Publications by authors named "Mario Felice Tecce"

21 Publications

  • Page 1 of 1

NIR multiphoton ablation of cancer cells, fluorescence quenching and cellular uptake of dansyl-glutathione-coated gold nanoparticles.

Sci Rep 2020 07 9;10(1):11380. Epub 2020 Jul 9.

Department of Chemistry and Biology "Adolfo Zambelli", University of Salerno, Via Giovanni Paolo II, 84084, Fisciano, SA, Italy.

Theranostics based on two-photon excitation of therapeutics in the NIR region is an emerging and powerful tool in cancer therapy since this radiation deeply penetrates healthy biological tissues and produces selective cell death. Aggregates of gold nanoparticles coated with glutathione corona functionalized with the dansyl chromophore (a-DG-AuNPs) were synthesized and found efficient nanodevice for applications in photothermal therapy (PTT). Actually the nanoparticle aggregation enhances the quenching of radiative excitation and the consequent conversion into heat. The a-DG-AuNPs are readily internalized in Hep G2 where the chromophore acts as both antenna and transducer of the NIR radiation under two-photons excitation, determining efficient cell ablation via photothermal effect.
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http://dx.doi.org/10.1038/s41598-020-68397-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347844PMC
July 2020

NMR-based metabolomic profile of hypercholesterolemic human sera: Relationship with in vitro gene expression?

PLoS One 2020 16;15(4):e0231506. Epub 2020 Apr 16.

Department of Pharmacy, University of Salerno, Fisciano, Italy.

Hypercholesterolaemia is considered an important cause of atherosclerotic cardiovascular disease. In a previous investigation, we demonstrated that cultured hepatoma cells treated with hypercholesterolaemic sera compared with cells treated with normocholesterolaemic sera show overexpression of mRNAs related to mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2). In the present work, using an NMR metabolomic analysis, we demonstrate that the hypercholesterolaemic blood sera previously used to treat cultured hepatoma cells are characterized by a metabolomic profile that is significantly different from the normocholesterolaemic sera. Acetate, acetone, 2-hydroxybutyrate, cysteine, valine, and glutamine are the metabolites distinguishing the two groups. Abnormalities in the concentrations of these metabolites reflect alterations in energy-related pathways, such as pantothenate and CoA biosynthesis, pyruvate, glycolysis/gluconeogenesis, the citrate cycle, and ketone bodies. Regarding ketone bodies, the pathway is regulated by HMGCS2; therefore, serum samples previously found to be able to increase HMGCS2 mRNA levels in cultured cells also contain higher amounts of the metabolites of its encoded enzyme protein product.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231506PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162471PMC
July 2020

High glucose concentration produces a short-term increase in pERK1/2 and p85 proteins, having a direct angiogenetic effect by an action similar to VEGF.

Acta Diabetol 2020 Aug 4;57(8):947-958. Epub 2020 Mar 4.

Department of Medicine and Health Science "V. Tiberio", University of Molise, Campobasso, Italy.

Aims: Excessive glucose serum concentration, endothelial dysfunction and microangiopathy are key features of diabetes mellitus, being both diagnostic parameters and pathogenetic mechanisms. Vascular endothelial growth factor (VEGF) is importantly implicated in the physiology and pathology of blood vessels, including diabetic vascular damage.

Methods: These factors certainly affect endothelial cells, and to evaluate mechanisms involved, we took advantage of telomerase-immortalized human microvascular endothelial (TIME) cells. TIME cells were exposed to different glucose concentrations and to VEGF treatments. Culture conditions also included the use of basement membrane extract, as an in vitro differentiation model. Cell morphology was then evaluated in the different conditions, and cellular proteins were extracted to analyze specific protein products by Western blot.

Results: High glucose concentrations and VEGF did substantially affect neither morphology nor growth of cultured TIME cells, while both considerably increased differentiation into "capillary-like" structures when cells were cultured on basement membrane extract.

