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  • MiR-204-5p promotes apoptosis and inhibits migration of osteosarcoma via targeting EBF2
    Biochimie (IF 3.188) Pub Date : 2018-12-06
    Mao Li, Yajun Shen, Qin Wang, Xuefeng Zhou

    Osteosarcoma is one of the most malignant cancer adolescents and young adults and metastatic osteosarcoma is a huge life threat with a 5-year survival lower than 20%. However, the mechanisms through which localized osteosarcoma turned metastatic are not fully understood. Here, we studied the role of miR-204-5p in osteosarcoma and found that miR-204-5p is downregulated in both osteosarcoma patients and osteosarcoma cell lines.In addition, overexpression of miR-204-5p resulted in increase of osteosarcoma cell apoptosis and decrease of osteosarcoma cell migration and invasion. Besides, our in vivo xenograft data showed strong inhibitory role of miR-204-5p in tumor growth. Importantly, our data showed that miR-204-5p regulates the mRNA stability of Early B Cell Factor 2 (EBF2), a crucial regulator in osteosarcoma apoptosis, by directly binding to 3’ UTR of EBF2. Besides, our data further revealed that overexpressed EBF2 inhibited apoptosis and facilitated migration and invasion of osteosarcoma cells. Additionally, EBF2 overexpression rescued the phenotype caused by miR-204-5p.Our data indicated that miR-204-5p is an anti-oncogenic miRNA in osteosarcoma which functions through inhibiting oncogenic transcription factor EBF2.These results provided new therapeutic targets for metastatic osteosarcoma and insights into molecular regulation of EBF2.

    更新日期:2018-12-07
  • Folate and choline absorption and uptake: Their role in fetal development
    Biochimie (IF 3.188) Pub Date : 2018-12-06
    Anna Radziejewska, Agata Chmurzynska

    Scope In this review, we attempt to assess how choline and folate transporters affect fetal development. We focus on how the expression of these transporters in response to choline and folate intake affects transport effectiveness. We additionally describe allelic variants of the genes encoding these transporters and their phenotypic effects. Methods and results We made an extensive review of recent articles describing role of choline and folate - with particularl emphasize on their transporters - in fetal development. Folate and choline are necessary for the proper functioning of the cell and body.During pregnancy, the requirements of these nutrients increase because of elevated maternal demand and the rapid division of fetal cells. The concentrations of folate and choline in cells depend on food intake, the absorption of nutrients, and the cellular transport system, which is tissue-specific and developmentally regulated. Relatively few studies have investigated the role of choline transporters in fetal development. Conclusions In this review we show relations between functioning of folate and choline transporters and fetal development.

    更新日期:2018-12-06
  • SOS genes contribute to Bac8c induced apoptosis-like death in Escherichia coli
    Biochimie (IF 3.188) Pub Date : 2018-12-05
    Heejeong Lee, Dong Gun Lee

    Antimicrobial peptides are one of the promising substitutes for conventional antibiotics. To examine their potential usefulness for controlling bacterial infections, the present study aimed to determine the induction of the self-destruction of Escherichia coli mediated by bac8c, which was modified from template peptide bactenecin. The potential of bac8c (RIWVIWRR) was reflected by the change in physiological following exposure, which led to the accumulation of reactive oxygen species (ROS) with an imbalance in the antioxidant system and damage to the intracellular lipids. In addition, bac8c-mediated death exhibited typical features to bacterial apoptosis-like death (ALD). The pathway was not enhanced in the absence of autocleavage of RecA and LexA, the SOS response proteins. We observed that elevated levels of intracellular ROS induced ALD, but this effect was insufficient before preceding RecA activation and LexA autocleavage. Furthermore, dinF, which encodes a member of the toxic compound extrusion (MATE) family, was evaluated to examine the role of the ALD pathway. dinF protein was required to accelerate the ALD-mediated bac8c in combination with RecA. Taken together, bac8c-mediated cell death underlies the severe SOS response, leading to RecA activation, LexA proteolysis, and dinF overexpression. Since then, overproduction of intracellular ROS facilitated the cell death.

    更新日期:2018-12-05
  • Endonuclease G modulates the alternative splicing of deoxyribonuclease 1 mRNA in human CD4+ T lymphocytes and prevents the progression of apoptosis
    Biochimie (IF 3.188) Pub Date : 2018-12-03
    Dmitry D. Zhdanov, Yulia A. Gladilina, Vadim S. Pokrovsky, Dmitry V. Grishin, Vladimir A. Grachev, Valentina S. Orlova, Marina V. Pokrovskaya, Svetlana S. Alexandrova, Anna A. Plyasova, Nikolay N. Sokolov

    Apoptotic endonucleases act cooperatively to fragment DNA and ensure the irreversibility of apoptosis. However, very little is known regarding the potential regulatory links between endonucleases. Deoxyribonuclease 1 (DNase I) inactivation is caused by alternative splicing (AS) of DNase I pre-mRNA skipping exon 4, which occurs in response to EndoG overexpression in cells. The current study aimed to determine the role of EndoG in the regulation of DNase I mRNA AS and the modulation of its enzymatic activity. A strong correlation was identified between the EndoG expression levels and DNase I splice variants in human lymphocytes. EndoG overexpression in CD4+ T cells down-regulated the mRNA levels of the active full-length DNase I variant and up-regulated the levels of the non-active spliced variant, which acts in a dominant-negative fashion. DNase I AS was induced by the translocation of EndoG from mitochondria into nuclei during the development of apoptosis. The DNase I spliced variant was induced by recombinant EndoG or by incubation with EndoG-digested cellular RNA in an in vitro system with isolated cell nuclei. Using antisense DNA oligonucleotides, we identified a 72-base segment that spans the adjacent segments of exon 4 and intron 4 and appears to be responsible for the AS. DNase I-positive CD4+ T cells overexpressing EndoG demonstrated decreased progression towards bleomycin-induced apoptosis. Therefore, EndoG is an endonuclease with the unique ability to inactivate another endonuclease, DNase I, and to modulate the development of apoptosis.

    更新日期:2018-12-03
  • Serotonergic neurotransmission manipulation for the understanding of brain development and function: learning from Tph2 genetic models
    Biochimie (IF 3.188) Pub Date : 2018-12-01
    Marta Pratelli, Massimo Pasqualetti

    Serotonin (5-hydroxytriptamine; 5-HT) is a fascinating neurotransmitter that thanks to an extensive axonal network is released throughout the entire central nervous system (CNS) and exerts its action on the modulation of a countless number of physiological, behavioral and cognitive processes. In addition, cumulating evidences have linked alteration in 5-HT neurotransmission with the onset of psychiatric and neurodevelopmental disorders, such as depression, autisms and schizophrenia. Nevertheless only 5% of the total body content of serotonin exerts its action in the CNS, while the rest is synthetized and stored in peripheral tissues where it acts as an autacoid. In 2003 it became evident that two distinct isoforms of tryptophan hydroxylase (Tph), the rate-limiting enzyme for the synthesis of serotonin, are selectively expressed in peripheral tissues and in the CNS, with Tph2 as the brain specific isoform. In the present review we describe how the discovery of Tph2 has improved our understanding on the role of serotonergic neurotransmission. We mainly focus on the analysis of animal models generated by genetic manipulation of Tph2, in which the synthesis of brain serotonin was either reduced or disrupted. The consequences of an altered serotonergic neurotransmission on brain development, as well as on physiological and behavioral processes will be assessed. Finally, we report on several association studies that have linked single nucleotide polymorphisms (SNPs) in the human TPH2 gene with behavioral disturbances and neuropsychiatric disorders.

    更新日期:2018-12-01
  • Oleate increase neutral lipid accumulation, cellular respiration and rescues palmitate-exposed GLP-1 secreting cells by reducing ceramide-induced ROS
    Biochimie (IF 3.188) Pub Date : 2018-12-01
    Stelia Ntika, Ketan Thombare, Masood Aryapoor, Hjalti Kristinsson, Peter Bergsten, Camilla Krizhanovskii

    Background Fatty acids (FAs), and especially monounsaturated FAs (MUFAs) stimulate GLP-1 release. However, lipotoxicity is indicated in GLP-1 secreting cells following long-term exposure to elevated levels of saturated FAs (SFAs) in vivo and in vitro, where in vitro studies indicate that cosupplementation with MUFAs confers lipoprotection. SFAs and MUFAs differentially affect the fate of cells in ways that depend on the cell type, concentration and ratio of the FAs. The present study was designed to further elucidate the mechanisms underlying the effects of SFAs/MUFAs on GLP-1-producing cells in terms of lipotoxicity/lipoprotection and GLP-1 secretion. Methods Cultured GLP-1 secreting cells were exposed to hyperlipidemia simulated by SFA-albumin complexes where the molar ratio was 2:1. The cellular response to simulated hyperlipidemia was assessed in the presence/absence of MUFA cosupplementation by determining intracellular ceramide, ROS, neutral lipid accumulation, and cellular respiration. The role for cellular respiration in GLP-1 secretion in response to SFAs/MUFAs was assessed. Results Generation of intracellular ceramide mediate a detrimental increased in ROS production following long term exposure to SFAs in GLP-1-secreting cells. Cosupplementation with MUFAs increases cellular respiration, triglyceride synthesis, and the expression of ceramide kinase, while reducing ceramide synthesis and attenuating ROS production, caspase-3 activity and DNA fragmentation. Further, acute secretory effects of unsaturated FAs are independent of FAO, but mediated by a FFAR1 induced increase in cellular respiration. Conclusion This study demonstrates novel data supporting effects of MUFAs on the ceramide biosynthetic pathway, triglyceride storage respiration and secretion in GLP-1 secreting cells. These findings may be of value for nutritional interventions, as well as for identification of novel targets, to help preserve L-cell mass and potentiate GLP-1 secretion in diabesity.

