World Journal Of Biological Chemistry[JOURNAL]
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200 papers
New findings showing how DNA methylation influences diseases.
Sallustio F, Gesualdo L, Gallone A
World J Biol Chem · 2019 Jan · PMID 30622680 · Full text
In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest...
In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells. Major differences have been found between differentiated cells and stem cells. Methylation influences various pathologies, and it is very important to improve the understanding of the pathogenic mechanisms. Epigenetic modifications may take place throughout life and have been related to cancer, brain aging, memory disturbances, changes in synaptic plasticity, and neurodegenerative diseases, such as Parkinson's disease and Huntington's disease. DNA methylation also has a very important role in tumor biology. Many oncogenes are activated by mutations in carcinogenesis. However, many genes with tumor-suppressor functions are "silenced" by the methylation of CpG sites in some of their regions. Moreover, the role of epigenetic alterations has been demonstrated in neurological diseases. In neuronal precursors, many genes associated with development and differentiation are silenced by CpG methylation. In addition, recent studies show that DNA methylation can also influence diseases that do not appear to be related to the environment, such as IgA nephropathy, thus affecting the expression of some genes involved in the T-cell receptor signaling. In conclusion, DNA methylation provides a whole series of fundamental information for the cell to regulate gene expression, including how and when the genes are read, and it does not depend on the DNA sequence.
Arrestin-mediated signaling: Is there a controversy?
Gurevich VV, Gurevich EV
World J Biol Chem · 2018 Dec · PMID 30595812 · Full text
The activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors (GPCRs) arrestins, as opposed...
The activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors (GPCRs) arrestins, as opposed to conventional GPCR signaling G proteins. Several recent studies using HEK293 cells where all G proteins were genetically ablated or inactivated, or both non-visual arrestins were knocked out, demonstrated that ERK1/2 phosphorylation requires G protein activity, but does not necessarily require the presence of non-visual arrestins. This appears to contradict the prevailing paradigm. Here we discuss these results along with the recent data on gene edited cells and arrestin-mediated signaling. We suggest that there is no real controversy. G proteins might be involved in the activation of the upstream-most MAP3Ks, although most MAP3K activation is independent of heterotrimeric G proteins, being initiated by receptor tyrosine kinases and/or integrins. As far as MAP kinases are concerned, the best-established role of arrestins is scaffolding of the three-tiered cascades (MAP3K-MAP2K-MAPK). Thus, it seems likely that arrestins, GPCR-bound and free, facilitate the propagation of signals in these cascades, whereas signal initiation MAP3K activation may be independent of arrestins. Different MAP3Ks are activated by various inputs, some of which are mediated by G proteins, particularly in cell culture, where we artificially prevent signaling by receptor tyrosine kinases and integrins, thereby favoring GPCR-induced signaling. Thus, there is no reason to change the paradigm: Arrestins and G proteins play distinct non-overlapping roles in cell signaling.
Role of STIM1 in neurodegeneration.
Pascual-Caro C, Espinosa-Bermejo N, Pozo-Guisado E … +1 more , Martin-Romero FJ
World J Biol Chem · 2018 Nov · PMID 30568747 · Full text
STIM1 is an endoplasmic reticulum (ER) protein with a key role in Ca mobilization. Due to its ability to act as an ER-intraluminal Ca sensor, it regulates store-operated Ca entry (SOCE), which is a Ca influx pathway invo...
STIM1 is an endoplasmic reticulum (ER) protein with a key role in Ca mobilization. Due to its ability to act as an ER-intraluminal Ca sensor, it regulates store-operated Ca entry (SOCE), which is a Ca influx pathway involved in a wide variety of signalling pathways in eukaryotic cells. Despite its important role in Ca transport, current knowledge about the role of STIM1 in neurons is much more limited. Growing evidence supports a role for STIM1 and SOCE in the preservation of dendritic spines required for long-term potentiation and the formation of memory. In this regard, recent studies have demonstrated that the loss of STIM1, which impairs Ca mobilization in neurons, risks cell viability and could be the cause of neurodegenerative diseases. The role of STIM1 in neurodegeneration and the molecular basis of cell death triggered by low levels of STIM1 are discussed in this review.
Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease.
Fujii J, Homma T, Kobayashi S … +1 more , Seo HG
World J Biol Chem · 2018 Oct · PMID 30364769 · Full text
Reactive oxygen species (ROS) are produced during normal physiologic processes with the consumption of oxygen. While ROS play signaling roles, when they are produced in excess beyond normal antioxidative capacity this ca...
Reactive oxygen species (ROS) are produced during normal physiologic processes with the consumption of oxygen. While ROS play signaling roles, when they are produced in excess beyond normal antioxidative capacity this can cause pathogenic damage to cells. The majority of such oxidation occurs in polyunsaturated fatty acids and sulfhydryl group in proteins, resulting in lipid peroxidation and protein misfolding, respectively. The accumulation of misfolded proteins in the endoplasmic reticulum (ER) is enhanced under conditions of oxidative stress and results in ER stress, which, together, leads to the malfunction of cellular homeostasis. Multiple types of defensive machinery are activated in unfolded protein response under ER stress to resolve this unfavorable situation. ER stress triggers the malfunction of protein secretion and is associated with a variety of pathogenic conditions including defective insulin secretion from pancreatic β-cells and accelerated lipid droplet formation in hepatocytes. Herein we use nonalcoholic fatty liver disease (NAFLD) as an illustration of such pathological liver conditions that result from ER stress in association with oxidative stress. Protecting the ER by eliminating excessive ROS the administration of antioxidants or by enhancing lipid-metabolizing capacity the activation of peroxisome proliferator-activated receptors represent promising therapeutics for NAFLD.
at the interface between intermediary metabolism and oncogenesis.
Pajares MÁ
World J Biol Chem · 2017 Nov · PMID 29225734 · Full text
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damage-regulated gene 1 () gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression...
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damage-regulated gene 1 () gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase II complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.
Control of nuclear-cytoplasmic shuttling of Ankrd54 by PKCδ.
Samuels AL, Louw A, Zareie R … +1 more , Ingley E
World J Biol Chem · 2017 Aug · PMID 28924458 · Full text
AIM: To identify and characterize the effect of phosphorylation on the subcellular localization of Ankrd54. METHODS: HEK293T cells were treated with calyculin A, staurosporin or phorbol 12-myristate 13-acetate (PMA). Cel...
AIM: To identify and characterize the effect of phosphorylation on the subcellular localization of Ankrd54. METHODS: HEK293T cells were treated with calyculin A, staurosporin or phorbol 12-myristate 13-acetate (PMA). Cells were transfected with eGFP-tagged Ankrd54 with or without Lyn tyrosine kinase (wild-type, mutant, or mutant). The subcellular localization was assessed by immunofluorescence imaging of cells, immunoblotting of subcellular fractionations. The phosphorylation of Ankrd54 was monitored using Phos-tagTM gel retardation. Phosphorylated peptides were analysed by multiple-reaction-monitoring (MRM) proteomic analysis. RESULTS: Activation of PKC kinases using PMA promoted nuclear export of Ankrd54 and correlated with increased Ankrd54 phosphorylation, assayed using Phos-tagTM gel retardation. Co-expression of an active form of the PKCδ isoform specifically promoted both phosphorylation and cytoplasmic localization of Ankrd54, while PKCδ, Akt and PKA did not. Alanine mutation of several serine residues in the amino-terminal region of Ankrd54 (Ser14, Ser17, Ser18, Ser19) reduced both PMA induced cytoplasmic localization and phosphorylation of Ankrd54. Using MRM proteomic analysis, phosphorylation of the Ser18 residue of Ankrd54 was readily detectable in response to PMA stimulation. PMA stimulation of cells co-expressing Ankrd54 and Lyn tyrosine kinase displayed increased co-immunoprecipitation and enhanced co-localization in the cytoplasm. CONCLUSION: We identify phosphorylation by PKCδ as a major regulator of nuclear-cytoplasmic shuttling of Ankrd54, and its interaction with the tyrosine kinase Lyn.
B-1 cells modulate the murine macrophage response to infection.
