelium (RPE) and Müller cells. Their role in the pathophysiology of the most common neovascular pathologies in the retina - Age-related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and Retinopathy of Prematurity (ROP) - is highlighted in this short review, together with current trophic factor-based therapies, which are mainly focused on controlling inflammation, cell survival, and angiogenesis...
June 27, 2018: Biochimie
Xin-Yi Fang, Hai Zhang, Lin Zhao, Shuai Tan, Qing-Cuo Ren, Lun Wang, Xiao-Fei Shen
1β-hydroxyl-5α-chloro-8-epi-xanthatin (XTT), a sesquiterpene lactone isolated from Xanthium sibiricum, possessed potent cytotoxicity on cancer cells in vitro. The objective of this study was to investigate the anti-tumor effect and underlying mechanisms of XTT on human hepatocellular carcinoma (HCC). Firstly, XTT inhibited the cell growth and induced apoptosis in human HCC cells, which was associated with the induction of Bax and cleaved-caspase-3, inhibition of Bcl-2 and survivin expression. Importantly, XTT induced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), and depletion of glutathione (GSH) in HCC cells through covalently modification of GSH...
June 27, 2018: Biochimie
G A O Ling, C H E N G Xiu-Lian, C A O Hua
The roles and mechanisms of long non-coding RNAs (lncRNA) in nasopharyngeal carcinoma (NPC) cells stemness and chemotherapeutic sensitivity are unclear. Here, Quantitative real-time PCR (qRT-PCR) was performed to detect the lncRNA THOR expression in NPC and normal adjacent tissues, adherent NPC cells and non-adherent NPC spheres, and we found that THOR was significantly increased in NPC tissues and non-adherent NPC spheres. Further in vitro and in vivo experiments were carried out and identified that knockdown of THOR attenuated NPC cells stemness, characterized as the decrease of spheres formation ability, cell proliferation, migration, invasion, stemness markers expression and tumor initiation, and enhanced cisplatin sensitivity of NPC cells...
June 26, 2018: Biochimie
Sebastien Desbois, Ulrik P John, Matthew A Perugini
The class I aldolase dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step of the diaminopimelate (DAP) lysine biosynthesis pathway in bacteria, archaea and plants. Despite the existence, in databases, of numerous fungal sequences annotated as DHDPS, its presence in fungi has been the subject of contradictory claims. We report the characterization of DHDPS candidates from fungi. Firstly, the putative DHDPS from Coccidioides immitis (PDB ID: 3QFE) was shown to have negligible enzyme activity...
June 26, 2018: Biochimie
Elena S Dyakonova, Vladimir V Koval, Alexander A Lomzov, Alexander A Ishchenko, Olga S Fedorova
Apurinic/apyrimidinic endonuclease Apn1 of Saccharomyces cerevisiae is known as a key player of the base excision DNA repair (BER) pathway in yeast. BER is initiated by DNA glycosylases, whereas Apn1 can start DNA repair individually in the nucleotide incision repair (NIR) pathway. The aim of this research was to elucidate kinetic and structural dynamic aspects of Apn1 involvement in the NIR process. One of the key characteristics of AP endonuclease's interactions is known to be divalent metal ions playing a part of a cofactor...
June 26, 2018: Biochimie
Dirk van Lier, Christopher Geven, Guus P Leijte, Peter Pickkers
Systemic inflammation plays a pivotal role in a multitude of conditions, including sepsis, trauma, major surgery and burns. However, comprehensive analysis of the pathophysiology underlying this systemic inflammatory response is greatly complicated by variations in the immune response observed in critically ill patients, which is a result of inter-individual differences in comorbidity, comedication, source of infection, causative pathogen, and onset of the inflammatory response. During experimental human endotoxemia, human subjects are challenged with purified endotoxin (lipopolysaccharide) intravenously which induces a short-lived, well-tolerated and controlled systemic inflammatory response, similar to that observed during sepsis...
June 21, 2018: Biochimie
Denis Sarrouilhe, Marc Mesnil
Besides its classical functions as a neurotransmitter in the central nervous system, local mediator in the gastrointestinal tract and vasoactive agent in the blood, serotonin has more recently emerged as a growth factor for human tumor cell lines of different origins (carcinomas, glioma and carcinoids). Several data are also available on serotonin involvement in cancer cell migration, metastatic dissemination and tumor angiogenesis. The serotonin-induced signaling pathways that promote tumor progression are complex and only partly understood in some cancer types...
June 21, 2018: Biochimie
Amira S Khan, Babar Murtaza, Aziz Hichami, Naim A Khan
The choice of food is governed largely by the sense of taste. To date, five basic taste modalities have been described; however, there is an increasing agreement on the existence of a 6th fat taste. The taste modalities might interact with each other and also with other senses. The advancements in cellular and molecular biology have helped the characterization of taste signaling mechanisms, down to the receptor level and beyond. CD36 and GPR120 have been shown to be involved in the detection of fat taste while bitter taste is perceived by a number of receptors that belong to a family of taste-type 2 receptors (T2R or TAS2R)...
June 21, 2018: Biochimie
Samar Kaddah, Nathalie Khreich, Fouad Kaddah, Lhoussain Khrouz, Catherine Charcosset, Hélène Greige-Gerges
Given that literature data may give inconsistent results on the effect of a drug on lipid membrane properties, this work aims to investigate the impact of the liposome composition and experimental protocol design on glucocorticoids (GRs: cortisol, cortisone, fludrocortisone acetate, methylprednisolone, prednisolone and prednisone)-modulating membrane fluidity and permeability. GRs-loaded liposomes consisting of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (CHOL) were prepared by reverse phase evaporation technique (REV) at DPPC:CHOL:GR molar ratios of 100:100:2...
June 20, 2018: Biochimie
Robson E Silva, João L Baldim, Daniela A Chagas-Paula, Marisi G Soares, João H G Lago, Reggiani V Gonçalves, Rômulo D Novaes
The variability of molecular signatures and predictive low molecular weight markers of chronic kidney disease (CKD) in different populations are poorly understood. Thus, in a large sample with 4763 people we compare the molecular signatures and metabolites with diagnostic relevance in plasma and urine of CKD patients of different geographical origins. From an integrated model based on dynamic networks and multivariate statistics, metabolites with predictive value obtained from targeted and untargeted molecular analysis, interactions between metabolic pathways affected by CKD, and the methodological quality of metabolomic studies were analyzed...
June 15, 2018: Biochimie
Suhrid Banskota, Jean-Eric Ghia, Waliul I Khan
Serotonin (5-hydroxytryptamine or 5-HT) once most extensively studied as a neurotransmitter of the central nervous system, is seen to be predominantly secreted in the gut. About 95% of 5-HT is estimated to be found in gut mainly within the enterochromaffin cells whereas about 5% is found in the brain. 5-HT is an important enteric signaling molecule and is well known for playing a key role in sensory-motor and secretory functions in the gut. In recent times studies uncovering various new functions of gut-derived 5-HT indicate that many more are yet to be discovered in coming days...
June 14, 2018: Biochimie
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