Predictive metabolic signatures of end-stage renal disease: a multivariate analysis of population-based data.
es RD Abstract 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 ...
Source: Biochimie - June 15, 2018 Category: Biochemistry Authors: Silva RE, Baldim JL, Chagas-Paula DA, Soares MG, Lago JHG, Gonçalves RV, Novaes RD Tags: Biochimie Source Type: research

Peptidoglycan glycosyltransferase-ligand binding assay based on tryptophan fluorescence quenching.
Abstract Peptidoglycan glycosyltransferases (GTase) of family 51 are essential enzymes for the synthesis of the glycan chains of the bacterial cell wall. They are considered potential antibacterial target, but discovery of inhibitors was hampered so far by the lack of efficient and affordable screening assay. Here we used Staphylococcus aureus MtgA to introduce a single tryptophan reporter residue in selected positions flanking the substrates binding cavity of the protein. We selected a mutant (Y181W) that shows strong fluorescence quenching in the presence of moenomycin A and two lipid II analogs inhibitors. The ...
Source: Biochimie - June 14, 2018 Category: Biochemistry Authors: Dahmane I, Montagner C, Matagne A, Dumbre S, Herdewijn P, Terrak M Tags: Biochimie Source Type: research

Serotonin in the gut: Blessing or a curse.
Abstract 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. Recent studies revealed t...
Source: Biochimie - June 14, 2018 Category: Biochemistry Authors: Banskota S, Ghia JE, Khan WI Tags: Biochimie Source Type: research

SUMO1/sentrin/SMT3 specific peptidase 2 modulates target molecules and its corresponding functions.
Abstract Small ubiquitin-like modifier (SUMOylation) is a reversible post-translational modification, which plays important roles in numerous biological processes. SUMO could be covalently attached to target proteins in an isopeptide bond manner that occurs via a lysine ε-amino group on the target proteins and the glycine on SUMO C-terminus. This covalent binding could affect the subcellular localization and stability of target proteins. SUMO modification can be reversed by members of the Sentrin/SUMO-specific proteases (SENPs) family, which are highly evolutionarily conserved from yeast to human. SENP2, a...
Source: Biochimie - June 13, 2018 Category: Biochemistry Authors: Liu SL, Gao FH Tags: Biochimie Source Type: research

Screening and characterization of a Annenix A2 binding aptamer that inhibits the proliferation of myeloma cells.
Abstract Multiple myeloma (MM) is a malignant plasma cell disease and is considered incurable. Annexin A2 (ANXA2) is closely related to the proliferation and adhesion of MM. Using protein-SELEX, we performed a screen for aptamers that bind GST-ANXA2 from a library, and GST protein was used for negative selection. The enrichment of the ssDNA pool was monitored by filter-binding assay during selection. After nine rounds of screening and high-throughput sequencing, we obtained six candidate aptamers that bind to the ANXA2 protein. The affinities of the candidate aptamers for ANXA2 were determined by ELONA. Binding of...
Source: Biochimie - June 12, 2018 Category: Biochemistry Authors: Zhou W, Zhang Y, Zeng Y, Peng M, Li H, Sun S, Ma B, Wang Y, Ye M, Liu J Tags: Biochimie Source Type: research

Implication of oxysterols in chronic inflammatory human diseases.
Abstract A growing bulk of evidence suggests that cholesterol oxidation products, known as oxysterols, are potentially involved in the pathogenesis of major chronic diseases, including atherosclerosis, Alzheimer's disease, and inflammatory bowel disease. Oxysterols are involved in various key steps of these complex processes, mainly thanks to their ability to act through up-regulation of oxidative stress, inflammation, and cell toxicity. This review summarizes the current knowledge of the effects induced by these compounds on cells, after their accumulation in the arterial wall, brain, and intestine. This evidence...
Source: Biochimie - June 9, 2018 Category: Biochemistry Authors: Testa G, Rossin D, Poli G, Biasi F, Leonarduzzi G Tags: Biochimie Source Type: research

Emerging fields in chaperone proteins: a French workshop.
est O Abstract The "Bioénergétique et Ingénierie des Protéines (BIP)" laboratory, CNRS (France), organized its first French workshop on molecular chaperone proteins and protein folding in November 2017. The goal of this workshop was to gather scientists working in France on chaperone proteins and protein folding. This initiative was a great success with excellent talks and fruitful discussions. The highlights were on the description of unexpected functions and posttranslational regulation of known molecular chaperones (such as Hsp90, Hsp33, SecB, GroEL) and on state-of-the-art...
Source: Biochimie - June 8, 2018 Category: Biochemistry Authors: Mileo E, Ilbert M, Barducci A, Bordes P, Castanié-Cornet MP, Garnier C, Genevaux P, Gillet R, Goloubinoff P, Ochsenbein F, Richarme G, Iobbi-Nivol C, Giudici-Orticoni MT, Gontero B, Genest O Tags: Biochimie Source Type: research