    更新日期:2018-12-01
  • Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells
    Biochimie (IF 3.188) Pub Date : 2018-12-01
    Pao-Lin Kuo, Jie-Yun Tseng, Hau-Ing Chen, Chia-Yun Wu, Hany A. Omar, Chia-Yih Wang, Han-Yi Cheng, Chao-Chin Hsu, Tzu-Fun Fu, Yen-Ni Teng

    SEPTIN12 (SEPT12) is a testis-enriched gene that is downregulated in the testis of infertile men with severe spermatogenic defects. While SEPT12 is involved in spermatogenic failure and sperm motility disorder, SEPT12 transcriptional regulation is still unknown. Here we report the promoter region of SEPT12 as a 245 bp segment upstream from the transcription start site. One androgen receptor (AR) and two of estrogen receptor α (ERα) binding sites were on this region were identified initially by Bioinformatics prediction and confirmed by chromatin immunoprecipitation assay. Truncated ERα or AR binding sites decreased the promoter activity, which indicated that the ERα and AR are essential for the SEPT12 promoter. On the other hand, the promoter activity was enhanced by the treatment with 17β-estradiol (E2) and 5α-dihydrotestosterone (5α-DHT). Thus, one androgen and two estrogen hormone responsive elements were in the promoter of SEPT12 gene to regulate the SEPT12 expression. Two single nucleotide polymorphisms (SNPs), rs759992 T>C and rs3827527 C>T, were observed in the SEPT12 gene promoter region and were able to decrease the promoter activity. In conclusion, the current work identified the promoter of the human SEPT12 gene and provided key evidence about its transcriptional regulation via E2 and 5α-DHT. Since SEPT12 has an important role in spermatogenesis, SEPT12 expression analysis can be developed as a potential tool for the assessment of environmental or food pollution by hormones or for the evaluation of the risk of endocrine-disrupting chemicals (EDCs) in general.

    更新日期:2018-12-01
  • Parametric study of immobilized cellulase-polymethacrylate particle for the hydrolysis of carboxymethyl cellulose
    Biochimie (IF 3.188) Pub Date : 2018-12-01
    Yi Wei Chan, Caleb Acquah, Eugene M. Obeng, Elvina C. Dullah, Jaison Jeevanandam, Clarence M. Ongkudon

    Biocarriers are pivotal in enhancing the reusability of biocatalyst that would otherwise be less economical for industrial application. Ever since the induction of enzymatic technology, varied materials have been assessed for their biocompatibility with enzymes of distinct functionalities. Herein, cellulase was immobilized onto polymethacrylate particles (ICP) as the biocarrier grafted with ethylenediamine (EDA) and glutaraldehyde (GA). Carboxymethyl cellulose (CMC) was used as a model substrate for activity assay. Enzyme immobilization loading was determined by quantifying the dry weight differential of ICP (pre-& post-immobilization). Cellulase was successfully demonstrated to be anchored upon ICP and validated by FTIR spectra analysis. The optimal condition for cellulase immobilization was determined to be pH 6 at 20 oC. The maximum CMCase activity was achieved at pH 5 and 50 oC. Residual activity of ∼50 % was retained after three iterations and dipped to ∼18 % on following cycle. Also, ICP displayed superior pH adaptability as compared to free cellulase. The specific activity of ICP was 65.14 ±1.11 % relative to similar amount of free cellulase.

    更新日期:2018-12-01
  • Serotonin in the gut: Blessing or a curse
    Biochimie (IF 3.188) Pub Date : 2018-06-14
    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. Recent studies revealed that 5-HT plays a pivotal role in immune cell activation and generation/perpetuation of inflammation in the gut. In addition to its various roles in the gut, there are now emerging evidences that suggest an important role of gut-derived 5-HT in other biological processes beyond the gut, such as bone remodeling and metabolic homeostasis. This review focuses to briefly summarize the accumulated and newly updated role of 5-HT in the maintenance of normal gut physiology and in the pathogenesis of inflammation in the gut. The collected information about this multifaceted signaling molecule may aid in distinguishing its good and bad effects which may lead to the development of novel strategies to overcome the unwanted effect, such as in inflammatory bowel disease.

    更新日期:2018-11-29
  • Serotonin and human cancer: A critical view
    Biochimie (IF 3.188) Pub Date : 2018-06-21
    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 cells 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. The results of several studies showed that serotonin levels in the tumor played a crucial role in cancer progression. A serotonin production and secretion by neuroendocrine cells have been shown in the progression of several solid tumors and the involvement of a serotoninergic autocrine loop was proposed. Specific receptor subtypes are associated with different fundamental stages of tumor progression and the pattern of receptors expression becomes dysregulated in several human tumors when compared with normal cells or tissues. Serotonin receptors, selective serotonin transporter and serotonin synthesis pathways are potential chemotherapeutic targets for the treatment of several cancers in which therapeutic approaches are limited. Through several asked questions, this critical mini-review discusses the relevance of the involvement of serotonin in human cancer progression.

    更新日期:2018-11-29
  • A cross-talk between fat and bitter taste modalities
    Biochimie (IF 3.188) Pub Date : 2018-06-22
    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). Hence, the most common role is played by TAS2R16 and TAS2R38 in bitter taste perception in humans. Increasing evidences from behavioural studies suggest that fat and bitter taste modalities might interact with each other, and this interaction might be critical in obesity. In the current review, we will discuss the evidence from genetic and behavioural studies and propose the molecular mechanism of a cross-talk between fat and bitter tastes.

    更新日期:2018-11-29
  • Experimental human endotoxemia as a model of systemic inflammation
    Biochimie (IF 3.188) Pub Date : 2018-06-22
    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. The human endotoxemia model can be conducted in a highly standardized and reproducible manner, using a carefully selected homogenous study population. As such, the experimental human endotoxemia model does not share the aforementioned clinical limitations and enables us to investigate both the mechanisms of systemic inflammation, as well as to evaluate novel (pharmacological) interventions in humans in vivo. The present review provides a detailed overview of the various designs, organ-specific changes, and strengths and limitations of the experimental human endotoxemia model, with the main focus on its use as a translational model for sepsis research.

    更新日期:2018-11-29
  • Fatty acids and oxidized lipoproteins contribute to autophagy and innate immunity responses upon the degeneration of retinal pigment epithelium and development of age-related macular degeneration
    Biochimie (IF 3.188) Pub Date : 2018-07-18
    Kai Kaarniranta, Ali Koskela, Szabolcs Felszeghy, Niko Kivinen, Antero Salminen, Anu Kauppinen

    Retinal pigment epithelium (RPE) damage is a primary sign in the development of age-related macular degeneration (AMD) the leading cause of blindness in western countries. RPE cells are exposed to chronic oxidative stress due to constant light exposure, active fatty acid metabolism and high oxygen consumption. RPE cells phagocytosize lipid rich photoreceptor outer segment (POS) which is regulated by circadian rhytmn. Docosahexaenoic acid is present in high quantity in POS and increases oxidative stress, while its metabolites have cytoprotective effects in RPE. During RPE aging, reactive oxygen species and oxidized lipoproteins are considered to be major causes of disturbed autophagy clearance that lead to chronic innate immunity response involved in NOD-Like, Toll-Like, Advanced Glycation End product Receptors (NLRP, TLR, RAGE, respectively), pentraxins and complement systems. We discuss role of fatty acids and lipoproteins in the degeneration of RPE and development of AMD.

    更新日期:2018-11-29
  • Cloning, purification and characterization of nigrelysin, a novel actinoporin from the sea anemone Anthopleura nigrescens
    Biochimie (IF 3.188) Pub Date : 2018-07-21
    Javier Alvarado-Mesén, Frank Solano-Campos, Liem Canet, Lohans Pedrera, Yadira P. Hervis, Carmen Soto, Henry Borbón, María E. Lanio, Bruno Lomonte, Aisel Valle, Carlos Alvarez

    Actinoporins constitute a unique class of pore-forming toxins found in sea anemones that being secreted as soluble monomers are able to bind and permeabilize membranes leading to cell death. The interest in these proteins has risen due to their high cytotoxicity that can be properly used to design immunotoxins against tumor cells and antigen-releasing systems to cell cytosol. In this work we describe a novel actinoporin produced by Anthopleura nigrescens, an anemone found in the Central American Pacific Ocean. Here we report the amino acid sequence of an actinoporin as deduced from cDNA obtained from total body RNA. The synthetic DNA sequence encoding for one cytolysin variant was expressed in BL21 Star (DE3) Escherichia coli and the protein purified by chromatography on CM Sephadex C-25 with more than 97% homogeneity as verified by MS-MS and HPLC analyses. This actinoporin comprises 179 amino acid residues, consistent with its observed isotope-averaged molecular mass of 19 661 Da. The toxin lacks Cys and readily permeabilizes erythrocytes, as well as L1210 cells. CD spectroscopy revealed that its secondary structure is dominated by beta structure (58.5%) with 5.5% of α-helix, and 35% of random structure. Moreover, binding experiments to lipidic monolayers and to liposomes, as well as permeabilization studies in vesicles, revealed that the affinity of this toxin for sphingomyelin-containing membranes is quite similar to sticholysin II (StII). Comparison by spectroscopic techniques and modeling the three-dimensional structure of nigrelysin (Ng) showed a high homology with StII but several differences were also detectable. Taken together, these results reinforce the notion that Ng is a novel member of the actinoporin pore-forming toxin (PFT) family with a HA as high as that of StII, the most potent actinoporin so far described, but with peculiar structural characteristics contributing to expand the understanding of the structure-function relationship in this protein family.