Conclusions: Under these conditions, high glucose concentration and VEGF also produced a short-term increase in pERK1/2 and p85 proteins, while total and phosphorylated AKT were not affected. These data suggest a direct angiogenetic effect of glucose, affecting intracellular transduction mechanisms with an action similar to that of VEGF. This effect on endothelial cell proliferation and differentiation could be part of pathogenetic mechanisms producing diabetic microvascular alterations.
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http://dx.doi.org/10.1007/s00592-020-01501-zDOI Listing
August 2020

Short Exposures to an Extremely Low-Frequency Magnetic Field (ELF MF) Enhance Protein but not mRNA Alkaline Phosphatase Expression in Human Osteosarcoma Cells.

Open Biochem J 2018 17;12:65-77. Epub 2018 Apr 17.

Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.

Background: Among electromagnetic fields treatments used in orthopedics, extremely low-frequency magnetic fields (ELF MF) need more detailed information about the molecular mechanisms of their effects and exposure conditions.

Objective: Evaluation of the effects of an ELF MF exposure system, recently introduced among current clinical treatments for fracture healing and other bone diseases, on Alkaline Phosphatase (ALP) activity and expression in a human osteosarcoma cell line (SaOS-2), as marker typically associated to osteogenesis and bone tissue regeneration.

Method: Cells were exposed to the ELF MF physical stimulus (75 Hz, 1.5 mT) for 1h. Cell viability, enzymatic activity, protein and mRNA expression of alkaline phosphatase were then measured at different times after exposure (0, 4 and 24 h).

Results: Data demonstrate that this signal is active on an osteogenic process already one hour after exposure. Treatment was, in fact, capable, even after an exposure shorter than those commonly used in clinical applications, to significantly up-regulate alkaline phosphatase enzymatic activity. This regulation is produced essentially through an increase of ALP protein level, without changes of its mRNA concentration, while assessed magnetic field did not affect cell growth and viability and did not produce temperature variations.

Conclusion: Tested low-frequency magnetic field affects cellular ALP expression with a posttranslational mechanism, without the involvement of regulations at gene transcription and mRNA level. This molecular effect is likely produced even within treated tissues during therapies with this signal and may be implicated in the induction of observed effects in treated patients.
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http://dx.doi.org/10.2174/1874091X01812010065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906974PMC
April 2018

Involvement of nutrients and nutritional mediators in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene expression.

J Cell Physiol 2018 04 28;233(4):3306-3314. Epub 2017 Sep 28.

Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS2) catalyses the first step of ketogenesis and is critical in various metabolic conditions. Several nutrient molecules were able to differentially modulate HMGCS2 expression levels. Docosahexaenoic acid (DHA, C22:6, n-3), eicosapentaenoic acid (EPA, C20:5, n-3), arachidonic acid (AA, C20:4, n-6), and glucose increased HMGCS2 mRNA and protein levels in HepG2 hepatoma cells, while fructose decreased them. The effect of n-6 AA resulted significantly higher than that of n-3 PUFA, but when combined all these molecules were far less efficient. Insulin reduced HMGCS2 mRNA and protein levels in HepG2 cells, even when treated with PUFA and monosaccharides. Several nuclear receptors and transcription factors are involved in HMGCS2 expression regulation. While peroxysome proliferator activated receptor α (PPAR-α) agonist WY14643 increased HMGCS2 expression, this treatment was unable to affect PUFA-mediated regulation of HMGCS2 expression. Forkhead box O1 (FoxO1) inhibitor AS1842856 reduced HMGCS2 expression and suppressed induction promoted by fatty acids. Cells treatment with liver X receptor alpha (LXRα) agonist T0901317 reduced HMGCS2 mRNA, indicating a role for this transcription factor as suppressor of HMGCS2 gene. Previous observations already indicated HMGCS2 expression as possible nutrition status reference: our results show that several nutrients as well as specific nutritional related hormonal conditions are able to affect significantly HMGCS2 gene expression, indicating a relevant role for PUFA, which are mostly derived from nutritional intake. These insights into mechanisms of its regulation, specifically through nutrients commonly associated with disease risk, indicate HMGCS2 expression as possible reference marker of metabolic and nutritional status.
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http://dx.doi.org/10.1002/jcp.26177DOI Listing
April 2018

Role of Viral miRNAs and Epigenetic Modifications in Epstein-Barr Virus-Associated Gastric Carcinogenesis.