Substituted Phosphonic Analogues of Phenylglycine as Inhibitors of Phenylalanine Ammonia Lyase from Potatoes.
Abstract A series of phosphonic acid analogues of phenylglycine variously substituted in phenyl ring have been synthesized and evaluated for their inhibitory activity towards potato L-phenylalanine ammonia lyase. Most of the compounds appeared to act as moderate (micromolar) inhibitors of the enzyme. Analysis of their binding performed using molecular modeling have shown that they might be bound either in active site of the enzyme or in the non-physiologic site. The latter one is located in adjoining deep site nearby the to the entrance channel for substrate into active site. PMID: 29890205 [PubMed - as suppl...
Source: Biochimie - June 8, 2018 Category: Biochemistry Authors: Wanat W, Talma M, Hurek J, Pawełczak M, Kafarski P Tags: Biochimie Source Type: research

G4RNA screener web server: User focused interface for RNA G-quadruplex prediction.
Abstract Though RNA G-quadruplexes became a focus of study over a decade ago, the main challenge associated with the identification of new potential G-quadruplexes remains a bottleneck step. It slows the study of these non-canonical structures in nucleic acids, and thus the understanding of their significance. The G4RNA screener is an accurate tool for the prediction of RNA G-quadruplexes but its deployment has brought to light an issue with its accessibility to G-quadruplex experts and biologists. G4RNA screener web server is a platform that provides a much needed interface to manage the input, parameters and res...
Source: Biochimie - June 6, 2018 Category: Biochemistry Authors: Garant JM, Perreault JP, Scott MS Tags: Biochimie Source Type: research

Consecutive Ribonucleoside Monophosphates on Template Inhibit DNA Replication by T7 DNA Polymerase or by T7 Polymerase and Helicase Complex.
Abstract rNTPs are structurally similar to dNTPs but are largely molar excessive in cell than dNTPs. rNTPs are inevitably incorporated into DNA to form rNMPs. Long RNA primers can also be incorporated into lagging-strand DNA. However, the influence of these incorporated rNMPs on T7 DNA replication remains unknown. In this work, we investigated primer extension past consecutive rNMPs (rA, r(AC), r(ACC), or r(ACCA)) on template by T7 DNA polymerase or by its complex with helicase. Primer extension is gradually inhibited with increasing rNMP number. rNMPs decrease the dNTP incorporation efficiency, slightly weaken th...
Source: Biochimie - June 5, 2018 Category: Biochemistry Authors: Zou Z, Chen Z, Cai Y, Yang H, Du K, Li B, Jiang Y, Zhang H Tags: Biochimie Source Type: research

Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.
Abstract The transformation of macrophages into lipid loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activa...
Source: Biochimie - June 5, 2018 Category: Biochemistry Authors: Banerjee D, Sinha A, Saikia S, Gogoi B, Rathore AK, Das AS, Pal D, Buragohain AK, Dasgupta S Tags: Biochimie Source Type: research

Enhanced expression and distinctive characterization of a long-acting FGF21 and its potential to alleviate nonalcoholic steatohepatitis.
Abstract We have previously constructed a novel polypeptide, PsTag, that should be useful in the development of biologics with properties comparable to those achievable by PEGylation, but with potentially less side effects. However, the low fermentation yields of polypeptide fusion proteins may limit the application of this technology. We suspected that when polypeptide fusion protein was expressed in E. coli, the corresponding 8 tRNAs were needed to transport a large number of repetitive 5 amino acids to the ribosomes and thus, resulting in a relative deficiency of these tRNAs. PsTag600-FGF21, a long-acting FGF21...
Source: Biochimie - June 2, 2018 Category: Biochemistry Authors: Yin J, Bao L, Chen R, Gao W, Gao X, Yao W Tags: Biochimie Source Type: research

Expression of long non-coding RNA LINC00973 is consistently increased upon treatment of colon cancer cells with different chemotherapeutic drugs.
Abstract Early prediction of tumor relapse depends on the identification of new prognostic cancer biomarkers, which are suitable for monitoring tumor response to different chemotherapeutic drugs. Using RNA-Seq, RT-qPCR, bioinformatics, and studies utilizing the murine tumor xenograft model, we have found significant and consistent changes in the abundance of five lincRNAs (LINC00973, LINC00941, CASC19, CCAT1, and BCAR4) upon treatment of both HT-29 and HCT-116 cells with 5-fluorouracil, oxaliplatin, and irinotecan at different doses and durations; both in vitro and in vivo. The most frequent changes were detected ...
Source: Biochimie - June 2, 2018 Category: Biochemistry Authors: Zinovieva OL, Grineva EN, Prokofjeva MM, Karpov DS, Zheltukhin AO, Krasnov GS, Snezhkina AV, Kudryavtseva AV, Chumakov PM, Mashkova TD, Prassolov VS, Lisitsyn NA Tags: Biochimie Source Type: research