    更新日期:2018-11-29
  • A stochastic approach to serotonergic fibers in mental disorders
    Biochimie (IF 3.188) Pub Date : 2018-07-26
    Skirmantas Janušonis, Nils Detering

    Virtually all brain circuits are physically embedded in a three-dimensional matrix of fibers that release 5-hydroxytryptamine (5-HT, serotonin). The density of this matrix varies across brain regions and cortical laminae, and it is altered in some mental disorders, including Major Depressive Disorder and Autism Spectrum Disorder. We investigate how the regional structure of the serotonergic matrix depends on the stochastic behavior of individual serotonergic fibers and introduce a new framework for the quantitative analysis of this behavior. In particular, we show that a step-wise random walk, based on the von Mises-Fisher probability distribution, can provide a realistic and mathematically concise description of these fibers. We also consider other stochastic models, including the fractional Brownian motion. The proposed approach seeks to advance the current understanding of the ascending reticular activating system (ARAS) and may also support future theory-guided therapeutic approaches.

    更新日期:2018-11-29
  • Sphingolipid metabolism in non-alcoholic fatty liver diseases
    Biochimie (IF 3.188) Pub Date : 2018-07-31
    Marion Régnier, Arnaud Polizzi, Hervé Guillou, Nicolas Loiseau

    Non-alcoholic fatty liver disease (NAFLD) involves a panel of pathologies starting with hepatic steatosis and continuing to irreversible and serious conditions like steatohepatitis (NASH) and hepatocarcinoma. NAFLD is multifactorial in origin and corresponds to abnormal fat deposition in liver. Even if triglycerides are mostly associated with these pathologies, other lipid moieties seem to be involved in the development and severity of NAFLD. That is the case with sphingolipids and more particularly ceramides. In this review, we explore the relationship between NAFLD and sphingolipid metabolism. After providing an analysis of complex sphingolipid metabolism, we focus on the potential involvement of sphingolipids in the different pathologies associated with NAFLD. An unbalanced ratio between ceramides and terminal metabolic products in the liver and plasma promotes weight gain, inflammation, and insulin resistance. In the etiology of NAFLD, some sphingolipid species such as ceramides may be potential biomarkers for NAFLD. We review the clinical relevance of sphingolipids in liver diseases.

    更新日期:2018-11-29
  • The multifaceted functions of lipopolysaccharide in plant-bacteria interactions
    Biochimie (IF 3.188) Pub Date : 2018-08-02
    Alexander Kutschera, Stefanie Ranf

    In Gram-negative bacteria, the cell envelope largely consists of lipopolysaccharide (LPS), a class of heterogeneous glycolipids. As a fundamental component of the outer membrane, LPS provides stability to the bacterial cell and forms a protective cover shielding it from hostile environments. LPS is not only fundamental to bacterial viability, but also makes a substantial contribution both directly and indirectly to multiple aspects of inter-organismic interactions. During infection of animal and plant hosts, LPS promotes bacterial virulence but simultaneously betrays bacteria to the host immune system. Moreover, dynamic remodulation of LPS structures allows bacteria to fine-tune OM properties and quickly adapt to diverse and often hostile environments, such as those encountered in host tissues. Here, we summarize recent insights into the multiple functions of LPS in plant-bacteria interactions and discuss what we can learn from the latest advances in the field of animal immunity. We further pinpoint open questions and future challenges to unravel the different roles of LPS in the dynamic interplay between bacteria and plant hosts at the mechanistic level.

    更新日期:2018-11-29
  • Serotonin in stem cell based-dental repair and bone formation: A review
    Biochimie (IF 3.188) Pub Date : 2018-08-02
    Anne Baudry, Benoit Schneider, Jean-Marie Launay, Odile Kellermann

    Genetic and pharmacological studies provided evidence that serotonin (5-HT) is an important signaling molecule for the development and the maintenance of mineralized tissues. However, how 5-HT takes part to the homeostasis of teeth and bone remains elusive. In the dental field, a major breakthrough comes from the identification of 5-HT but also dopamine (DA) as "damage" signals necessary for stem cell-based tooth repair. Pulpal stem cells express the overall functions of 5-HT and DA neurons including a definite set of functional 5-HT/DA receptors that render cells responsive for circulating bioamines. Upon tooth injury, activated platelets release bulks of 5-HT/DA that mobilize pulpal stem cells for natural dental repair. The contribution of 5-HT to bone metabolism is more documented with description of both anabolic and resorptive effects. By controlling the tissue-non specific alkaline phosphatase (TNAP), 5-HT2B receptors exert an anabolic function and a pivotal role in mineralization processes. Increasing our understanding of the role of 5-HT receptors in bone metabolism may pave the road for the development of therapeutic strategies towards skeletal-associated pathologies and ectopic calcification.

    更新日期:2018-11-29
  • A chronic LPS-induced low-grade inflammation fails to reproduce in lean mice the impairment of preference for oily solution found in diet-induced obese mice
    Biochimie (IF 3.188) Pub Date : 2018-08-10
    Arnaud Bernard, Déborah Ancel, Patricia Passilly-Degrace, Jean-François Landrier, Laurent Lagrost, Philippe Besnard

    Diet-induced obesity (DIO) is associated with a decreased oral fat detection in rodents. This alteration has been explained by an impairment of the lipid-mediated signaling in taste bud cells (TBC). However, factors responsible for this defect remain elusive. Diet rich in saturated fatty acids is known to elicit a metabolic inflammation by promoting intestinal permeation to lipopolysaccharides (LPS), Gram-negative bacteria-derived endotoxins. To determine whether a local inflammation of the gustatory tissue might explain the obese-induced impairment of the oro-sensory detection of lipids, mice were subjected to a DIO protocol. Using a combination of behavioral tests, transcriptomic analyses of gustatory papillae and biochemical assays, we have found that i) DIO elicits a pro-inflammatory genic profile in the circumvallate papillae (CVP), known to house the highest density of lingual taste buds, ii) NFkB, a key player of inflammatory process, might play a role in this transcriptomic pattern, iii) plasma LPS levels are negatively correlated with the preference for oily solution, and iv) a chronic infusion of LPS at a level similar to that found in DIO mice is not sufficient to alter the spontaneous preference for fat in lean mice. Taken together these data bring the demonstration that a saturated high fat diet elicits an inflammatory response at the level of peripheral gustatory pathway and a LPS-induced low-grade endotoxemia alone does not explain the change in the preference for dietary lipids observed in DIO mice.

    更新日期:2018-11-29
  • Thermodynamic Investigation of Kissing-Loop Interactions
    Biochimie (IF 3.188) Pub Date : 2018-11-28
    Carolyn E. Carr, Luis A. Marky

    Kissing loop interactions (KLIs) are a common motif that is critical in retroviral dimerization, viroid replication, mRNA, and riboswitches. In addition, KLIs are currently used in a variety of biotechnology applications, such as in aptamer sensors, RNA scaffolds and to stabilize vaccines for therapeutics. Here we describe the thermodynamics of a basic intramolecular DNA capable of engaging in a KLI, consisting of two hairpins connected by a flexible linker. Each hairpin loop has a five-nucleotide complementary sequence theoretically capable of engaging in a KLI. On either side of each loop is two thymines which will not engage in kissing but are present to provide more flexibility and optimal KLI positioning. Our results suggest that the KLI occurs even at physiological salt levels, and that the KLI does not alter the thermodynamics and stability of the two stem structures. The KLI does not involve all five nucleotides, or at least each base-pair stack is not making full contact. Adding a second strand complementary to the bottom of the kissing complex removes flexibility and causes destabilization of the stems. The KLI of this less flexible complex is maintained but the TM is reduced, indicating an entopic penalty to its formation.

    更新日期:2018-11-28
  • Long Noncoding RNA NPCCAT1 promotes nasopharyngeal carcinoma progression via upregulating YY1
    Biochimie (IF 3.188) Pub Date : 2018-11-24
    Hongxia Su, Lei Liu, Yuan Zhang, Jia Wang, Yulin Zhao

    Long noncoding RNAs (lncRNAs) are frequently implicated in various cancers. However, the significances of lncRNAs in nasopharyngeal carcinoma (NPC) are largely unclear. In this study, we identified a novel lncRNA nasopharyngeal carcinoma copy number amplified transcript-1 (NPCCAT1), whose expression is increased in NPC tissues compared with nasopharyngeal normal tissues. Furthermore, we found the genomic copy number of NPCCAT1 is amplified in NPC, which contributes to the upregulation of NPCCAT1 in NPC. Functional experiments demonstrated that overexpression of NPCCAT1 promotes NPC cell growth and migration in vitro and NPC tumor growth in vivo. Knockdown of NPCCAT1 suppresses NPC cell grow and migration. Mechanistically, we found that NPCCAT1 directly binds YY1 mRNA 5'UTR, promotes YY1 mRNA translation, and upregulates YY1 protein level. Gain-of-function and loss-of-function assays revealed that YY1 promoted NPC cell proliferation and migration. Moreover, rescue assays showed that depletion of YY1 attenuated the roles of NPCCAT1 overexpression in promoting NPC cell growth and migration in vitro and NPC tumor growth in vivo. Overall, our study identified NPCCAT1 as an oncogenic lncRNA which promotes NPC progression via upregulating YY1, and suggested that lncRNA NPCCAT1 may be a promising therapeutic target for NPC.

