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1.
ESMO Open ; 7(2): 100406, 2022 04.
Article in English | MEDLINE | ID: mdl-35219245

ABSTRACT

INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.


Subject(s)
COVID-19 , Lung Neoplasms , Communicable Disease Control , Humans , Italy/epidemiology , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Pandemics
2.
J Biosci ; 462021.
Article in English | MEDLINE | ID: mdl-34168101

ABSTRACT

This study reports for the first-time antioxidant activity and flavonoid composition of KP onion landrace which is useful for future breeding programs and to obtain geographical indication (GI) tag for the benefit of farmers. The present study was aimed to determine antioxidant capacity and flavonoid composition of bulbs of red onion (Allium cepa L.) landrace 'Krishnapuram' (KP) from India using high-performance liquid chromatography (HPLC)-Electrospray Ionization (ESI)-multistage Ion Trap Mass Spectrometry (ITMS). The antioxidant activity was assayed by Ferric Reducing Antioxidant Power (FRAP) and hypochlorous acid (HClO)-induced oxidative damage in human erythrocytes. The total phenolic (TPC) contents in KP onion bulb extract (with 80% methanol) found to be 1.10 ± 0.2 mg GAE/g FW and 38.88 ± 1.0 lM QE/g. The FRAP activity measured for the bulb extract was 13.20 ± 0.1 µM QE/g. KP onion bulb extracts protected red blood cells (RBC) effectively (23%) against the oxidative damage induced by HClO. HPLC-ESI-ITMS analysis showed the presence of eight flavonols and five anthocyanins. Quercetin 3,4' -O-diglucoside (384.71 ± 0.49 mg/kg FW) and cyanidin 3-(6″-malonylglucoside) (20.95 ± 0.60 mg/kg FW) were detected as major flavonol and anthocyanin, respectively. The study suggests that KP onion has a considerable antioxidant activity due to the presence of high TPC. Moreover, quercetin glucosides are found to be more abundant than quercetin. The differences in quercetin glycosides content among different red onions could be useful for breeding programmes in the future.


Subject(s)
Antioxidants/analysis , Flavonoids/analysis , Onions/chemistry , Chromatography, High Pressure Liquid , Plant Roots/chemistry , Spectrometry, Mass, Electrospray Ionization
3.
Arch Biochem Biophys ; 583: 150-7, 2015 Oct 01.
Article in English | MEDLINE | ID: mdl-26297952

ABSTRACT

Novel therapies for rheumatoid arthritis also include the use of naturally occurring compounds possessing antioxidant properties. In the present work, the effects of oral administration of quercetin were investigated in a rat model of adjuvant arthritis. Arthritis was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experimental groups were treated with an oral daily dose of 150 mg/kg b.w. of quercetin for 28 days. Results indicated that quercetin was able to ameliorate all markers of inflammation and oxidative stress measured. Quercetin lowered levels of interleukin-1ß, C-reactive protein, and monocyte chemotactic protein-1 and restored plasma antioxidant capacity. In addition, quercetin inhibited the enzymatic activity of pro-inflammatory 12/15-lipoxygenase in lung and liver and increased the expression of heme oxygenase-1 in joint and lung of arthritic rats. Finally, quercetin inhibited the 2-fold increase of NF-қB activity observed in lung, liver and joint after induction of arthritis.


Subject(s)
Antioxidants/metabolism , Arthritis, Experimental/prevention & control , Inflammation/prevention & control , Quercetin/pharmacology , Animals , Arthritis, Experimental/blood , Arthritis, Experimental/metabolism , Inflammation/blood , Inflammation/metabolism , Lipoxygenases/metabolism , Liver/drug effects , Liver/enzymology , Lung/drug effects , Lung/enzymology , NF-kappa B/metabolism , Rats , Rats, Inbred Lew
4.
Anticancer Agents Med Chem ; 15(7): 888-95, 2015.
Article in English | MEDLINE | ID: mdl-25909897

ABSTRACT

Nowadays, dietary guidelines acknowledge the therapeutic role of omega-3 polyunsaturated fatty acids, as the most important class of fatty acids, against different human diseases. During the last two decades, the average level of consumption of omega-3 polyunsaturated fatty acids has increased from 0.1 to 0.2 g per day. Omega-3 polyunsaturated fatty acids are a group of long-chain polyunsaturated fatty acids which are identified in different foods such as fatty fish, shellfish, and vegetable oils. A growing body of epidemiological and experimental evidence supports the anticancer effects of omega-3 polyunsaturated fatty acids, which led to the identification of their molecular targets in several cancer models. The present review focuses on the basic evidence supporting the potential applications of omega-3 polyunsaturated fatty acids in cancer therapy.