Cysteine cathepsins as a prospective target for anticancer therapies-current progress and prospects.
Abstract Cysteine cathepsins (CTS), being involved in both physiological and pathological processes, play an important role in the human body. During the last 30 years, it has been shown that CTS are highly upregulated in a wide variety of cancer types although they have received a little attention as a potential therapeutic target as compared to serine or metalloproteinases. Studies on the increasing problem of neoplastic progression have revealed that secretion of cell-surface- and intracellular cysteine proteases is aberrant in tumor cells and has an impact on their growth, invasion, and metastasis by taking pa...
Source: Biochimie - June 2, 2018 Category: Biochemistry Authors: Pogorzelska A, Żołnowska B, Bartoszewski R Tags: Biochimie Source Type: research

Leishmania mexicana gp63 is the enzyme responsible for cyclooxygenase (COX) activity in this parasitic protozoa.
o TL, Talamás-Rohana P Abstract Cyclooxygenase-2 (COX-2) is an enzyme responsible of prostaglandins production, such as prostaglandin E2 (PGE2), an immune response modulator that regulates the immune system to inhibit Th1 and to promote Th2 cytokines production. Many parasites modulate their host immune response through PGE2 effects; however, in parasites, only one protein with COX activity has been described, the α-actinin of Entamoeba histolytica. Prostanoids production has been reported in some species of Leishmania but not the enzymes responsible of their production. To identify the protein respon...
Source: Biochimie - June 1, 2018 Category: Biochemistry Authors: Estrada-Figueroa LA, Díaz-Gandarilla JA, Hernández-Ramírez VI, Arrieta-González MM, Osorio-Trujillo C, Rosales-Encina JL, Alfredo TL, Talamás-Rohana P Tags: Biochimie Source Type: research

A novel fully human anti-CD47 antibody as a potential therapy for human neoplasms with good safety.
In this study, we further developed and assessed a novel fully human anti-CD47 antibody, AMMS4-G4, derived from ZF1 using affinity maturation. AMMS4-G4 exhibited equivalent anticancer effects with Hu5F9-G4, a humanized anti-CD47 antibody in clinical trial, on the potential of inducing significant phagocytosis of tumor cells in vitro and prolonging the survival of leukemia xenografted mice. Additionally, AMMS4-G4 significantly inhibited the growth of grafted solid tumors by enhancing macrophage infiltration and modestly enhanced the anti-tumor activity of opsonizing antibody and antiangiogenic therapy. In cynomolgus monkeys...
Source: Biochimie - June 1, 2018 Category: Biochemistry Authors: Yu XY, Qiu WY, Long F, Yang XP, Zhang C, Xu L, Chang HY, Du P, Hou XJ, Yu YZ, Zeng DD, Wang S, Sun ZW Tags: Biochimie Source Type: research

Secretome within the bone marrow microenvironment: A basis for mesenchymal stem cell treatment and role in cancer dormancy.
This article discusses the importance for parallel studies to determine how the same secretome may compromise safety during the use of stem cells in regenerative medicine. PMID: 29859990 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - May 31, 2018 Category: Biochemistry Authors: Eltoukhy HS, Sinha G, Moore C, Gergues M, Rameshwar P Tags: Biochimie Source Type: research

Diacylglycerol kinase δ controls down-regulation of cyclin D1 for C2C12 myogenic differentiation.
Diacylglycerol kinase δ controls down-regulation of cyclin D1 for C2C12 myogenic differentiation. Biochimie. 2018 May 30;: Authors: Sakai H, Murakami C, Matsumoto KI, Urano T, Sakane F Abstract Diacylglycerol kinase (DGK) is a lipid-metabolizing enzyme that phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). DGKδ is highly expressed in the skeletal muscle, and a decrease in DGKδ expression increases the severity of type 2 diabetes. However, the role of DGKδ in myogenic differentiation is still unknown. The present study demonstrated that DGKδ expression ...
Source: Biochimie - May 30, 2018 Category: Biochemistry Authors: Sakai H, Murakami C, Matsumoto KI, Urano T, Sakane F Tags: Biochimie Source Type: research

Exosomes in lung cancer diagnosis and treatment. From the translating research into future clinical practice.
Abstract Lung cancer is one of the main causes of cancer-related death worldwide. Despite advances in lung cancer pathophysiology, diagnosis and prognosis, a better understanding of the disease is strongly needed in order to establish novel diagnostic and therapeutic approaches that should improve treatment outcomes. Exosomes are a type of cell-secreted extracellular vesicles, which transfer a wide variety of biomolecules, such as proteins, mRNAs, microRNAs, and lipids, are implicated in intercellular communication and modulate tumor-host interactions. The potential value of exosomes and their contents in lung can...
Source: Biochimie - May 29, 2018 Category: Biochemistry Authors: Masaoutis C, Mihailidou C, Tsourouflis G, Theocharis S Tags: Biochimie Source Type: research

MyPMFs: a simple tool for creating statistical potentials to assess protein structural models.
Abstract Evaluating the model quality of protein structures that evolve in environments with particular physicochemical properties requires scoring functions that are adapted to their specific residue compositions and/or structural characteristics. Thus, computational methods developed for structures from the cytosol cannot work properly on membrane or secreted proteins. Here, we present MyPMFs, an easy-to-use tool that allows users to train statistical potentials of mean force (PMFs) on the protein structures of their choice, with all parameters being adjustable. We demonstrate its use by creating an accurate sta...
Source: Biochimie - May 29, 2018 Category: Biochemistry Authors: Postic G, Hamelryck T, Chomilier J, Stratmann D Tags: Biochimie Source Type: research