    更新日期:2018-11-26
  • Biological applications of tethered bilayer lipid membranes
    Biochimie (IF 3.188) Pub Date : 2018-11-22
    Tadas Penkauskas, Giulio Preta

    Lipid membranes have an essential role in most physiological processes including cell protection, cell-to-cell communication and regulation of intracellular signaling. These multiple roles of biological membranes prompted the study and the development of artificial lipid membranes with the primary aim to reconstitute the natural functions in vitro and understand the interaction between all membrane components at the molecular level. Tethered bilayer lipid membranes (tBLMs) are emerging as the ideal experimental platform for functional and structural studies on membrane-associated proteins due to their peculiar properties such as their stability and fluidity of both leaflets in the phospholipid bilayer. tBLMs have been used in many studies, ranging from the analysis of membrane structure and function, studies of the membrane-protein and membrane-peptide interactions, as well as applications as biosensors and energy generating devices. This review describes all the uses of tBLMs as a tool to investigate biological functions, pointing out limitations of this methodology and future applications once optimization of the technique will be achieved.

    更新日期:2018-11-24
  • Properties of a recombinant GH49 family dextranase heterologously expressed in two recipient strains of Penicillium species
    Biochimie (IF 3.188) Pub Date : 2018-11-23
    Pavel V. Volkov, Alexander V. Gusakov, Ekaterina A. Rubtsova, Alexandra M. Rozhkova, Veronica Yu. Matys, Vitaly A. Nemashkalov, Arkady P. Sinitsyn

    The dexA gene encoding Penicillium funiculosum dextranase (GenBank accession MH581385) belonging to family 49 of glycoside hydrolases (GH49) was cloned and heterologously expressed in two recipient strains, P. canescens RN3-11-7 and P. verruculosum B1-537. Crude enzyme preparations with the recombinant dextranase content of 8–36% of the total secreted protein were obtained on the basis of new Penicillium strains. Both recombinant forms of the dextranase were isolated in a homogeneous state using chromatographic techniques. The purified enzymes displayed very similar properties, that is, pI 4.55, activity optima at pH 4.5–5.0 and 55–60 °C and a melting temperature of 60.7–60.9 °C. They were characterized by similar specific activities (1020–1340 U/mg) against dextrans with a mean molecular mass of 20, 70 and 500 kDa, as well as similar kinetic parameters in the hydrolysis of 70 kDa dextran (Km = 1.10–1.11 g/L, kcat = 640–680 s−1). However, the recombinant dextranases expressed in P. canescens and P. verruculosum had different molecular masses according to the data of SDS-PAGE (∼63 and ∼60 kDa, respectively); this was the result of different N-glycosylation patterns as MALDI-TOF mass spectrometry analysis showed. The main products of dextran hydrolysis at its initial phase were isomaltooligosaccharides, while after the prolonged time (24 h) the reaction system contained isomaltose and glucose as the major products and minor amounts of other oligosaccharides.

    更新日期:2018-11-24
  • Thermodynamics and Site Stoichiometry of DNA Binding by a Large Antiviral Hairpin Polyamide
    Biochimie (IF 3.188) Pub Date : 2018-11-24
    Yang Song, Jacquelyn Niederschulte, Kristin N. Bales, James K. Bashkin, Cynthia M. Dupureur

    PA1(dIm-PyPyβPyPyPy-γ-PyPyβPyPyPyPyβ-Ta) is a large (14-ring) hairpin polyamide that was designed to recognize the DNA sequence 5’-W2GW7-3’, where W is either A or T. As is common among the smaller 6-8-ring hairpin PAs, it binds its target recognition sequence with low nM affinity. However, in addition to its large size, it is distinct from these more extensively characterized in its high tolerance for mismatches and antiviral properties. In ongoing attempts to understand the basis for these distinctions, we conducted thermodynamics studies of PA1-DNA interactions. The temperature dependence of binding affinity was measured using TAMRA-labeled hairpin DNAs containing a single target sequence. PA1 binding to either an ATAT/TATA or an AAAA/TTTT pattern is consistently entropically driven. This is in contrast to the A/T pattern-dependent driving forces for DNA binding by netropsin, distamycin, and smaller hairpin polyamides. Analysis of the salt dependence of PA1-DNA binding reveals that within experimental error, there is no dependence on ionic strength, indicating that the polyelectrolyte effect does not contribute to PA1-DNA binding energetics. This is similar to that observed for smaller PAs. PA1-DNA recognition sequence binding stoichiometries were determined at both nM (fluorescence) and μM (circular dichroism) concentrations. With all sequences and under both conditions, multiple PA1 molecules bind the small DNA hairpin that contains only a single recognition sequence. Implications for these observations are discussed.

    更新日期:2018-11-24
  • Thermodynamic signature of indoloquinolines interacting with G-quadruplexes: impact of ligand side chain
    Biochimie (IF 3.188) Pub Date : 2018-11-24
    Andrea Funke, Klaus Weisz

    Binding of indoloquinolines with different aliphatic side chains to a parallel G-quadruplex derived from the MYC promoter sequence was characterized by optical and calorimetric measurements. ITC experiments performed at different temperatures enabled the determination of molar heat capacity changes upon quadruplex binding and a partitioning of the total binding free enthalpy into contributing terms with hydrophobic effects being major driving forces for all derivatives. Whereas affinities increase for indoloquinolines equipped with a long and positively charged side arm, the highest contribution of specific intermolecular interactions anticipated to impart enhanced specificity is found for a ligand with an uncharged ether aliphatic tail. Obtained thermodynamic signatures may considerably aid in the rational selection of ligand side chains for G-quadruplex binders with enhanced affinity or selectivity.

    更新日期:2018-11-24
  • Could glucagon-like peptide-1 be a potential biomarker of early-stage intestinal ischemia?
    Biochimie (IF 3.188) Pub Date : 2018-11-14
    Lorène J. Lebrun, Jacques Grober

    Intestinal ischemia, also called mesenteric ischemia, is a severe gastrointestinal and vascular medical emergency caused by a sudden decrease of blood flow through the mesenteric vessels. It generates hypoperfusion of intestinal tissues and can rapidly progress to intestinal wall infarction, systemic inflammation or even death if not treated in time. The mortality of this condition is still considerably high despite all the medical advances of the past few years. This is partially due to the difficulty of diagnosing early stage mesenteric ischemia. Indeed, a speedy and correct diagnosis is decisive for suitable medical care. However, early symptoms are unspecific and conventional clinical markers are neither specific nor sensitive enough. In the last few years, significant clinical and preclinical efforts have been made to find biomarkers which could predict gastrointestinal damage before it becomes irreversible. Here, the gut-derived hormone glucagon-like peptide-1 (GLP-1) is described as a potential early biomarker of this severe condition. Indeed, GLP-1 plasma levels rise rapidly in both mice and humans with intestinal ischemia. This discovery could counter the cruel lack of clinical biomarkers available to diagnose and therefore manage intestinal ischemia efficiently in the early stages. GLP-1 could thus become part of a panel of biomarkers for intestinal ischemia and could help to reduce the associated high mortality rates.

    更新日期:2018-11-14
  • Neotuberostemonine inhibits osteoclastogenesis via blockade of NF-κB pathway
    Biochimie (IF 3.188) Pub Date : 2018-11-13
    Jangmi Yun, Ki Yong Lee, Byoungduck Park

    Osteoporosis has been attributed to low bone mass arising from cellular communications between bone formation and bone resorption. Osteoclastogenesis is induced by M-CSF and RANKL in hematopoietic lineage cells. Once RANK/RANKL complex is formed, TRAF6 is recruited and triggers the activation of NF-κB pathway and the expression of osteoclast-related genes including NFATc1. Neotuberostemonine (NTS) is an active compound isolated from Stemona tuberosa Lour. Pharmacologically, NTS has been known to possess antitussive, anti-fibrotic and anti-inflammatory activities through regulation of macrophage. However, the influence of NTS to osteoclastogenesis has not been reported. The purpose of this study is to investigate whether NTS can modulate the osteoclastogenesis induced by RANKL or cancer cells. We found that NTS inhibits RANKL- or cancer cell-mediated osteoclastogenesis via blockade of TRAF6 and NF-κB activation. NTS also impairs the formation of F-actin ring structure, an important feature of osteoclast differentiation and function. These results indicate that NTS can be a preventive and therapeutic candidate for bone-related disease and that NTS provides insights underlying molecular mechanisms that influence osteoclastogenesis.