Arcanjo AF, Nunes MP, Silva-Junior EB … +5 more , Leandro M, da Rocha JDB, Morrot A, Decote-Ricardo D, Freire-de-Lima CG
World J Biol Chem · 2017 May · PMID 28588758 · Full text
AIM: To investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with () . METHODS: Peritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with and cultured in the...
AIM: To investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with () . METHODS: Peritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with and cultured in the presence or absence of B-1 cells obtained from wild-type BALB/c mice. Intracellular amastigotes were counted, and interleukin-10 (IL-10) production was quantified in the cellular supernatants using an enzyme-linked immunosorbent assay. The levels of the lipid mediator prostaglandin E2 (PGE) were determined using a PGE enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI), and the number of lipid bodies was quantified in the cytoplasm of infected macrophages in the presence and absence of B-1 cells. Culturing the cells with selective PGE-neutralizing drugs inhibited PGE production and confirmed the role of this lipid mediator in IL-10 production. In contrast, we demonstrated that B-1 cells derived from IL-10 KO mice did not favor the intracellular growth of . RESULTS: We report that B-1 cells promote the growth of amastigotes inside peritoneal murine macrophages. We demonstrated that the modulatory effect was independent of physical contact between the cells, suggesting that soluble factor(s) were released into the cultures. We demonstrated in our co-culture system that B-1 cells trigger IL-10 production by -infected macrophages. Furthermore, the increased secretion of IL-10 was attributed to the presence of the lipid mediator PGE in supernatants of -infected macrophages. The presence of B-1 cells also favors the production of lipid bodies by infected macrophages. In contrast, we failed to obtain the same effect on parasite replication inside -infected macrophages when the B-1 cells were isolated from IL-10 knockout mice. CONCLUSION: Our results show that elevated levels of PGE and IL-10 produced by B-1 cells increase growth, as indicated by the number of parasites in cell cultures.
Identification of neuron selective androgen receptor inhibitors.
Otto-Duessel M, Tew BY, Vonderfecht S … +2 more , Moore R, Jones JO
World J Biol Chem · 2017 May · PMID 28588757 · Full text
AIM: To identify neuron-selective androgen receptor (AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, a neuromuscular disorder in which...
AIM: To identify neuron-selective androgen receptor (AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy (SBMA), or Kennedy's disease, a neuromuscular disorder in which deterioration of motor neurons leads to progressive muscle weakness. METHODS: Cell lines representing prostate, kidney, neuron, adipose, and muscle tissue were developed that stably expressed the CFP-AR-YFP FRET reporter. We used these cells to screen a library of small molecules for cell type-selective AR inhibitors. Secondary screening in luciferase assays was used to identify the best cell-type specific AR inhibitors. The mechanism of action of a neuron-selective AR inhibitor was examined using luciferase reporter assays, immunofluorescence microscopy, and immunoprecipitations. Rats were treated with the most potent compound and tissue-selective AR inhibition was examined using RT-qPCR of AR-regulated genes and immunohistochemistry. RESULTS: We identified the thiazole class of antibiotics as compounds able to inhibit AR signaling in a neuronal cell line but not a muscle cell line. One of these antibiotics, thiostrepton is able to inhibit the activity of both wild type and polyglutamine expanded AR in neuronal GT1-7 cells with nanomolar potency. The thiazole antibiotics are known to inhibit FOXM1 activity and accordingly, a novel FOXM1 inhibitor FDI-6 also inhibited AR activity in a neuron-selective fashion. The selective inhibition of AR is likely indirect as the varied structures of these compounds would not suggest that they are competitive antagonists. Indeed, we found that FOXM1 expression correlates with cell-type selectivity, FOXM1 co-localizes with AR in the nucleus, and that shRNA-mediated knock down of FOXM1 reduces AR activity and thiostrepton sensitivity in a neuronal cell line. Thiostrepton treatment reduces FOXM1 levels and the nuclear localization of beta-catenin, a known co-activator of both FOXM1 and AR, and reduces the association between beta-catenin and AR. Treatment of rats with thiostrepton demonstrated AR signaling inhibition in neurons, but not muscles. CONCLUSION: Our results suggest that thiazole antibiotics, or other inhibitors of the AR-FOXM1 axis, can inhibit AR signaling selectively in motor neurons and may be useful in the treatment or prevention of SBMA symptoms.