Quercetin inhibits glucose transport by binding to an exofacial site on GLUT1.
In this study, we confirm that quercetin is a competitive inhibitor of GLUT1 and also demonstrate that newly synthesized compounds, WZB-117 and BAY-876 are robust inhibitors of GLUT1 in L929 cells. To measure quercetin interaction with L929 cells, we develop a new fluorescent assay using flow cytometry. The binding of quercetin and its inhibitory effects on 2-deoxyglucose (2DG) uptake showed nearly identical dose dependent effects, with both having maximum effects between 50 and 100 μM and similar half maximum effects at 8.9 and 8.5 μM respectively. The interaction of quercetin was rapid with t1/2 of 54 s and t...
Source: Biochimie - May 29, 2018 Category: Biochemistry Authors: Hamilton KE, Rekman JF, Gunnink LK, Busscher BM, Scott JL, Tidball AM, Stehouwer NR, Johnecheck GN, Looyenga BD, Louters LL Tags: Biochimie Source Type: research

Secretome from SH-SY5Y APPSwe cells trigger time-dependent CHME3 microglia activation phenotypes, ultimately leading to miR-21 exosome shuttling.
In this study, we demonstrate that SH-SY5Y cells transfected with the Swedish mutant of APP695 (SHSwe) remarkably express increased inflammatory markers, combined with higher APP and Aβ1-40 production, when compared to naïve SH-SY5Y (SH) cells. Although exerting an early clearance effect on extracellular APP and Aβ accumulation when in co-culture with SHSwe cells, human CHME3 microglia gradually lose such property, and express both pro-inflammatory (iNOS, IL-1, TNF-α, MHC class II, IL-6) and pro-resolving genes (IL-10 and Arginase 1), while also evidence increased senescence-associated β-galactosi...
Source: Biochimie - May 29, 2018 Category: Biochemistry Authors: Fernandes A, Ribeiro AR, Monteiro M, Garcia G, Vaz AR, Brites D Tags: Biochimie Source Type: research

Trans-anethole ameliorates obesity via induction of browning in white adipocytes and activation of brown adipocytes.
In conclusion, TA possesses potential therapeutic implications for treatment of obesity by playing multiple modulatory roles in the induction of white fat browning, activation of brown adipocytes, and promotion of lipid catabolism. PMID: 29803631 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - May 24, 2018 Category: Biochemistry Authors: Kang NH, Mukherjee S, Min T, Kang SC, Yun JW Tags: Biochimie Source Type: research

Non-stereoselective decomposition of ( ±)-S-alk(en)yl-L-cysteine sulfoxides to antibacterial thiosulfinates catalyzed by C115H mutant methionine γ-lyase from Citrobacter freundii.
Non-stereoselective decomposition of (±)-S-alk(en)yl-L-cysteine sulfoxides to antibacterial thiosulfinates catalyzed by C115H mutant methionine γ-lyase from Citrobacter freundii. Biochimie. 2018 May 24;: Authors: Kulikova V, Morozova E, Rodionov A, Koval V, Anufrieva N, Revtovich S, Demidkina T Abstract S-Alk(en)yl-L-cysteine sulfoxides, initially found in plants of the genus Allium, are converted to antimicrobial thiosulfinates by pyridoxal 5'-phosphate(PLP)-dependent alliinase (EC 4.4.1.4). It was found that methionine γ-lyase (MGL, EC 4.4.1.11) catalyzes the β-elimination re...
Source: Biochimie - May 24, 2018 Category: Biochemistry Authors: Kulikova V, Morozova E, Rodionov A, Koval V, Anufrieva N, Revtovich S, Demidkina T Tags: Biochimie Source Type: research

Proteomic analysis of Tn-bearing glycoproteins from different stages of melanoma cells reveals new biomarkers.
This study was designed to identify Tn-carrying proteins and reveal their influence on cutaneous melanoma progression. We used a lectin-based strategy to purify Tn antigen-enriched cellular glycoproteome, the LC-MS/MS method to identify isolated glycoproteins, and the DAVID bioinformatics tool to classify the identified proteins. We identified 146 different Tn-bearing glycoproteins, 88% of which are new. The Tn-glycoproteome was generally enriched in proteins involved in the control of ribosome biogenesis, CDR-mediated mRNA stabilization, cell-cell adhesion and extracellular vesicle formation. The differential expression p...
Source: Biochimie - May 23, 2018 Category: Biochemistry Authors: Hoja-Łukowicz D, Szwed S, Laidler P, Lityńska A Tags: Biochimie Source Type: research