    更新日期:2018-11-13
  • Study of the metabolomic relationship between lung cancer and chronic obstructive pulmonary disease based on direct infusion mass spectrometry
    Biochimie (IF 3.188) Pub Date : 2018-11-13
    B. Callejón-Leblic, A. Pereira-Vega, E. Vazquez-Gandullo, J.L. Sánchez-Ramos, J.L. Gómez-Ariza, T. García-Barrera

    The high prevalence of lung cancer (LC) has triggered the search of biomarkers for early diagnosis of this disease. For this purpose the study of metabolic changes related to the development of lung cancer could provide interesting information about its early diagnosis. In this sense, chronic obstructive pulmonary disease (COPD), a disease associated with tumor development, is a comorbidity that increases the risk of onset and progression of lung neoplasia and has also to be considered in the study of pathology related to lung cancer. This work develop a metabolomic approach based on direct infusion mass spectrometry using a hybrid triple quadrupole-time of flight mass spectrometer (DI-ESI-QqQ-TOF-MS) in order to identify altered metabolites from serum of LC and COPD patients and evaluate its relationship and implication in the progression of LC. This methodology has been applied to 30 serum samples from LC, 30 healthy patients used as controls (HC) and 30 serum samples from COPD to found altered metabolites from both LC and COPD diseases. In addition, some metabolic differences and similarities were found in Pulmonary Emphysema and Chronic Bronchitis patients. On the other hand, altered metabolites were studied in different stages of LC (II, III and IV) to evaluate the perturbation of them throughout the progression of disease. The sample treatment consisted of the extraction of polar and non-polar metabolites from serum that was later infused into the mass spectrometer using an electrospray ionization source in positive and negative mode. Partial least squares discriminant analysis (PLS-DA) allowed a classification between LC, HC and COPD groups in all acquisition modes. A total of 35 altered and common metabolites between LC and COPD, including amino acids, fatty acids, lysophospholipids, phospholipids and triacylglycerides were identified, being alanine, aspartate and glutamate metabolism the most altered. Finally, ROC curves were applied to the dataset and metabolites with AUC value higher than 0.70 were considered as relevant in the progression of LC.

    更新日期:2018-11-13
  • Serotonin in retina
    Biochimie (IF 3.188) Pub Date : 2018-11-09
    Justine Masson

    The expression of serotonin (5-HT) in the retina was first reported in the sixties. The detection of vesicular monoamine transporter and serotonin receptors in several retinal cells confirm that 5-HT is playing a neuromodulatory role in this structure. Whereas signaling pathways activated by 5-HT receptor binding has been poorly investigated so far, numerous data demonstrated that 5-HT is involved in retinal physiology, retinal physiopathology and photoreceptor survival.

    更新日期:2018-11-09
  • A novel uORF-based regulatory mechanism controls translation of the human MDM2 and eIF2D mRNAs during stress
    Biochimie (IF 3.188) Pub Date : 2018-11-09
    Kseniya A. Akulich, Pavel G. Sinitcyn, Desislava S. Makeeva, Dmitry E. Andreev, Ilya M. Terenin, Aleksandra S. Anisimova, Ivan N. Shatsky, Sergey E. Dmitriev
    更新日期:2018-11-09
  • Role of Adenomatous Polyposis Coli (APC) gene mutations in the pathogenesis of colorectal cancer; current status and perspectives
    Biochimie (IF 3.188) Pub Date : 2018-11-08
    Amirsaeed Sabeti Aghabozorgi, Amirhossein Bahreyni, Atena Soleimani, Afsane Bahrami, Majid Khazaei, Gordon A. Ferns, Amir Avan, Seyed Mahdi Hassanian

    Colorectal cancer (CRC) is one of the most common forms of solid tumors in the world with high rates of mortality and morbidity. Most cases of CRCs are initiated by inactivating mutations in a tumor suppressor gene, adenomatous polyposis coli (APC), leading to constitutive activation of the Wnt signaling pathway. This review summarizes the roles of somatic and germline mutations of the APC gene in hereditary as well as sporadic forms of CRC. We also discuss the diagnostic and prognostic value of the APC gene in the pathogenesis of CRC for a better understanding of CRC disease.

    更新日期:2018-11-08
  • A secondary structure within a human piRNA modulates its functionality
    Biochimie (IF 3.188) Pub Date : 2018-11-08
    Sumirtha Balaratnam, Madara Hettiarachchilage, Nicole West, Helen Piontkivska, Soumitra Basu
    更新日期:2018-11-08
  • Virus-like nanoparticles as a novel delivery tool in gene therapy
    Biochimie (IF 3.188) Pub Date : 2018-11-05
    Jaison Jeevanandam, Kaushik Pal, Michael K. Danquah
    更新日期:2018-11-05
  • Mo-CBP3-PepI, Mo-CBP3-PepII, and Mo-CBP3-PepIII are synthetic antimicrobial peptides active against human pathogens by stimulating ROS generation and increasing plasma membrane permeability
    Biochimie (IF 3.188) Pub Date : 2018-10-31
    Jose T.A. Oliveira, Pedro F.N. Souza, Ilka M. Vasconcelos, Lucas P. Dias, Thiago F. Martins, Mauricio F. Van Tilburg, Maria I.F. Guedes, Daniele O.B. Sousa
    更新日期:2018-11-02
  • Cytotoxic action of acetate on tumor cells of thymic origin: Role of MCT-1, pH homeostasis and altered cell survival regulation
    Biochimie (IF 3.188) Pub Date : 2018-11-01
    Shrish Kumar Pandey, Saveg Yadav, Yugal Goel, Sukh Mahendra Singh

    Neoplastic cells display altered biosynthetic and bioenergetic machinery to support cell survival. Therefore, cancer cells optimally utilize all available fuel resources to pump their highly upregulated metabolic pathways. While glucose is the main carbon source, transformed cells also utilize other molecules, which can be utilized in metabolic pathways, designated as alternative fuels. Acetate is one of such alternative metabolic fuels, which is mainly consumed in carbohydrate and lipid metabolism. However, studies demonstrate the contradictory effects of acetate on tumor cell survival. Moreover, the mechanisms of its antitumor actions remain poorly understood. Further, the spectrum of acetate susceptible tumor targets needs to be characterized in order to optimize the use of acetate in maneuvering tumor progression as a therapeutic strategy. As the effect of acetate on survival properties of the tumor cells of thymic origin is not worked out, in the present study the effect of acetate was investigated against tumor cells derived from a murine thymoma designated as Dalton’s Lymphoma (DL). Acetate treatment of tumor cells inhibited tumor cell survival accompanied by induction of apoptotic cell death, associated with modulated expression of cell survival regulatory HIF1α, ROS, p53, Caspase 3, Bax and HSP70 along with the elevated level of cytosolic cytochrome c. Acetate treatment also modulated the expression of pH regulators MCT-1 and V-ATPase accompanied by altered pH homeostasis. Expression of MDR and lipid metabolism regulatory molecules was also inhibited in tumor cells upon acetate exposure. Further, pre-exposure of tumor cells to α-CHC (α-cyano-4-hydroxycinnamate), an inhibitor of MCT-1, partially abrogated the cytotoxic action of acetate. These findings shed a new light regarding the effect and mechanisms of the exogenous acetate on the biology of tumor cells of thymic origin.

    更新日期:2018-11-02
  • Silencing of LncRNA Steroid Receptor RNA Activator attenuates polycystic ovary syndrome in Mice
    Biochimie (IF 3.188) Pub Date : 2018-11-01
    Yan Li, Wanqiu Zhao, Haixu Wang, Chen Chen, Dongmei Zhou, Shengnan Li, Xiaohong Zhang, Haibo Zhao, Dangxia Zhou, Biliang Chen

    Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and has a prevalence of 1 in 15 women worldwide. This study aims to investigate the role of lncRNA SRA in the pathological processes of polycystic ovary syndrome (PCOS). Methods Twenty five-day old female C57BL/6 mice received subcutaneous injection of 60 mg/kg dehydroepiandrosterone for 20 days to induce PCOS. Lentivirus containing lncRNA SRA-specific shRNA was subcapsularly injected into the ovaries of PCOS mice. Granulosa cell was primary cultured to explore the mechanism of DHEA-induced inflammatory responses. H&E staining was used to examine the histological changes of ovaries. ELISA was used to assess serum insulin level and proinflammatory cytokines and angiogenetic factors contents in ovary tissue. The expression levels of LncRNA SRA and proteins involved in the NF-κB signaling pathway were detected through Quantitative real-time PCR and Western blot. The nuclear translocation of NF-κB was observed by immunofluorescence and the activity of NF-κB-DNA binding was detected using EMSA. Results Silencing of lncRNA SRA changed insulin release, attenuated ovary injury and reduced the production of angiogenetic factors in the PCOS mice. In addition, shRNA targeting lncRNA SRA inhibited DHEA-induced pro-inflammatory cytokines production and NF-κB nuclear translocation in the ovary of PCOS mice and primary granulosa cells. Conclusion Silencing of lncRNA Steroid Receptor RNA Activator (SRA) attenuates polycystic ovary syndrome (PCOS) in mice. LncRNA SRA plays important roles in the development of PCOS.