Immunological aspects of age-related diseases.
Isobe KI, Nishio N, Hasegawa T
World J Biol Chem · 2017 May · PMID 28588756 · Full text
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hem...
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of naïve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by anti-inflammatory (M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to age-related diseases. Underlying biochemical and metabolic studies will open nutritional treatment.
Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity.
Pirola L, Ferraz JC
World J Biol Chem · 2017 May · PMID 28588755 · Full text
In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Mass...
In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Massive adipose tissue (AT) infiltration by pro-inflammatory M1 macrophages and several T cell subsets as obesity develops leads to the accumulation - both in the AT and systemically - of numerous pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor α, IL-17 and IL-6 which are strongly associated with the progression of the obese phenotype towards the metabolic syndrome. At the same time, anti-inflammatory M2 macrophages and Th subsets producing the anti-inflammatory cytokines IL-10, IL-5 and interferon-γ, including Th2 and T-reg cells are correlated to the maintenance of AT homeostasis in lean individuals. Here, we discuss the basic principles in the control of the interaction between the AT and infiltrating immune cells both in the lean and the obese condition with a special emphasis on the contribution of pro- and anti-inflammatory cytokines to the establishment of the insulin-resistant state. In this context, we will discuss the current knowledge about alterations in the levels on pro- and anti-inflammatory cytokines in obesity, insulin resistance and type 2 diabetes mellitus, in humans and animal models. Finally, we also briefly survey the recent novel therapeutic strategies that attempt to alleviate or reverse insulin resistance and type 2 diabetes the administration of recombinant inhibitory antibodies directed towards some pro-inflammatory cytokines.
Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders.
Le Magueresse-Battistoni B, Labaronne E, Vidal H … +1 more , Naville D
World J Biol Chem · 2017 May · PMID 28588754 · Full text
Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading c...
Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, ., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules.
Common therapeutic target for both cancer and obesity.
Chang YH
World J Biol Chem · 2017 May · PMID 28588753 · Full text
Obesity and cancer are two interrelated conditions of high epidemiological need, with studies showing that obesity is responsible for nearly 25% of the relative contribution to cancer incidence. Given the connection betw...
Obesity and cancer are two interrelated conditions of high epidemiological need, with studies showing that obesity is responsible for nearly 25% of the relative contribution to cancer incidence. Given the connection between these conditions, a drug that can operate on both obesity and cancer is highly desirable. Such a drug is accomplishable through the development of potent anti-angiogenesis agents due to the shared underlying role of angiogenesis in the development of both diseases. Prior research has demonstrated a key role of type-2 methionine aminopeptidase (MetAP2) for angiogenesis, which has led to the development of numerous of novel inhibitors. Several irreversible MetAP2 inhibitors have entered clinical trials without great success. Though this lack of success could be attributed to off-target adverse effects, the underlying causes remain unclear. More promising reversible inhibitors have been recently developed with excellent pre-clinical results. However, due to insufficient knowledge of the biological functions of N-terminal protein processing, it is hard to predict whether these novel inhibitors would successfully pass clinical trials and thereby benefit cancer and obesity patients. Significantly more efforts are needed to advance our understanding of the regulation of methionine aminopeptidases and the processes by which they govern the function of proteins.
Device-associated infection rates, mortality, length of stay and bacterial resistance in intensive care units in Ecuador: International Nosocomial Infection Control Consortium's findings.
Salgado Yepez E, Bovera MM, Rosenthal VD … +13 more , González Flores HA, Pazmiño L, Valencia F, Alquinga N, Ramirez V, Jara E, Lascano M, Delgado V, Cevallos C, Santacruz G, Pelaéz C, Zaruma C, Barahona Pinto D
World J Biol Chem · 2017 Feb · PMID 28289522 · Full text
AIM: To report the results of the International Nosocomial Infection Control Consortium (INICC) study conducted in Quito, Ecuador. METHODS: A device-associated healthcare-acquired infection (DA-HAI) prospective surveilla...