Chlorogenic acid ameliorates alcohol-induced liver injuries through scavenging reactive oxygen species.
In this study, we investigated the protective effects of CGA against liver injuries in vivo. Reduced alcohol-induced-steatosis, apoptotic cell death, and fibrosis due to reduced levels of oxidative stress were observed. These findings suggest that CGA treatment can be an effective approach to attenuate ALD through the suppression of oxidative stress. PMID: 29787793 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - May 19, 2018 Category: Biochemistry Authors: Kim H, Pan JH, Kim SH, Lee JH, Park JW Tags: Biochimie Source Type: research

Review article A translational view of cells' secretome analysis - from untargeted proteomic to potential circulating biomarkers.
Abstract The identification of circulating biomarkers capable of being used as routine for diagnosis, prognosis, risk stratification and therapeutic monitoring is still the major aim at clinical proteomics. However, the direct search in blood samples or other clinical relevant biofluids is frequently associated with technical limitations that makes the biomarker discovery process extremely difficult when using these types of samples. In this sense, the use of different approaches, such as the analysis of cells' secretomes, can be an important and promising complementary method for the identification and pre-select...
Source: Biochimie - May 18, 2018 Category: Biochemistry Authors: Anjo SI, Manadas B Tags: Biochimie Source Type: research

Type I collagen induces mesenchymal cell differentiation into myofibroblasts through YAP-induced TGF- β1 activation.
In conclusion, the three physicochemically distinct forms of col I induce the differentiation of mesenchymal cells into myofibroblasts through different pathways. PMID: 29777737 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - May 16, 2018 Category: Biochemistry Authors: Liu X, Long X, Liu W, Zhao Y, Hayashi T, Yamato M, Mizuno K, Fujisaki H, Hattori S, Tashiro SI, Ogura T, Atsuzawa Y, Ikejima T Tags: Biochimie Source Type: research

The direction of protein evolution is destined by the stability.
Abstract Protein evolution is potentially governed by protein stability. Here, we investigated the relationship between protein evolution and stability through the random mutational drift of a thermophilic bacterial protein, an esterase of Alicyclobacillus acidocaldarius (Aac-Est), at high and low temperatures. In the first random mutation of Aac-Est, few proteins exhibit increased activity at 65°C, indicating that the wild-type (WT) Aac-Est is located on the peak of a mountain in a fitness landscape for activity at high temperature. To obtain higher active variants than those of WT, it must go down the mounta...
Source: Biochimie - May 15, 2018 Category: Biochemistry Authors: Ota N, Kurahashi R, Sano S, Takano K Tags: Biochimie Source Type: research

Chromatography of oxysterols.
CHROMATOGRAPHY OF OXYSTEROLS. Biochimie. 2018 May 08;: Authors: Dias IHK, Wilson SR, Roberg-Larsen H Abstract Oxysterols play important roles in development and diseases, but can be highly challenging to analyze. To ensure satisfactory measurements, oxysterols must typically be separated with chromatography prior to detection. Here, we will devote attention to the chromatography of oxysterols, focusing on gas chromatography and liquid chromatography. We will present the role of stationary phases, mobile phases, and dimensions and geometries of particles/columns. We discuss how these parameters may aff...
Source: Biochimie - May 8, 2018 Category: Biochemistry Authors: Dias IHK, Wilson SR, Roberg-Larsen H Tags: Biochimie Source Type: research

The amyloidogenicity of a C-terminal region of TDP-43 implicated in Amyotrophic Lateral Sclerosis can be affected by anions, acetylation and homodimerization.
Abstract Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease associated with accumulation of hyper-phosphorylated, and ubiquitinated TAR DNA-binding protein-43 (TDP-43) as inclusion deposits in neuronal cells. Recently, amyloid-like fibrillar aggregates of TDP-43 have been reported from several ALS patients. The C-terminal region of TDP-43 is central to TDP-43's pathological aggregation and most of the familial ALS mutations in the encoding TARDBP gene are located in this domain. Also, aberrant proteolytic cleavages of TDP-43 produce cytotoxic C-terminal fragments of ∼15-35 kDa. The C-te...
Source: Biochimie - May 8, 2018 Category: Biochemistry Authors: Prasad A, Sivalingam V, Bharathi V, Girdhar A, Patel BK Tags: Biochimie Source Type: research

Importance of genetic background of oxysterol signaling in cancer.
Abstract Oxysterols, oxygenated derivatives of cholesterol, are formed in the human body or ingested. Experimental evidence suggests that due to their diverse functions, e.g. modulating the activity of receptors such as liver X receptors, oxysterol-binding and metabolizing proteins, and several ATP binding cassette transporters, oxysterols may contribute to a number of human disorders including cancer. Genetic variability of oxysterol pathways represents another side of this process, affecting carcinogenesis and cancer progression. This review summarizes information about both the physiological role of oxysterol p...
Source: Biochimie - May 7, 2018 Category: Biochemistry Authors: Holy P, Kloudova A, Soucek P Tags: Biochimie Source Type: research