Subject(s)
Anticarcinogenic Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Fatty Acids, Omega-3/therapeutic use , Neoplasms/drug therapy , Anticarcinogenic Agents/pharmacology , Antineoplastic Agents/pharmacology , Cell Death/drug effects , Cell Proliferation/drug effects , Fatty Acids, Omega-3/pharmacology , Humans , Inflammation/metabolism , Molecular Targeted Therapy , Neoplasm Metastasis , Neoplasms/blood supply , Neoplasms/metabolism , Neoplasms/pathology , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Signal Transduction/drug effects , Transcription Factors/antagonists & inhibitors
5.
Zygote ; 23(1): 11-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-23673140

ABSTRACT

Several genetic and physiological factors increase the risk of DNA damage in mammalian oocytes. Two critical events are: (i) meiosis progression, from maturation to fertilization, due to extensive chromatin remodelling during genome decondensation; and (ii) aging, which is associated with a progressive oxidative stress. In this work, we studied the transcriptional patterns of three genes, RAD51, APEX-1 and MLH1, involved in DNA repair mechanisms. The analyses were performed by real-time quantitative PCR (RT-qPCR) in immature and in vitro matured oocytes collected from 17 ± 3-month-old heifers and 94 ± 20-month-old cows. Batches of 30-50 oocytes for each group (three replicates) were collected from ovarian follicles of slaughtered animals. The oocytes were freed from cumulus cells at the time of follicle removal, or after in vitro maturation (IVM) carried out in M199 supplemented with 10% fetal calf serum, 10 IU luteinising hormone (LH)/ml, 0.1 IU follicle-stimulating hormone (FSH)/ml and 1 µg 17ß-oestradiol/ml. Total RNA was extracted by Trizol method. The expression of bovine GAPDH gene was used as the internal standard, while primers for bovine RAD51, APEX-1 and MLH1 genes were designed from DNA sequences retrieved from GenBank. Results obtained indicate a clear up-regulation of RAD51, APEX-1 and MLH1 genes after IVM, ranging between two- and four-fold compared with germinal vesicle (GV) oocytes. However, only RAD51 showed a significant transcript increase between the immature oocytes collected from young or old individuals. This finding highlights RAD51 as a candidate gene marker for discriminating bovine immature oocytes in relation to the donor age.


Subject(s)
DNA Repair/genetics , Meiosis , Oocytes/physiology , Age Factors , Animals , Cattle , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , Female , Gene Expression Profiling , In Vitro Oocyte Maturation Techniques , Nuclear Proteins/genetics , Rad51 Recombinase/genetics
6.
Food Chem Toxicol ; 60: 377-84, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23933363

ABSTRACT

Until recently, the supposed preventive effects of red wine against cardiovascular diseases, the so-called "French Paradox", has been associated to its antioxidant properties. The interest in the anticancer capacity of polyphenols present in red wine strongly increased consequently to the enormous number of studies on resveratrol. In this study, using lyophilized red wine, we present evidence that its anticancer effect in a cellular model is mediated by apoptotic and autophagic cell death. Using a human osteosarcoma cell line, U2Os, we found that the lyophilized red wine was cytotoxic in a dose-dependent manner with a maximum effect in the range of 100-200 µg/ml equivalents of gallic acid. A mixed phenotype of types I/II cell death was evidenced by means of specific assays following treatment of U2Os with lyophilized red wine, e.g., autophagy and apoptosis. We found that cell death induced by lyophilized red wine proceeded through a mechanism independent from its anti-oxidant activity and involving the inhibition of PI3K/Akt kinase signaling. Considering the relative low concentration of each single bioactive compound in lyophilized red wine, our study suggests the activation of synergistic mechanism able to inhibit growth in malignant cells.