AIM: To report the results of the International Nosocomial Infection Control Consortium (INICC) study conducted in Quito, Ecuador. METHODS: A device-associated healthcare-acquired infection (DA-HAI) prospective surveillance study conducted from October 2013 to January 2015 in 2 adult intensive care units (ICUs) from 2 hospitals using the United States Centers for Disease Control/National Healthcare Safety Network (CDC/NHSN) definitions and INICC methods. RESULTS: We followed 776 ICU patients for 4818 bed-days. The central line-associated bloodstream infection (CLABSI) rate was 6.5 per 1000 central line (CL)-days, the ventilator-associated pneumonia (VAP) rate was 44.3 per 1000 mechanical ventilator (MV)-days, and the catheter-associated urinary tract infection (CAUTI) rate was 5.7 per 1000 urinary catheter (UC)-days. CLABSI and CAUTI rates in our ICUs were similar to INICC rates [4.9 (CLABSI) and 5.3 (CAUTI)] and higher than NHSN rates [0.8 (CLABSI) and 1.3 (CAUTI)] - although device use ratios for CL and UC were higher than INICC and CDC/NSHN's ratios. By contrast, despite the VAP rate was higher than INICC (16.5) and NHSN's rates (1.1), MV DUR was lower in our ICUs. Resistance of to imipenem and meropenem was 75.0%, and of to ciprofloxacin and piperacillin-tazobactam was higher than 72.7%, all them higher than CDC/NHSN rates. Excess length of stay was 7.4 d for patients with CLABSI, 4.8 for patients with VAP and 9.2 for patients CAUTI. Excess crude mortality in ICUs was 30.9% for CLABSI, 14.5% for VAP and 17.6% for CAUTI. CONCLUSION: DA-HAI rates in our ICUs from Ecuador are higher than United States CDC/NSHN rates and similar to INICC international rates.
L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death.
Le Borgne F, Ravaut G, Bernard A … +1 more , Demarquoy J
World J Biol Chem · 2017 Feb · PMID 28289521 · Full text
AIM: To identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells. METHODS: Myoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders...
AIM: To identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells. METHODS: Myoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders oxidative stress, and the protective effect of L-carnitine (a nutrient involved in fatty acid metabolism and the control of the oxidative process), was assessed by monitoring various parameters related to the oxidative stress, autophagy and cell death. RESULTS: Associated with its physiological function, a muscle cell metabolism is highly dependent on oxygen and may produce reactive oxygen species (ROS), especially under pathological conditions. High levels of ROS are known to induce injuries in cell structure as they interact at many levels in cell function. In C2C12 cells, a treatment with menadione induced a loss of transmembrane mitochondrial potential, an increase in mitochondrial production of ROS; it also induces autophagy and was able to provoke cell death. Pre-treatment of the cells with L-carnitine reduced ROS production, diminished autophagy and protected C2C12 cells against menadione-induced deleterious effects. CONCLUSION: In conclusion, L-carnitine limits the oxidative stress in these cells and prevents cell death.
Use of thyroglobulin as a tumour marker.
Indrasena BS
World J Biol Chem · 2017 Feb · PMID 28289520 · Full text
It is worthwhile to measure serum thyroglobulin (TG) level in thyroid cancer before subjecting patients to surgery for two reasons. Firstly, if the level is high, it may give a clue to the local and metastatic tumour bur...
It is worthwhile to measure serum thyroglobulin (TG) level in thyroid cancer before subjecting patients to surgery for two reasons. Firstly, if the level is high, it may give a clue to the local and metastatic tumour burden at presentation; secondly, if the level is normal, it identifies the patients who are unlikely to show rising TG levels in the presence of thyroid cancer. Those who have high serum TG before surgery will show up recurrence as rising serum TG during the postoperative period. Those who do not have high serum TG before surgery will not show up rising serum TG in the presence of recurrent disease. In the latter situation, normal TG level gives only a false reassurance regarding recurrence of disease. Nevertheless, rising serum TG during the postoperative period must be interpreted cautiously because this could be due to the enlargement of non-cancerous residual thyroid tissue inadvertently left behind during surgery.
Challenges in the chemotherapy of Chagas disease: Looking for possibilities related to the differences and similarities between the parasite and host.