Bioinformatics analyses and in vitro evidence for five and six stacked G-quadruplex forming sequences.
Pečinka P Abstract Quadruplexes are noncanonical DNA structures that arise in guanine rich loci and have important biological functions. Classically, quadruplexes contain four stacked intramolecular G-tetrads. Surprisingly, although some algorithms allow searching for longer than 4G tracts for quadruplex formation, these have not yet been systematically studied. Therefore, we analyzed the human genome for sequences that are predicted to adopt stacked intramolecular G-tetrads with greater than four stacks. The data provide evidence for numerous G-quadruplexes that contain five or six stacked intramolecular G-tetr...
Source: Biochimie - May 4, 2018 Category: Biochemistry Authors: Bartas M, Brázda V, Karlický V, Červeň J, Pečinka P Tags: Biochimie Source Type: research

Biological and regulatory roles of acid-induced small RNA RyeC in Salmonella Typhimurium.
Abstract Salmonella Typhimurium is an enteric pathogen that has evolved masterful strategies to enable survival under stress conditions both within and outside a host. The acid tolerance response (ATR) is one such mechanism that enhances the viability of acid adapted bacteria to lethal pH levels. While numerous studies exist on the protein coding components of this response, there is very little data on the roles of small RNAs (sRNAs). These non-coding RNA molecules have recently been shown to play roles as regulators of bacterial stress response and virulence pathways. They function through complementary base pai...
Source: Biochimie - May 3, 2018 Category: Biochemistry Authors: Ryan D, Mukherjee M, Nayak R, Dutta R, Suar M Tags: Biochimie Source Type: research

Exploring the biophysical properties of phytosterols in the plasma membrane for novel cancer prevention strategies.
Abstract Cancer is a global problem with no sign that incidences are reducing. The great costs associated with curing cancer, through developing novel treatments and applying patented therapies, is an increasing burden to developed and developing nations alike. These financial and societal problems will be alleviated by research efforts into prevention, or treatments that utilise off-patent or repurposed agents. Phytosterols are natural components of the diet found in an array of seeds, nuts and vegetables and have been added to several consumer food products for the management of cardio-vascular disease through t...
Source: Biochimie - May 3, 2018 Category: Biochemistry Authors: Fakih O, Sanver D, Kane D, Thorne JL Tags: Biochimie Source Type: research

Plasma oxysterol profiling in children reveals 24-hydroxycholesterol as a potential marker for Autism Spectrum Disorders.
Abstract Cholesterol and its oxygenated metabolites, such as oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorder. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, X-linked adrenoleukodystrophy, and Smith-Lemli-Opitz Syndrome. Recent studies have shown that Autism Spectrum Disorders are associated with disruption of cholesterol metabolism. The present study aimed at investigating the profile of oxysterols in plasma and their associati...
Source: Biochimie - May 3, 2018 Category: Biochemistry Authors: Grayaa S, Zerbinati C, Messedi M, HadjKacem I, Chtourou M, Ben Touhemi D, Naifar M, Ayadi H, Ayedi F, Iuliano L Tags: Biochimie Source Type: research

Unusual interaction of human apurinic/apyrimidinic endonuclease 1 (APE1) with abasic sites via the Schiff-base-dependent mechanism.
Abstract Clustered apurinic/apyrimidinic (AP) sites are more cytotoxic than isolated AP lesions because double strand breaks (DSB) can be formed during repair of closely positioned bistranded AP sites. Formation of DSB due to simultaneous cleavage of bistranded AP sites may be regulated by proteins specifically interacting with this complex lesion. A set of AP DNA duplexes containing AP sites in both strands in different mutual orientation (BS-AP DNAs) was used for search in the extracts of human cells proteins specifically recognizing clustered AP sites. A protein, which formed the Schiff-base-dependent covalent ...
Source: Biochimie - May 3, 2018 Category: Biochemistry Authors: Ilina ES, Khodyreva SN, Lavrik OI Tags: Biochimie Source Type: research

Phosphorylation-Induced Conformational Changes of Photoactivated Rhodopsin Probed by Fluorescent Labeling at Cys140 and Cys316.
G, Bubis J Abstract In order to monitor conformational changes following photoactivation and phosphorylation of bovine rhodopsin, the two reactive sulfhydryl groups at Cys140 and Cys316 were specifically labeled with the monobromobimane (mBBr) fluorophore. Although alterations in conformation after light exposure of rhodopsin were not detected by fluorescence excitation scans (300-450 nm) of the mBBr-labeled protein, the fluorescence signal was reduced ∼ 90% in samples containing photoactivated phosphorhodopsin. Predominant labeling at either Cys140 or Cys316 in light-activated and phosphorylated rhodopsin ...
Source: Biochimie - May 3, 2018 Category: Biochemistry Authors: Rodríguez S, Silva ML, Benaím G, Bubis J Tags: Biochimie Source Type: research