Subject(s)
Alcohols/analysis , Apoptosis/drug effects , Autophagy/drug effects , Wine/analysis , Antioxidants/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Freeze Drying , Humans , Osteosarcoma/metabolism , Polyphenols/pharmacology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species , Resveratrol , Signal Transduction , Stilbenes/pharmacology
7.
Gen Comp Endocrinol ; 178(1): 54-63, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22531466

ABSTRACT

Endocrine disruptor chemicals (EDCs), which are predominantly present in the environment, are able to mimic or antagonise the biological activity of hormones primarily through the interaction with specific receptors. The main consequences are adverse effects on the growth and development of reproductive organs, the induction of cancer and effects on neuronal differentiation. In this study, we investigated the ability of certain EDCs, Bisphenol A (BPA), Bisphenol B (BPB), Bisphenol F (BPF), 4-n Nonylphenol (NP) and Octylphenol (OP), belonging to a homogeneous group of phenol origin, to interfere with specific cellular processes, namely, proliferation, by using MCF-7 breast carcinoma cells, and differentiation, by using murine bone marrow dendritic cells. We correlated the data on cell growth with the stimulation of cell cycle progression, which could become a step in the development of cancer, and we established a proliferation ranking between the tested EDCs: NP>BPA>OP>BPB>BPF. In addition, we investigated the ability of NP, BPA and OP to induce the differentiation of dendritic cells, the powerful antigen-presenting cells of the immune system. The differentiation and activation of these cells could affect a well-regulated immune response and determine an allergic sensitisation. We found that BPA and NP were active in determining differentiation.


Subject(s)
Cell Cycle/drug effects , Cell Differentiation/drug effects , Dendritic Cells/cytology , Dendritic Cells/drug effects , Endocrine Disruptors/pharmacology , Animals , Benzhydryl Compounds , Cell Line, Tumor , Cells, Cultured , Female , Humans , Mice , Mice, Inbred C57BL , Phenols/pharmacology
8.
Br J Cancer ; 105(2): 221-30, 2011 Jul 12.
Article in English | MEDLINE | ID: mdl-21750559

ABSTRACT

BACKGROUND: We recently demonstrated that quercetin, a flavonoid naturally present in food and beverages belonging to the large class of phytochemicals, was able to sensitise leukaemic cells isolated from patients with chronic lymphocytic leukaemia (CLL) when associated with recombinant tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or anti-CD95. We also showed that quercetin potentiated the effect of fludarabine on resistant B cells from CLL patients. Resistance to therapy in CLL depends on the expression and activity of anti-apoptotic proteins of the Bcl-2 family. Among these, myeloid cell leukaemia-1 (Mcl-1) has been associated with apoptotic resistance in CLL. Therefore, we investigate here whether the sensitising activity of this flavonoid, which leads to increased apoptosis in both cell lines and CLL, could be related to Mcl-1 expression and stability. RESULTS: B cells isolated from CLL patients showed different levels of Mcl-1 protein expression, resulting, in several cases, in increased sensitivity to fludarabine. Quercetin significantly enhanced the downregulation of Mcl-1 in B cells isolated from selected patients expressing detectable levels of Mcl-1. In U-937 cells, quercetin increased Mcl-1 mRNA instability in the presence of actinomycin D. When cells were treated with MG-132, a proteasome inhibitor, Mcl-1 protein level increased. However, quercetin, in the presence of Z-Vad-FMK, continued to lower Mcl-1 protein expression, indicating its independence from caspase-mediated degradation. In contrast, co-treatment of quercetin and MG-132 did not revert the effect of MG-132 mono-treatment, thus suggesting a possible interference of quercetin in regulating the proteasome-dependent degradation of Mcl-1. Gossypol, a small-molecule inhibitor of Bcl-2 family members, mimics the activity of quercetin by lowering Mcl-1 expression and sensitising U-937 cells to apoptosis induced by recombinant TRAIL and the Fas-ligand. CONCLUSION: This study demonstrates that in U-937 cells, quercetin downregulates Mcl-1 acting directly or indirectly on its mRNA stability and protein degradation, suggesting that the same mechanism may bypass resistance to apoptosis in leukaemic cells isolated from CLL patients and sensitise B cells to apoptosis induced by drugs and death receptor inducers.