    更新日期:2018-11-02
  • Autoantibody against arrestin-1 as a potential biomarker of renal cell carcinoma
    Biochimie (IF 3.188) Pub Date : 2018-10-30
    Alexey V. Baldin, Alena N. Grishina, Dmitry O. Korolev, Ekaterina B. Kuznetsova, Marina O. Golovastova, Alexey S. Kalpinskiy, Boris Y. Alekseev, Andrey D. Kaprin, Dmitry V. Zinchenko, Lyudmila V. Savvateeva, Vladimir A. Varshavsky, Evgeni Yu Zernii, Andrey Z. Vinarov, Alexandr V. Bazhin, Pavel P. Philippov, Andrey A. Zamyatnin

    Renal cell carcinoma (RCC) is the second-most common uronephrological cancer. In the absence of specific symptoms, early diagnosis of RCC is challenging. Monitoring of the aberrant expression of tumour-associated antigens (TAAs) and related autoantibody response is considered as a novel approach of RCC diagnostics. The aim of this study was to examine the aberrant expression of arrestin-1 in renal tumours, to investigate the possible epigenetic mechanism underlying arrestin-1 expression, and to assess the frequency of anti-arrestin-1 autoantibody response. Immunohistochemistry was used to assess the presence of arrestin-1 in primary tumours and metastases of 39 patients with RCC and renal oncocytoma. Bisulfite sequencing was employed to analyse the methylation status of the promoter of the SAG gene encoding arrestin-1. Western blot analysis was performed to detect autoantibodies against arrestin-1 in serum samples of 36 RCC and oncocytoma patients. Arrestin-1 was found to be expressed in RCC (58.7% of cases) and renal oncocytoma (90% of cases) cells, while being absent in healthy kidney. The expression of arrestin-1 in RCC metastases was more prominent than in primary tumours. Hypomethylation of the SAG gene promoter is unlikely to be the mechanism for the aberrant expression of arrestin-1. Autoantibodies against arrestin-1 were detected in sera of 75% of RCC patients. Taken together, our findings suggest employment of autoantibody against arrestin-1 as biomarker of RCC.

    更新日期:2018-10-31
  • Thermal Denaturation Profile: A Straightforward Signature to Characterize Parallel G-quadruplexes
    Biochimie (IF 3.188) Pub Date : 2018-10-31
    Yingying Zhang, Jielin Chen, Huangxian Ju, Jun Zhou
    更新日期:2018-10-31
  • Subatomic structure of hyper-sweet thaumatin D21N mutant reveals the importance of flexible conformations for enhanced sweetness
    Biochimie (IF 3.188) Pub Date : 2018-10-31
    Tetsuya Masuda, Kyohei Okubo, Kazuki Murata, Bunzo Mikami, Michihiro Sugahara, Mamoru Suzuki, Piero Andrea Temussi, Fumito Tani
    更新日期:2018-10-31
  • 3D structure of the natural tetrameric form of human butyrylcholinesterase as revealed by cryoEM, SAXS and MD
    Biochimie (IF 3.188) Pub Date : 2018-10-29
    Konstantin M. Boyko, Timur N. Baymukhametov, Yury M. Chesnokov, Michael Hons, Sofya V. Lushchekina, Petr V. Konarev, Alexey V. Lipkin, Alexandre L. Vasiliev, Patrick Masson, Vladimir O. Popov, Michail V. Kovalchuk
    更新日期:2018-10-30
  • The 5-HT1A receptor: signaling to behavior
    Biochimie (IF 3.188) Pub Date : 2018-10-25
    Paul R. Albert, Faranak Vahid-Ansari
    更新日期:2018-10-26
  • Secretome proteins regulate comparative osteogenic and adipogenic potential in bone marrow and dental stem cells
    Biochimie (IF 3.188) Pub Date : 2018-10-24
    Ajay Kumar, Vinod Kumar, Vidya Rattan, Vivekananda Jha, Shalmoli Bhattacharyya
    更新日期:2018-10-25
  • Bacterial ribosome heterogeneity: Changes in ribosomal protein composition during transition into stationary growth phase
    Biochimie (IF 3.188) Pub Date : 2018-10-23
    Silva Lilleorg, Kaspar Reier, Arto Pulk, Aivar Liiv, Triin Tammsalu, Lauri Peil, Jamie.H.D. Cate, Jaanus Remme
    更新日期:2018-10-23
  • Epigenetics in the early divergent eukaryotic Giardia duodenalis: an update
    Biochimie (IF 3.188) Pub Date : 2018-10-19
    Francisco Alejandro Lagunas-Rangel, Rosa María Bermúdez-Cruz

    Giardia duodenalis is a flagellated unicellular eukaryotic microorganism that usually parasitizes the small intestine of humans and many other vertebrates causing diarrheal disease throughout the world. Notably, Giardia despite minimization of most cellular systems shows different strategies to adapt to environmental conditions, evade the immune system and resist exposure to antimicrobial agents. Over the past years, epigenetic regulation of gene expression has been shown to have a relevant role in the parasite’s biology. Interestingly, analysis of the Giardia genome revealed the presence of enzymes responsible for post-translational modification in histones, therefore suggesting that epigenetic mechanisms may regulate gene expression in this parasite. Thus, the purpose of this review is to summarize how epigenetic mechanisms play relevant roles in the pathogenicity of Giardia, with a particular emphasis on the molecular mechanisms associated with parasite differentiation, antigenic variation and antimicrobial resistance.

    更新日期:2018-10-22
  • High altitude mediated skeletal muscle atrophy: Protective role of curcumin
    Biochimie (IF 3.188) Pub Date : 2018-10-19
    Pooja Chaudhary, Yogendra Kumar Sharma, Shivani Sharma, Som Nath Singh, Geetha Suryakumar

    Chronic hypobaric hypoxia induced muscle atrophy results in decreased physical performance at high altitude. Curcumin has been shown to have muscle sparing effects under cachectic conditions. However, the protective effects of curcumin under chronic hypobaric hypoxia have not been studied till now. Therefore, the present study aims at evaluating the effects of curcumin administration on muscle atrophy under chronic hypobaric hypoxia. Male Sprague Dawley rats were divided into four groups: Control (C)-normoxia exposed, Control Treated (CT)-normoxia exposed and administered with curcumin at a dose of 100 mg/kg body weight for 14 days, Hypoxia (H)-exposed to hypobaric hypoxia for 14 days and Hypoxia Treated (HT)-exposed to hypobaric hypoxia and administered with curcumin for 14 days. Oxidative stress, muscle protein degradation, proteolytic pathways, myosin heavy chain (MHC), CPK activity and muscle histology were performed in gastrocnemius muscle samples of the exposed rats. In addition, fatigue time on treadmill running was also evaluated to observe the effects of curcumin administration on physical performance of the rats. As previously shown, hypobaric hypoxia increased muscle protein degradation via upregulated calpain and ubiquitin-proteolytic pathways. An enhanced oxidative stress has been linked to upregulation of these pathways under hypoxic conditions. Curcumin administration resulted in reduced oxidative stress as well as reduced activity of the proteolytic pathways in HT group as compared to H group thereby resulting in reduced muscle protein degradation under hypobaric hypoxia. Histology of rat muscle revealed an increased number of muscle fibres in HT as compared to H group. Thus, increased number of muscle fibres and decreased muscle proteolysis following curcumin administration, lead to enhanced muscle mass under hypobaric hypoxia resulting in improved physical performance of the rats.

    更新日期:2018-10-22
  • LncRNA ANRIL promotes NLRP3 inflammasome activation in uric acid nephropathy through miR-122-5p/BRCC3 axis
    Biochimie (IF 3.188) Pub Date : 2018-10-19
    Jiacai Hu, Hao Wu, Daochun Wang, Zhijie Yang, Junjun Dong

    This study is designed to explore the mechanism by which long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) plays a pathogenic role in uric acid nephropathy (UAN). The expressions of ANRIL, miR-122-5p, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and NOD-like receptor protein 3 (NLRP3) were determined in UAN patients and uric acid-treated HK-2 cells by qRT-PCR. Protein levels of BRCC3 and NLRP3 were examined by western blot. The levels of inflammatory cytokines were quantified by ELISA. CCK-8 assay was used to assess cell viability. Apoptosis was detected by Annexin V-FITC/PI double-labeled flow cytometry and TUNEL assay. The interaction between ANRIL, miR-122-5p and BRCC3 were studied using luciferase reporter assay. The role of ANRIL in renal injury was evaluated in experimental rats. ANRIL and BRCC3 were highly expressed while miR-122-5p was down-regulated in serum of UAN patients and uric acid-treated tubular epithelial cells. Luciferase reporter assay and in vitro rescue experiment confirmed that ANRIL promoted NLRP3 inflammasome activation by up-regulating BRCC3 expression via sponging miR-122-5p. Furthermore, in vivo experiment validated that knockdown of ANRIL alleviated renal injury of UAN rats. ANRIL exerted pathogenic effect in UAN to promote NLRP3 inflammasome activation via miR-122-5p/BRCC3 axis.