Sabellastarte magnifica Carboxypetidase Inhibitor: the first Kunitz inhibitor simultaneously interacting with carboxypeptidases and serine proteases.
es JR Abstract Multi-domain inhibitors capable to block the activity of different classes of proteases are not very common in nature. However, these kinds of molecules are attractive systems for biomedical or biotechnological applications, where two or more different targets need to be neutralized. SmCI, the Sabellastarte magnifica Carboxypeptidase Inhibitor, is a tri-domain BPTI-Kunitz inhibitor capable to inhibit serine proteases and A-like metallocarboxypeptidases. The BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases. SmCI is therefore, the only BPTI-Kuni...
Source: Biochimie - May 3, 2018 Category: Biochemistry Authors: Reytor González ML, Alonso-Del-Rivero Antigua M, Hedstrom L, Kuzmič P, Pires JR Tags: Biochimie Source Type: research

Notch3 is involved in adipogenesis of human adipose-derived stromal/stem cells.
Abstract Human adipose-derived stromal/stem cells (hASCs) have tremendous therapeutic potential and the ability to offer insight into human development and disease. Here we subject human ASCs to siRNA-mediated knockdown of Notch3 cultured under both self-renewing and adipogenic differentiation conditions. Self-renewal was monitored by assessing viability and proliferation rates through staining and alamarBlue assays, respectively. Adipogenesis was measured through Oil-Red O staining, western blot and quantitative real-time RT-PCR that determined expression levels of multipotency and adipogenic markers over time. N...
Source: Biochimie - April 27, 2018 Category: Biochemistry Authors: Sandel DA, Liu M, Ogbonnaya N, Newman JJ Tags: Biochimie Source Type: research

Ophiopogonin D improves osteointegration of titanium alloy implants under diabetic conditions by inhibition of ROS overproduction via Wnt/ β-catenin signaling pathway.
Ophiopogonin D improves osteointegration of titanium alloy implants under diabetic conditions by inhibition of ROS overproduction via Wnt/β-catenin signaling pathway. Biochimie. 2018 Apr 26;: Authors: Ma XY, Wen XX, Yang XJ, Zhou DP, Wu Q, Feng YF, Ding HJ, Lei W, Yu HL, Liu B, Xiang LB, Wang TS Abstract A high failure rate of titanium implants in diabetic patients has been indicated in clinical evidences. Excessive oxidative stress at the bone-implant interface plays an important role in the impaired osteointegration under diabetic conditions. While the underlying mechanisms remain unknown and t...
Source: Biochimie - April 26, 2018 Category: Biochemistry Authors: Ma XY, Wen XX, Yang XJ, Zhou DP, Wu Q, Feng YF, Ding HJ, Lei W, Yu HL, Liu B, Xiang LB, Wang TS Tags: Biochimie Source Type: research

Determination of the binding properties of p-cresyl glucuronide to human serum albumin.
Abstract p-Cresyl glucuronide (p-CG) is a by-product of tyrosine metabolism that accumulates in patients with end-stage renal disease. p-CG binding to human serum albumin in physiological conditions (37°C, pH 7.40) was studied by ultrafiltration (MWCO 10 kDa) and data were analyzed assuming one binding site. The estimated value of the association constant was 2.77×103 M-1 and a maximal stoichiometry of 3.80 mol per mole. At a concentration relevant for end-stage renal patients, p-CG was 23% bound to albumin. Competition experiments, using fluorescent probes, demonstrated that p-CG did not bind to S...
Source: Biochimie - April 26, 2018 Category: Biochemistry Authors: Yi D, Monteiro EB, Chambert S, Soula HA, Daleprane JB, Soulage CO Tags: Biochimie Source Type: research

Increase in liver cytosolic lipases activities and VLDL-TAG secretion rate do not prevent the non-alcoholic fatty liver disease in cafeteria diet-fed rats.
es VE Abstract We have previously shown that the cafeteria diet increases body fat mass, triacylglycerol (TAG) and insulin plasma levels, glucose uptake by white and brown adipose tissues, as well as the sympathetic activity to both adipose tissues in Wistar rats. The metabolic pathways responsible for the development of non-alcoholic fatty liver disease (NAFLD) were examined in cafeteria diet-fed rats. After 3 weeks offering cafeteria diet, we evaluated: (i) activity of the sympathetic nervous system by norepinephrine turnover rates; (ii) de novo fatty acid synthesis in vivo using 3H2O; (iii) secretion of very lo...
Source: Biochimie - April 26, 2018 Category: Biochemistry Authors: Fernandes de Melo A, Lima Moreira CC, Sales CF, Rentz T, Raposo HF, Rissato Garófalo MA, Botion LM, Kettelhut IDC, Franco de Oliveira HC, Chaves VE Tags: Biochimie Source Type: research

In vitro oxidized HDL and HDL from type 2 diabetes patients have reduced ability to efflux oxysterols from THP-1 macrophages.
Abstract Oxidized LDL (OxLDL) that are enriched in products of lipid peroxidation including oxysterols have been shown to induce cellular oxidative stress and cytotoxicity therefore accelerating atheroma plaque formation. Upon oxLDL exposure of THP-1 macrophages, intracellular oxidation of LDL derived-cholesterol as well as endogenous cholesterol was increased. The oxysterols intracellularly produced were efficiently exported to HDL whereas apolipoprotein A1 was inefficient. These findings prompted us to investigate the consequences of modification of HDL by oxidation and glycation as observed in type 2 diabetes w...
Source: Biochimie - April 26, 2018 Category: Biochemistry Authors: Chena Y, Arnal-Levron M, Hullin-Matsuda F, Knibbe C, Moulin P, Luquain-Costaz C, Delton I Tags: Biochimie Source Type: research