Subject(s)
Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Quercetin/pharmacology , RNA Stability/drug effects , RNA, Messenger/drug effects , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Down-Regulation/drug effects , Down-Regulation/genetics , Drug Evaluation, Preclinical , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Drug Synergism , Gene Expression Regulation, Leukemic/drug effects , Gossypol/pharmacology , Humans , Myeloid Cell Leukemia Sequence 1 Protein , Protein Processing, Post-Translational/drug effects , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , RNA, Messenger/metabolism , Tumor Cells, Cultured , U937 Cells
9.
Epidemiol Psychiatr Sci ; 20(1): 99-105, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21657120

ABSTRACT

OBJECTIVE: The primary goal was to identify risk factors for post-surgical depression in subjects operated on for drug-resistant epilepsy. Secondary goals were to confirm the high rate of depression in subjects suffering from epilepsy (prior to surgery) and to look for first post-surgical depressive episode. METHODS: Case series study of 150 subjects surgically treated for partial epilepsy (side of surgery: 72 right, 78 left; site of surgery: 97 Unilobar Temporal, 17 Unilobar Frontal, 14 Posterior, 22 Multilobar). All subjects routinely had three psychiatric evaluations: before surgery (baseline) and at 6 and 12 months after surgery. Psychiatric diagnoses were made according to DSM-IV-TR criteria. Bivariate (Fisher exact test and Kruskal-Wallis rank sum test) and multivariate (logistic regression model fitting) analyses were performed. RESULTS: Thirty-three (22%) subjects had post-surgical depressive episodes, 31 of them in the first 6 months. Fourteen out of 33 experienced depression for the first time. Post-surgical depressive episodes are not associated with gender, outcome on seizures, side/site of surgical resection, histological diagnosis, psychiatric diagnoses other than depression. Depressive episodes before surgery and older age at surgery time are risk factors for post-surgical depression (p= 0.0001 and 0.01, respectively, at logistic regression analysis). No protective factors were identified. CONCLUSIONS: Our data show that lifetime depressive episodes and older age at surgery time are risk factors for postsurgery depression. Moreover, a prospective study could be useful in order to assess whether depression is really a consequence of surgery.


Subject(s)
Depressive Disorder/diagnosis , Epilepsies, Partial/surgery , Postoperative Complications/diagnosis , Adult , Age Factors , Cross-Sectional Studies , Depressive Disorder/epidemiology , Depressive Disorder/psychology , Female , Humans , Male , Postoperative Complications/epidemiology , Postoperative Complications/psychology , Recurrence , Risk Factors
10.
Br J Cancer ; 103(5): 642-8, 2010 Aug 24.
Article in English | MEDLINE | ID: mdl-20648016

ABSTRACT

BACKGROUND: Quercetin is a flavonoid naturally present in food and beverages belonging to the large class of phytochemicals with potential anti-cancer properties. Here, we investigated the ability of quercetin to sensitise primary cells from chronic lymphocytic leukaemia (CLL) to death receptor (DR) agonists, recombinant TNF-related-apoptosis-inducing ligand (rTRAIL) and anti-CD95, and to fludarabine, a widely used chemotherapeutic drug against CLL. METHODS: Peripheral white blood cells were isolated from patients and incubated with medium containing 50 ng ml anti-CD95 agonist antibody; 10 ng ml recombinant TRAIL; 10-25 microM quercetin and 3.5-14 microM fludarabine. Neutral Red assay was used to measure cell viability, where as apoptosis was assessed by determining caspase-3 activity, exposure to Annexin V and PARP fragmentation. RESULTS: Quercetin significantly enhanced anti-CD95- and rTRAIL-induced cell death as shown by decreased cell viability, increased caspase-3 and -9 activities, and positivity to Annexin V. In addition, association of quercetin with fludarabine increases the apoptotic response in CLL cells of about two-fold compared with quercetin monotreatment. CONCLUSION: This work shows that resistance to DR- and fludarabine-induced cell death in leukaemic cells isolated from CLL patients can be ameliorated or bypassed by the combined treatment with quercetin. Considering the low toxicity of the molecule, our study results are in favour of a potential use of quercetin in adjuvant chemotherapy in combination with other drugs.