Sueth-Santiago V, Decote-Ricardo D, Morrot A … +2 more , Freire-de-Lima CG, Lima ME
World J Biol Chem · 2017 Feb · PMID 28289519 · Full text
Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries...
Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.
Role of microRNAs in translation regulation and cancer.
Oliveto S, Mancino M, Manfrini N … +1 more , Biffo S
World J Biol Chem · 2017 Feb · PMID 28289518 · Full text
MicroRNAs (miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathologic...
MicroRNAs (miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.
Retroviral integrase protein and intasome nucleoprotein complex structures.
Grawenhoff J, Engelman AN
World J Biol Chem · 2017 Feb · PMID 28289517 · Full text
Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase (IN) protein. IN catalyzes two distinct chemi...
Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase (IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus (PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus (RSV) and β-retrovirus mouse mammary tumor virus (MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.
Biochemical changes in the injured brain.
Sahu S, Nag DS, Swain A … +1 more , Samaddar DP
World J Biol Chem · 2017 Feb · PMID 28289516 · Full text
Brain metabolism is an energy intensive phenomenon involving a wide spectrum of chemical intermediaries. Various injury states have a detrimental effect on the biochemical processes involved in the homeostatic and electr...
Brain metabolism is an energy intensive phenomenon involving a wide spectrum of chemical intermediaries. Various injury states have a detrimental effect on the biochemical processes involved in the homeostatic and electrophysiological properties of the brain. The biochemical markers of brain injury are a recent addition in the armamentarium of neuro-clinicians and are being increasingly used in the routine management of neuro-pathological entities such as traumatic brain injury, stroke, subarachnoid haemorrhage and intracranial space occupying lesions. These markers are increasingly being used in assessing severity as well as in predicting the prognostic course of neuro-pathological lesions. S-100 protein, neuron specific enolase, creatinine phosphokinase isoenzyme BB and myelin basic protein are some of the biochemical markers which have been proven to have prognostic and clinical value in the brain injury. While S-100, glial fibrillary acidic protein and ubiquitin C terminal hydrolase are early biomarkers of neuronal injury and have the potential to aid in clinical decision-making in the initial management of patients presenting with an acute neuronal crisis, the other biomarkers are of value in predicting long-term complications and prognosis in such patients. In recent times cerebral microdialysis has established itself as a novel way of monitoring brain tissue biochemical metabolites such as glucose, lactate, pyruvate, glutamate and glycerol while small non-coding RNAs have presented themselves as potential markers of brain injury for future.
Biochemical strategies for the detection and detoxification of toxic chemicals in the environment.
Febbraio F
World J Biol Chem · 2017 Feb · PMID 28289515 · Full text
Addressing the problems related to the widespread presence of an increasing number of chemicals released into the environment by human activities represents one of the most important challenges of this century. In the la...
Addressing the problems related to the widespread presence of an increasing number of chemicals released into the environment by human activities represents one of the most important challenges of this century. In the last few years, to replace the high cost, in terms of time and money, of conventional technologies, the scientific community has directed considerable research towards the development both of new detection systems for the measurement of the contamination levels of chemicals in people's body fluids and tissue, as well as in the environment, and of new remediation strategies for the removal of such chemicals from the environment, as a means of the prevention of human diseases. New emerging biosensors for the analysis of environmental chemicals have been proposed, including VHH antibodies, that combine the antibody performance with the affinity for small molecules, genetically engineered microorganisms, aptamers and new highly stable enzymes. However, the advances in the field of chemicals monitoring are still far from producing a continuous real-time and on-line system for their detection. Better results have been obtained in the development of strategies which use organisms (microorganisms, plants and animals) or metabolic pathway-based approaches (single enzymes or more complex enzymatic solutions) for the fixation, degradation and detoxification of chemicals in the environment. Systems for enzymatic detoxification and degradation of toxic agents in wastewater from chemical and manufacturing industries, such as ligninolytic enzymes for the treatment of wastewater from the textile industry, have been proposed. Considering the high value of these research studies, in terms of the protection of human health and of the ecosystem, science must play a major role in guiding policy changes in this field.
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