    更新日期:2018-10-22
  • Neuroprotective effects of Tat-ATOX1 protein against MPP+-induced SH-SY5Y cell deaths and in MPTP-induced mouse model of Parkinson’s disease
    Biochimie (IF 3.188) Pub Date : 2018-10-21
    Won Sik Eum, Min Jea Shin, Chi Hern Lee, Hyeon Ji Yeo, Eun Ji Yeo, Yeon Joo Choi, Hyun Jung Kwon, Duk-Soo Kim, Oh Shin Kwon, Keun Wook Lee, Kyu Hyung Han, Jinseu Park, Dae Won Kim, Soo Young Choi

    Parkinson’s disease (PD), a neurodegenerative disorder, is characterized by a loss of dopaminergic neurons in the substantia nigra (SN) of the brain and it is well known that the pathogenesis of PD is related to a number of risk factors including oxidative stress. Antioxidant 1 (ATOX1) protein plays a crucial role in various diseases as an antioxidant and chaperone. In this study, we determined whether Tat-ATOX1 could protect against 1-methyl-4-phenylpyridinium ion (MPP+)-induced SH-SY5Y cell death and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of PD. In the MPP+ exposed SH-SY5Y cells, Tat-ATOX1 markedly inhibited cell death and toxicities. In addition, Tat-ATOX1 markedly suppressed the activation of Akt and mitogen activated protein kinases (MAPKs) as well as cleavage of caspase-3 and Bax expression levels. In a MPTP-induced animal model, Tat-ATOX1 transduced into brain and protected dopaminergic neuronal cell loss. Taken together, Tat-ATOX1 inhibits dopaminergic neuronal death through the suppression of MAPKs and apoptotic signal pathways. Thus, Tat-ATOX1 represents a potential therapeutic protein drug candidate for PD.

    更新日期:2018-10-22
  • Ferrochelatase activity of plant frataxin
    Biochimie (IF 3.188) Pub Date : 2018-10-18
    Alejandro M. Armas, Manuel Balparda, Agustina Terenzi, Maria V. Busi, Maria A. Pagani, Diego F. Gomez-Casati

    Frataxin plays a key role in cellular iron homeostasis of different organisms. It is engaged in several activities at the Fe-S cluster assembly machinery and it is also involved in heme biosynthesis. In plants, two genes encoding ferrochelatases (FC1 and FC2) catalyze the incorporation of iron into protoporphyrin IX in the last stage of heme synthesis in chloroplasts. Despite ferrochelatases are absent from other cell compartments, a remaining ferrochelatase activity has been observed in plant mitochondria. Here we analyze the possibility that frataxin acts as the iron donor to protoporphyrin IX for the synthesis of heme groups in plant mitochondria. Our findings show that frataxin catalyzes the formation of heme in vitro when it is incubated with iron and protoporphyrin IX. When frataxin is combined with AtNFS1 and AtISD11 the ferrochelatse activity is increased. These results suggest that frataxin could be the iron donor in the final step of heme synthesis in plant mitochondria, and constitutes an important advance in the elucidation of the mechanisms of heme synthesis in plants.

    更新日期:2018-10-19
  • Influence of Passage Number on the Impact of the Secretome of Adipose Tissue Stem Cells on Neural Survival, Neurodifferentiation and Axonal Growth
    Biochimie (IF 3.188) Pub Date : 2018-10-17
    Sofia C. Serra, João C. Costa, Rita C. Assunção-Silva, Fábio G. Teixeira, Nuno A. Silva, Sandro I. Anjo, Bruno Manadas, Jeffrey Gimble, Leo A. Behie, António J. Salgado

    Mesenchymal stem cells (MSCs), and within them adipose tissue derived stem cells (ASCs), have been shown to have therapeutic effects on central nervous system (CNS) cell populations. Such effects have been mostly attributed to soluble factors, as well as vesicles, present in their secretome. Yet, little is known about the impact that MSC passaging might have in the secretion therapeutic profile. Our aim was to show how human ASCs (hASCs) passage number influences the effect of their secretome in neuronal survival, differentiation and axonal growth. For this purpose, post-natal rat hippocampal primary cultures, human neural progenitor cell (hNPCs) cultures and dorsal root ganglia (DRGs) explants were incubated with secretome, collected as conditioned media (CMs), obtained from hASCs in P3, P6, P9 and P12. Results showed no differences when comparing percentages of MAP-2 positive cells (a mature neuronal marker) in neuronal cultures or of hNPCs that differentiated, after incubation with hASCs secretome from different passages. The same was observed regarding DRG neurite outgrowth. In order to characterize the secretomes obtained from different passages, a proteomic analysis was performed, revealing that its composition did not vary significantly with passage number P3 to P12. Results allowed us to identify several key proteins, such as pigment epithelium derived factor (PEDF), DJ-1, interleucin-6 (IL-6) and galectin, all of which have already proven to play neuroprotective and neurodifferentiating roles. Proteins that promote neurite outgrowth were also found present, such as semaphorin 7A and glypican-1. We conclude that cellular passaging does not influence significantly hASC’s secretome properties especially their ability to support post-natal neuronal survival, induce neurodifferentiation and promote axonal growth.

    更新日期:2018-10-18
  • Self-association and folding in membrane determine the mode of action of peptides from the lytic segment of sticholysins
    Biochimie (IF 3.188) Pub Date : 2018-10-13
    Uris Ros, Gustavo P.B. Carretero, Joana Paulino, Edson Crusca, Fabiola Pazos, Eduardo M. Cilli, Maria E. Lanio, Shirley Schreier, Carlos Alvarez
    更新日期:2018-10-14
  • Stabilization of miRNAs in esophageal cancer contributes to radioresistance and limits efficacy of therapy
    Biochimie (IF 3.188) Pub Date : 2018-10-13
    Akshay Malhotra, Uttam Sharma, Shyamly Puhan, Naga Chandra Bandari, Anjali Kharab, P.P Arifa, Lovlesh Thakur, Hridayesh Prakash, Karen M. Vasquez, Aklank Jain

    The five-year survival rate of esophageal cancer patients is less than 20%. This may be due to increased resistance (acquired or intrinsic) of tumor cells to chemo/radiotherapies, often caused by aberrant cell cycle, deregulated apoptosis, increases in growth factor signaling pathways, and/or changes in the proteome network. In addition, deregulation in non-coding RNA-mediated signaling pathways may contribute to resistance to therapies. At the molecular level, these resistance factors have now been linked to various microRNA (miRNAs), which have recently been shown to control cell development, differentiation and neoplasia. The increased stability and dysregulated expression of miRNAs have been associated with increased resistance to various therapies in several cancers, including esophageal cancer. Therefore, miRNAs represent the next generation of molecules with tremendous potential as biomarkers and therapeutic targets. Yet, a detailed studies on miRNA-based therapeutic intervention is still in its infancy. Hence, in this review, we have summarized the current status of microRNAs in dictating the resistance/sensitivity of tumor cells against chemotherapy and radiotherapy. In addition, we have discussed various strategies to increase radiosensitivity, including targeted therapy, and the use of miRNAs as radiosensitive/radioresistance biomarkers for esophageal cancer in the clinical setting.

    更新日期:2018-10-14
  • Activation of catalase via co-administration of aspirin and pioglitazone: Experimental and MLSD simulation approaches
    Biochimie (IF 3.188) Pub Date : 2018-10-14
    Yunes Panahi, Reza Yekta, Gholamreza Dehghan, Samaneh Rashtbari, Nematollah Jonaidi Jafari, Ali A. Moosavi-Movahedi

    Aspirin (ASP) and pioglitazone (PGL) are the most common drugs that are widely used by diabetic patients to control the blood sugar and hinder cardiovascular diseases. The interaction between PGL and ASP is one of the important medical issues to clarify the safety of co-administration of these drugs. In the present study, the effect of co-administered ASP with PGL was investigated on the structure and catalytic function of catalase as a potential target in the liver. Based on our data, co-administration of ASP-PGL significantly enhanced the catalase activity in comparison with PGL alone. However, ASP does not have any effects on the catalytic function of catalase. Moreover, the dialysis measurement and CD spectroscopy study revealed that binding of ASP to catalase could increase the stability of catalase-PGL complex. Based on the obtained data, it is shown that the binding of ASP to catalase led to increase the affinity of catalase to PGL. Binding analysis showed that the association constant of catalase-PGL was reduced considerably in the presence of ASP from 12.19 ±0. 1×106 M-1 to 6.4 ±0. 2×106 M-1 at 298K. Multiple ligands simultaneous docking (MLSD) also confirmed an increase in the binding affinity of PGL to catalase.

    更新日期:2018-10-14
  • Fragmentation of Escherichia coli mRNA by MazF and MqsR
    Biochimie (IF 3.188) Pub Date : 2018-10-10
    Toomas Mets, Sergo Kasvandik, Merilin Saarma, Ülo Maiväli, Tanel Tenson, Niilo Kaldalu

    MazEF and MqsRA are toxin-antitoxin systems, where the toxins MazF and MqsR sequence-specifically cleave single-stranded RNA, thereby shutting down protein synthesis and cell growth. However, it has been proposed that MazF functions in a highly specific pathway, where it truncates the 5’ ends of a set of E. coli transcripts (the MazF regulon), which are then translated under stress conditions by specialized ribosomes. We mapped the cleavage sites of MazF and MqsR throughout the E. coli transcriptome. Our results show that both toxins cleave mRNA independently of the recognition site position and MazF freely cleaves transcripts of the proposed MazF regulon within coding sequences. Proteome analysis indicated that MazF expression leads to overall inhibition of protein synthesis and the putative MazF regulon proteins are not selectively synthesized in response to the toxin. Our results support a simpler role for endoribonuclease TA systems as indifferent destroyers of unstructured RNA.