Subject(s)
Apoptosis/drug effects , Quercetin/pharmacology , Receptors, Death Domain/agonists , TNF-Related Apoptosis-Inducing Ligand/pharmacology , Adult , Aged, 80 and over , Cells, Cultured , Drug Synergism , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Male , Recombinant Proteins/pharmacology , Vidarabine/analogs & derivatives , fas Receptor/antagonists & inhibitors
11.
Neurology ; 73(10): 746-53, 2009 Sep 08.
Article in English | MEDLINE | ID: mdl-19535771

ABSTRACT

OBJECTIVE: To define distinctive features of nodular heterotopia in specimens derived from drug-resistant patients with epilepsy by evaluating mRNA expression of three different layer-specific markers: Rorbeta, Er81, and Nurr1. METHODS: We analyzed the expression profile of these genes, recognized as markers mainly expressed in layer IV for Rorbeta, in layer V for Er81, and in layer VI for Nurr1, in surgical samples from 14 epileptic patients, using in situ hybridization. Six patients had subcortical nodular heterotopia and 8 patients were controls. The intrinsic organization of nodular formations and of the overlaying neocortex was assessed. RESULTS: In all patients, the 3 selected genes showed high cortical laminar specificity. In subcortical nodular heterotopia, the different gene expression profiles revealed a rudimentary laminar organization of the nodules. In the overlaying cortex, fewer cells expressed the 3 genes in the appropriate specific layer as compared to controls. CONCLUSIONS: These data provide new insights into possible ontogenetic mechanisms of nodular heterotopia formation and show the potential role of layer-specific markers to elucidate the neuropathology of malformations of cortical development.


Subject(s)
Cerebral Cortex/abnormalities , Cerebral Cortex/pathology , Periventricular Nodular Heterotopia/genetics , Periventricular Nodular Heterotopia/pathology , Adolescent , Adult , Cerebral Cortex/physiology , Child , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Female , Gene Expression Profiling/methods , Genetic Markers/genetics , Humans , Male , Malformations of Cortical Development/genetics , Malformations of Cortical Development/pathology , Nuclear Receptor Subfamily 1, Group F, Member 2 , Nuclear Receptor Subfamily 4, Group A, Member 2 , Receptors, Cytoplasmic and Nuclear/biosynthesis , Receptors, Cytoplasmic and Nuclear/genetics , Transcription Factors/biosynthesis , Transcription Factors/genetics , Young Adult
13.
J Appl Microbiol ; 101(1): 234-41, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16834611

ABSTRACT

AIMS: The aim of this research was to identify and partially purify new bacteriocin-like substances from strains of halophilic 'non-cholera' vibrios isolated from food sources. METHODS AND RESULTS: Forty-five halophilic Vibrio spp. strains were screened for antimicrobial production. Vibrio mediterranei 1, a nonpathogenic strain, showed antimicrobial activity towards Vibrio parahaemolyticus spp. and related species. The bacteriocin-like inhibitory substance (BLIS), released by the bacteria into growth media, was concentrated by ultrafiltration and characterized. BLIS was sensitive to proteinase K, was stable in the pH range 5-9, was resistant to organic solvents and was heat stable up to 75 degrees C. Initial purification of BLIS by size exclusion chromatography showed an apparent molecular mass of 63-65 kDa. CONCLUSIONS: This study reports the ability of V. mediterranei 1 to produce a bacteriocin-like substance inhibiting growth of V. parahaemolyticus spp. and other closely related bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The strong activity of BLIS towards the human and fish pathogen V. parahaemolyticus and the persistence of antimicrobial properties under a variety of different conditions suggest its potential application in food microbiology.