MiR-98 suppresses the effects of tumor-associated macrophages on promoting migration and invasion of hepatocellular carcinoma cells by regulating IL-10.
In conclusion, miR-98 not only regulated expression of inflammatory cytokines in HCC-conditioned TAMs, but also modulated the capacity of HCC-conditioned TAMs to regulate HepG2 cell migration and invasion, at least in part, by targeting IL-10. As a result, miR-98 may suppress the progress of HCC. PMID: 29702181 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - April 24, 2018 Category: Biochemistry Authors: Lei L, Pengfei S, Chengsheng Z, Zongchao L, Wuyuan Z Tags: Biochimie Source Type: research

Cellular mechanism of resistance of human colorectal adenocarcinoma cells against apoptosis-induction by Russell's Viper venom L-amino acid oxidase (Rusvinoxidase).
Abstract The present study highlights the cellular mechanism of resistance in human adenocarcinoma (Colo-205) cells against apoptosis induction by Rusvinoxidase, an L-amino acid oxidase purified from Russell's Viper venom (RVV). The significantly lower cytotoxicity as well as apoptotic activity of Rusvinoxidase towards Colo-205 cells (compared to MCF-7 breast cancer cells) is correlated with lower depletion of cellular glutathione content and increased down-regulation of catalase activity of Colo-205 cells following Rusvinoxidase treatment. Exposure to Rusvinoxidase subsequently diminished reactive oxygen species ...
Source: Biochimie - April 24, 2018 Category: Biochemistry Authors: Mukherjee AK, Saviola AJ, Mackessy SP Tags: Biochimie Source Type: research

The pericyte secretome: Potential impact on regeneration.
l G Abstract Personalized and regenerative medicine is an emerging therapeutic strategy that is based on cell biology and biomedical engineering used to develop biological substitutes to maintain normal function or restore damaged tissues and organs. The secretory capacities of different cell types are now explored as such possible therapeutic regenerative agents in a variety of diseases. A secretome can comprise chemokines, cytokines, growth factors, but also extracellular matrix components, microvesicles and exosomes as well as genetic material and may differ depending on the tissue and the stimulus applied to t...
Source: Biochimie - April 23, 2018 Category: Biochemistry Authors: Gaceb A, Barbariga M, Özen I, Paul G Tags: Biochimie Source Type: research

EBI2 - Sensor for Dihydroxycholesterol Gradients in Neuroinflammation.
Abstract Dihydroxycholesterols such as 7α,25-dihydroxysterols (7α,25-OHC) and 7α,27-OHC are generated from cholesterol by the enzymes CH25H, CYP7B1 and CYP27A1 in steady state but also in the context of inflammation. The G-protein coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2), also known as GPR183, senses these oxysterols and induces chemotactic migration of immune cells towards higher concentrations of these ligands. We recently showed that these ligands are upregulated in the CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis and that...
Source: Biochimie - April 21, 2018 Category: Biochemistry Authors: Kurschus F, Wanke F Tags: Biochimie Source Type: research

The effect of oxysterols on nerve impulses.
ard G Abstract The propagation of nerve impulses in myelinated nerve fibers depends on a number of factors involving the myelin and neural axons. In several neurodegenerative diseases, nerve impulses can be affected by the structural and biochemical characteristics of the myelin sheath and the activity of ion channels located in the nodes of Ranvier. Though it is generally accepted that lipid disorders are involved in the development of neurodegenerative diseases, little is known about their impact on nerve impulses. Cholesterol oxide derivatives (also called oxysterols), which are either formed enzymatically or a...
Source: Biochimie - April 20, 2018 Category: Biochemistry Authors: Bezine M, Namsi A, Sghaier R, Ben Khalifa R, Hamdouni H, Brahmi F, Badreddine I, Mihoubi W, Nury T, Vejux A, Zarrouk A, de Sèze J, Moreau T, Nasser B, Lizard G Tags: Biochimie Source Type: research

Functional characterization and molecular modeling of the mutations in CYP21A2 gene from patients with Congenital Adrenal Hyperplasia.
Abstract Steroid 21-Hydroxylase deficiency is an inherited autosomal recessive metabolic disorder of the adrenal steroidogenesis caused due to mutations in the CYP21A2 gene in 95% of CAH cases. Notably, the de novo mutations arise at the rate of 3-5%, therefore the functional characterization is of utmost importance for categorization of the novel mutations. Herein, we have functionally characterized the CYP21A2 missense mutations viz., p. F306V and p. H365 N. Notably, both the mutations were harbored by the patients exhibiting the non classical phenotype. We followed the approach of in vitro characterization of...
Source: Biochimie - April 20, 2018 Category: Biochemistry Authors: Khajuria R, Walia R, Bhansali A, Prasad R Tags: Biochimie Source Type: research