    更新日期:2018-10-11
  • Lysines residing in putative small ubiquitin-like modifier (SUMO) motifs regulate fate and function of 37 KDa Laminin Receptor
    Biochimie (IF 3.188) Pub Date : 2018-10-10
    Charles Samuel Umbaugh, Marxa L. Figueiredo

    There is a putative precursor to a mature receptor relationship between 37 Laminin Receptor (LR) and 67 LR. As such, the pair are frequently referred to as a single entity, the 37/67 kDa Laminin Receptor (37/67 LR) and 67 LR was identified as a laminin binding entity. 37/67 LR has been of clinical interest for many years, as 37/67 LR is a prognostic indicator for many cancers including breast, lung, colon, and prostate. However, the genesis of 67LR is controversial, and confounded by its stability under SDS-PAGE conditions, a lack of splice variants, and the existence of post-translational modifications that cannot account for the mass discrepancy between 37 and 67 LR. In the present work, we mutated potential SUMO motif sites (Lysine residues) in 37 LR and generated a series of 37 LR-expressing plasmids with a C-terminal histidine tag. We report an inability to detect 67 LR formation, suggesting that SUMOylation does not appear to directly occur at the lysine residues proposed. However, the work revealed that these lysine mutations still appear to be important and can impact the fate and function for 37 LR, for example impairing half-life and steady state pre-mRNA levels. These results suggest that the Lys residues within putative SUMO motifs in 37 LR may indirectly coordinate with SUMO pathways.

    更新日期:2018-10-10
  • α-Lipoic acid and Amlodipine/Perindopril combination potentiate the therapeutic effect of mesenchymal stem cells on Isoproterenol induced cardiac injury in rats
    Biochimie (IF 3.188) Pub Date : 2018-10-08
    Abeer I. Abd El-Fattah, M.S. Zaghloul, N.A. Eltablawy, L.A. Rashed

    Cardiac injury is a dangerous disease and become a greater issue in the forthcoming decades. The ultimate goal is to prevent the progression of heart failure and apoptotic processes. Cardiac tissue may regenerate itself but to certain extent depending on the number of resident stem cells that is limited. Thus, research had been focused on bone marrow derived stem cells (BM-MSCs) as a promising therapy in different types of tissues, including the heart. This study is designed not only to assess the therapeutic effect of BM-MSCs but also to improve their therapeutic effect in combination with antioxidant α-lipoic acid (ALA) and antihypertensive therapeutic drug form (AP) against isoproterenol-induced cardiac injury and compared with that of BM-MSCs alone. Cardiac injury was induced in 70 male rats by Isoproterenol (ISO was injected s.c. for four consecutive days). Experimental animals were divided into six ISO-treated groups beside a control non treated one. The six ISO-treated groups were divided into: ISO group, ISO+BM-MSCs group, ISO+ALA group, ISO+AP group, ISO+ALA+AP group and ISO+ALA+AP+BM-MSCs group, the last five groups were treated with the examined materials after one week of ISO injection. Isoproterenol significantly increased serum CK-MB, LDH activities, Troponin1 and TNF-α. Oxidative stress is evidenced by the increased MDA, NO and Caspase-3 activity associated with significant reduction of GSH content and SOD activity in cardiac tissue. Furthermore, mRNA expression of NFκB and iNOS were significantly up regulated and eNOS mRNA expression was down regulated. Administration of BM-MSCs, ALA and AP alone significantly mitigated the induced cardiac injury. Concomitant administration of ALA and AP after BM-MSCs induced a more pronounced improving effect on cardiac functions. In conclusion, the concomitant administration of ALA and AP after BM-MSCs infusion increases the cellular antioxidant levels of cardiac tissue that improves the repairing function of BM-MSCs.

    更新日期:2018-10-08
  • MiR-650 regulates the proliferation, migration and invasion of human oral cancer by targeting Growth factor independent 1 (Gfi1)
    Biochimie (IF 3.188) Pub Date : 2018-10-06
    Sun Ningning, Sun Libo, Wu Chuanbin, Sun Haijiang, Zhou Qing

    Oral cancer being one of the lethal cancers is generally detected at advanced stages and causes significant mortality world over. The unavailability of the reliable biomarkers and therapeutic targets/agents forms a bottleneck in the treatment of oral cancer. MicroRNAs are considered of immense therapeutic potential for the treatment of cancer. Consistently, in this study the role and therapeutic potential of miR-650 was explored in oral cancer. The analysis of miR-650 expression by qRT-PCR revealed significant (p < 0.05) upregulation of miR-650 in oral cancer cell lines. Cell cycle analysis by flow cytometery revealed that suppression of miR-650 significantly (p < 0.05) inhibits the proliferation of the SCC-25 cells by prompting Sub-G1 cell cycle arrest. Further, miR-650 suppression also inhibited the migration and invasion of the SCC-25 oral cancer cells as revealed by transwell assays. TargetScan analysis showed that miR-650 targets Growth factor independent 1 (Gfi1). Moreover, the results of western blot analysis showed that miR-650 suppression inhibits the expression of Gfi1. Interestingly, suppression of Gfi1 exhibited similar effects on cell proliferation, migration and invasion of the oral cancer cells as that of miR-650 suppression. Nonetheless, miR-650 promoted the proliferation, migration and invasion of the SCC-25 cells by upregulating the expression of Gfi1. Moreover, overexpression of miR-650 could not rescue the effects of Gfi1 silencing on SCC-25 oral cancer cells. Conversely, overexpression of Gfi1 could rescue the effects of miR-650 inhibition on SCC-25 cell proliferation, migration and invasion. Additionally, miR-650 suppression could also inhibit the xenografted tumor growth in vivo by inhibiting the expression of Gfi1. Taken together, miR-650 may prove to be an important therapeutic target for the management of oral cancers.

    更新日期:2018-10-06
  • Chronic whole-body heat treatment relieves atherosclerotic lesions, cardiovascular and metabolic abnormalities, and enhances survival time restoring the anti-inflammatory and anti-senescent heat shock response in mice
    Biochimie (IF 3.188) Pub Date : 2018-09-28
    Maciel Alencar Bruxel, Angela Maria Vicente Tavares, Luiz Domingues Zavarize Neto, Victor de Souza Borges, Helena Trevisan Schroeder, Patricia Martins Bock, Maria Inês Lavina Rodrigues, Adriane Belló-Klein, Paulo Ivo Homem de Bittencourt
    更新日期:2018-09-29
  • Pro-inflammatory effects of extracellular Hsp70 and cigarette smoke in primary airway epithelial cells from COPD patients
    Biochimie (IF 3.188) Pub Date : 2018-09-27
    Andrea Hulina-Tomašković, Irene H. Heijink, Marnix R. Jonker, Anita Somborac-Bačura, Marija Grdić Rajković, Lada Rumora

    Extracellular Hsp70 (eHsp70) can activate immune cells via Toll-like receptors (TLR) 2 and 4, and induce cytokine synthesis. The aim of this study was to explore inflammation-associated effects of eHsp70 alone and in combination with cigarette smoke extract (CSE) in primary bronchial epithelial cells. We assessed IL-6 and IL-8 concentrations, TLR2, TLR4 and Hsp70 mRNA expressions, and mitogen-activated protein kinases (MAPKs) activation induced by recombinant human (rh) Hsp70, CSE or their combinations in normal human bronchial epithelial cells (NHBE) obtained commercially, and primary bronchial epithelial cells isolated from non-COPD lung donors (PBEC) or COPD patients (PBEC COPD). Baseline levels of IL-6 and IL-8 were significantly higher in PBEC COPD than in non-COPD PBECs. Upon rhHsp70 stimulation, IL-6 and IL-8 were significantly increased, with the strongest response in COPD-derived PBECs. CSE alone elevated cytokine secretion in all examined cells. rhHsp70 and CSE had antagonistic interactions on IL-8 release in PBECs from COPD patients, while the addition of rhHsp70 further increased CSE-induced IL-6 secretion in NHBE cells. rhHsp70 and CSE alone decreased TLR2 and TLR4 mRNA expression in COPD-derived PBECs. In non-COPD PBECs, combined treatments decreased only TLR2 mRNA expression. Hsp70 mRNA expression, as indicator of intracellular Hsp70, which may have anti-inflammatory effects, was reduced in COPD-derived cells upon exposure to CSE and rhHsp70 alone, but not with their combinations. Contrary to this, in PBECs from lung donors only combined treatments supressed Hsp70 gene expression. CSE activated JNK and p38 MAPKs, while rhHsp70 increased activation of c-Jun kinase in NHBE cells. Collectively, both eHsp70 and CSE induce pro-inflammatory responses in PBECs from non-COPD as well as COPD donors, but in combination antagonistic effects were observed in COPD-derived cells. These effects may be related to the regulation of TLR2/4 and might lead to modulation of inflammation with possible deleterious consequences for COPD patients.

    更新日期:2018-09-27
  • Nucleic acid aptamers in diagnosis of colorectal cancer
    Biochimie (IF 3.188) Pub Date : 2018-09-19
    Yaghoub Ahmadyousefi, Sara Malih, Younes Mirzaee, Massoud Saidijam
    更新日期:2018-09-20
  • Thermodynamics of the fourU RNA thermal switch derived from molecular dynamics simulations and spectroscopic techniques
    Biochimie (IF 3.188) Pub Date : 2018-09-19
    Filip Leonarski, Maciej Jasiński, Joanna Trylska
    更新日期:2018-09-20
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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