Subject(s)
Antibiosis/physiology , Bacteriocins/biosynthesis , Food Microbiology , Vibrio/metabolism , Water Microbiology , Bacteriocins/isolation & purification , Chymotrypsin/pharmacology , Endopeptidase K/pharmacology , Hydrogen-Ion Concentration , Microbial Sensitivity Tests , Solvents/pharmacology , Temperature , Trypsin/pharmacology , Vibrio parahaemolyticus/drug effects
14.
Cell Mol Life Sci ; 62(14): 1641-52, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15990955

ABSTRACT

p27BBP/eIF6 is an evolutionarily conserved regulator of ribosomal function. It is necessary for 60S biogenesis and impedes improper joining of 40S and 60S subunits, regulated by protein kinase C or Efl1p. No data on p27BBP/eIF6 during early development of Metazoa are available. We studied the distribution, post-translational changes and association with the cytoskeleton of p27BBP/ eIF6 during Xenopus oogenesis and early development. Results indicate that p27BBP/eIF6 is present throughout oogenesis, partly associated with 60S subunits, partly free and with little cytoskeleton bound. During prophase I, p27BBP/eIF6 is detected as a single band of 27-kDa. Upon maturation induced by progesterone or protein kinase C, a serine-phosphorylated 29 kDa isoform appears and is kept throughout development to the neurula stage. Confocal microscopy showed that the distribution of p27BBP/eIF6 and its association with the cytoskeleton varies according to oogenesis stages. Briefly, in stage 6 oocytes, p27BBP/eIF6 has a limited dot-like distribution, and does not co-localize with cytokeratin, whereas upon maturation it spreads throughout the cytoplasm. After fertilization, a large fraction coalesces around cytomembranes and a cytochalasin B-sensitive co-localization with cytokeratin occurs. RNAse removes p27BBP/eIF6 from the cytokeratin fibres. Developmental data suggest a role of p27BBP/eIF6 in controlling ribosomal availability or regulating cross-talk between ribosomes and the cytoskeleton.


Subject(s)
Carrier Proteins/metabolism , Cytoskeleton/metabolism , Intermediate Filament Proteins/metabolism , Oogenesis , Xenopus Proteins/metabolism , Animals , Blotting, Western , Carrier Proteins/chemistry , Electrophoresis, Polyacrylamide Gel , Eukaryotic Initiation Factors , Female , Immunohistochemistry , Intermediate Filament Proteins/chemistry , Male , Meiosis , Microscopy, Confocal , Molecular Weight , Oocytes/drug effects , Oocytes/growth & development , Oocytes/metabolism , Phosphoric Monoester Hydrolases/metabolism , Phosphorylation , Phosphoserine/metabolism , Progesterone/pharmacology , Protein Binding , Ribosomes/metabolism , Time Factors , Xenopus Proteins/chemistry , Xenopus laevis , Zygote/metabolism
15.
Article in English | MEDLINE | ID: mdl-15369832

ABSTRACT

This study reports titration of vitamin E levels in the sea bass (Dicentrarchus labrax) using high-pressure liquid chromatography. The first part of the work is devoted to vitamin E detection in: (1) plasma of maturing females and males characterized by different body sizes; (2) seminal fluid and eggs; and (3) developing embryos of sea bass fed with vitamin E. In the second part of the study, variations of vitamin E levels during larval development are analyzed. The results show a direct correlation between plasma vitamin E content and body size for both adult male and female sea bass. High vitamin E levels were found in seminal fluid, in eggs before and after fertilization, and in embryos during development and at hatching, whereas vitamin E level was low in dead embryos and in embryos with limited survival. During larval development, the vitamin E content decreased slowly but steadily during the first four days of larval growth; subsequently, it progressively increased from day 9 to day 40. In teratogenic larvae, vitamin E content was significantly higher than in normal larvae. This study provides evidence on how vitamin E exerts an antioxidant defense in sea bass reproduction.


Subject(s)
Bass/embryology , Bass/growth & development , Vitamin E/metabolism , Animals , Bass/blood , Bass/metabolism , Body Size , Body Weight , Embryo, Nonmammalian/chemistry , Embryo, Nonmammalian/metabolism , Female , Fertilization/physiology , Larva/chemistry , Larva/growth & development , Larva/metabolism , Male , Ovum/chemistry , Ovum/metabolism , Time Factors , Vitamin E/analysis , Vitamin E/blood
16.
Food Chem Toxicol ; 41(10): 1367-74, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12909270

ABSTRACT

Melanoidins, the brown-colored polymers formed through Maillard type reaction in several heat-treated foods, represent a significant part of our diet, with an average intake of grams per day. Most of the studies on the physiological effects of these compounds have been performed using the water soluble melanoidin fractions. But dietary melanoidins formed on the surface of bakery products are poorly soluble in water as well as in organic solvents. In this work, an enzymatic solubilization procedure was developed on a gluten-glucose model system and it was applied to bread and biscuits. The soluble material obtained was tested for its antioxidant activity, for its effect on phase-I and phase-II xenobiotic enzymes and for potential cytotoxic effects. Soluble melanoidins from model system and biscuits exhibit a strong antioxidant activity and do not show any cytotoxicity on Caco-2 cells. Melanoidins extracted from biscuits was able to inhibit the activity of Phase I (NADPH-cytochrome-c reductase) and Phase II (Glutathione-S-transferase) enzymes, whereas the low molecular weight melanoidins isolated from gluten-glucose model system inhibit the activity of NADPH-cytochrome-c reductase.


Subject(s)
Bread/analysis , Bread/toxicity , Polymers/chemistry , Polymers/toxicity , Antioxidants/chemistry , Caco-2 Cells , Cell Survival/drug effects , Glutathione Reductase/metabolism , Glutens/chemistry , Hot Temperature , Humans , Hydrolysis , Kinetics , Molecular Weight , NADPH-Ferrihemoprotein Reductase/metabolism , Pronase/chemistry , Trichloroacetic Acid/chemistry , Xenobiotics/metabolism
17.
Nutr Metab Cardiovasc Dis ; 13(5): 291-300, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14717062

ABSTRACT

AIM: Cardiovascular disease (CVD) is the term used to define a group of disorders of the heart and blood vessels. Apoptosis, also known as programmed cell death (PCD), is genetically programmed "cell suicide" that plays an essential role in physiological processes such as embryo development, synaptogenesis, tissue turnover and the negative selection of T-cells, as well as in many diseases, such as cancer, and autoimmune and neurodegenerative diseases. The aim of this paper is to review the most recent data concerning the role of apoptosis in CVD, concentrating on the key apoptotic pathways in cardiomyocytes that may represent potential targets for therapeutic interventions. DATA SUMMARY: The function of apoptosis in regulating CVD has recently been extensively investigated as a possible mechanism explaining the pathophysiological significance of various forms of CVD. Despite the difficulties of studying apoptosis in cardiomyocytes, a large number of studies of cellular and animal models suggest that they have the main apoptotic pathways that are also active in other cell types. However, the role of apoptosis in human pathologies, such as heart failure, ischemic heart disease and cardiac hypertrophy is still controversial. We revised classical (TUNEL) and novel experimental approaches (knock-out and transgenic mice; high-throughput genomics and proteomics) to address the role of apoptosis in CVD, concentrating on potential targets for therapeutic intervention. CONCLUSION: Knowledge of the basic mechanisms regulating apoptosis activation and inhibition in cardiomyocytes may have important clinical and therapeutic implications.


Subject(s)
Apoptosis , Cardiovascular Diseases/pathology , Animals , Cardiovascular Diseases/genetics , Cardiovascular Diseases/therapy , Humans , In Situ Nick-End Labeling , Mice , Mice, Transgenic , Muscle Cells/pathology , Myocardium/pathology
18.
Chem Res Toxicol ; 14(9): 1296-305, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11559046

ABSTRACT

Oxidation of 6-nitrodopamine (1) and 6-nitronorepinephrine (2), as well as of the model compounds 4-nitrocatechol and 4-methyl-5-nitrocatechol, with horseradish peroxidase (HRP)/H(2)O(2), lactoperoxidase (LPO)/H(2)O(2), Fe(2+)/H(2)O(2), Fe(2+)-EDTA/H(2)O(2) (Fenton reagent), HRP or Fe(2+)/EDTA in combination with D-glucose-glucose oxidase, or Fe(2+)/O(2), resulted in the smooth formation of yellowish-brown pigments positive to the Griess assay. In the case of 1, formation of the Griess positive pigment (GPP-1) promoted by HRP/H(2)O(2) proceeded through the intermediacy of two main dimeric species that could be isolated and identified as 3 and the isomer 4, featuring the 4-nitro-6,7-dihydroxyindole system linked to a unit of 1 through ether bonds. Spectroscopic (FAB-MS, (1)H NMR) and chemical analysis of GPP-1 indicated a mixture of oligomeric species related to 3 and 4 in which oxidative modification of the nitrocatechol moiety of 1 led to the generation of reactive nitro groups supposedly linked to sp(3) hybridized carbons. In the pH range 3-6, GPP-1 induced concentration- and pH-dependent nitrosation of 2,3-diaminonaphthalene, but very poor (up to 2%) nitration of 600 microM tyrosine. At pH 7.4, 1 exerted significant toxicity to PC12 cells, while GPP-1 proved virtually innocuous. By contrast, when assayed on Lactobacillus bulgaricus cells at pH 3.5, 1 was inactive whereas GGP-1 caused about 70% inhibition of cell growth. Overall, these results hint at novel pH-dependent mechanisms of nitrocatecholamine-induced cytotoxicity of possible relevance to ischemia- or inflammation-induced catecholaminergic neuron damage.


Subject(s)
Acidosis/physiopathology , Catecholamines/toxicity , Dopamine/analogs & derivatives , Dopamine/chemistry , Nitric Oxide/chemistry , Norepinephrine/analogs & derivatives , Norepinephrine/chemistry , Oxidative Stress , Cell Division/drug effects , Ethylenediamines , Free Radical Scavengers/chemistry , Hydrogen Peroxide/chemistry , Hydrogen-Ion Concentration , Kinetics , Lactobacillus/drug effects , Lactobacillus/physiology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Oxidants/chemistry , Oxidation-Reduction , Signal Transduction , Structure-Activity Relationship , Sulfanilamides
19.
Biochem Biophys Res Commun ; 285(5): 1280-9, 2001 Aug 03.
Article in English | MEDLINE | ID: mdl-11478796

ABSTRACT

Taking advantage of the DNA array screening technology, we analysed the effect of sodium butyrate on mRNA transcription in human HT29 colon adenocarcinoma cells. Out of 588 mRNA species analysed, only 119 resulted expressed. Among these, 60 exhibited a variable degree of modulation after butyrate treatment. Genes linked to the cell growth, apoptosis and oxidative metabolism appeared the most significantly affected. Furthermore, many of the differentially expressed genes are transcription factors and this may account for the variability of the biological effects of butyrate. The pattern of butyrate-affected genes may represent a reference in further analyses of gene expression of intestinal cells and tissues.


Subject(s)
Adenocarcinoma/drug therapy , Butyrates/pharmacology , Colonic Neoplasms/drug therapy , Transcription, Genetic/drug effects , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Apoptosis/genetics , Cell Cycle/drug effects , Cell Differentiation/drug effects , Cell Division/drug effects , Cell Division/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/metabolism , Gene Expression/drug effects , Gene Expression Profiling , HT29 Cells , Humans , Oligonucleotide Array Sequence Analysis , Oxidation-Reduction , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factors/genetics , Transcription Factors/metabolism
20.
Lett Appl Microbiol ; 33(1): 61-4, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11442817

ABSTRACT

AIMS: The metabolic characterization and pathogenicity of vibrios isolated from seafood were studied. METHODS AND RESULTS: Strains of halophilic vibrios, grown in the presence of 0.5% glucose, induced high medium acidification and were non-culturable after 24 h, while moderately acidifying strains were culturable, produced cytotoxins, and remained lethal when inoculated intraperitoneally in mice. Highly acidifying strains failed to elicit pathogenicity in vivo and in vitro. CONCLUSION: The high acidification of the medium and the self-killing activity of NCVs might be considered a significant phenotypic marker of virulence and/or cytotoxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: We suggest the medium acidification test as possible screening method for pathogenic NCVs in food microbiology.


Subject(s)
Vibrio/metabolism , Vibrio/pathogenicity , Animals , Culture Media , Fermentation , Glucose/metabolism , Hydrogen-Ion Concentration , Mice , Seafood/microbiology , Vibrio/growth & development , Vibrio Infections/microbiology , Virulence
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