Oxid Med Cell Longev 2016 10;2016:6021934. Epub 2016 Feb 10.

Epidemiology Unit, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.

MicroRNAs are short (21-23 nucleotides), noncoding RNAs that typically silence posttranscriptional gene expression through interaction with target messenger RNAs. Currently, miRNAs have been identified in almost all studied multicellular eukaryotes in the plant and animal kingdoms. Additionally, recent studies reported that miRNAs can also be encoded by certain single-cell eukaryotes and by viruses. The vast majority of viral miRNAs are encoded by the herpesviruses family. These DNA viruses including Epstein-Barr virus encode their own miRNAs and/or manipulate the expression of cellular miRNAs to facilitate respective infection cycles. Modulation of the control pathways of miRNAs expression is often involved in the promotion of tumorigenesis through a specific cascade of transduction signals. Notably, latent infection with Epstein-Barr virus is considered liable of causing several types of malignancies, including the majority of gastric carcinoma cases detected worldwide. In this review, we describe the role of the Epstein-Barr virus in gastric carcinogenesis, summarizing the functions of the Epstein-Barr virus-encoded viral proteins and related epigenetic alterations as well as the roles of Epstein-Barr virus-encoded and virally modulated cellular miRNAs.
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http://dx.doi.org/10.1155/2016/6021934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764750PMC
December 2016

Role of Sex Hormones in the Development and Progression of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Int J Endocrinol 2015 27;2015:854530. Epub 2015 Sep 27.

Epidemiology Unit, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.

Infection with hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC) in developed countries. Epidemiological reports indicate that the incidence of HBV-related HCC is higher in males and postmenopausal females than other females. Increasing evidence suggests that sex hormones such as androgens and estrogens play an important role in the progression of an HBV infection and in the development of HBV-related HCC. While androgen is supposed to stimulate the androgen signaling pathway and cooperate to the increased transcription and replication of HBV genes, estrogen may play a protecting role against the progression of HBV infections and in the development of HBV-related HCC through decreasing HBV RNA transcription and inflammatory cytokines levels. Additionally, sex hormones can also affect HBV-related hepatocarcinogenesis by inducing epigenetic changes such as the regulation of mRNA levels by microRNAs (miRNAs), DNA methylation, and histone modification in liver tissue. This review describes the molecular mechanisms underlying the gender disparity in HBV-related HCC with the aim of improving the understanding of key factors underneath the sex disparity often observed in HBV infections. Furthermore, the review will propose more effective prevention strategies and treatments of HBV-derived diseases.
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http://dx.doi.org/10.1155/2015/854530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600563PMC
October 2015

Effect of Docosahexaenoic Acid on Cell Cycle Pathways in Breast Cell Lines With Different Transformation Degree.

J Cell Physiol 2016 Jun 26;231(6):1226-36. Epub 2015 Oct 26.

Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.

n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), abundant in fish, have been shown to affect development and progression of some types of cancer, including breast cancer. The aim of our study was to further analyze and clarify the effects of these nutrients on the molecular mechanisms underlying breast cancer. Following treatments with DHA we examined cell viability, death, cell cycle, and some molecular effects in breast cell lines with different transformation, phenotypic, and biochemical characteristics (MCF-10A, MCF-7, SK-BR-3, ZR-75-1). These investigations showed that DHA is able to affect cell viability, proliferation, and cell cycle progression in a different way in each assayed breast cell line. The activation of ERK1/2 and STAT3 pathways and the expression and/or activation of molecules involved in cell cycle regulation such as p21(Waf1/Cip1) and p53, are very differently regulated by DHA treatments in each cell model. DHA selectively: (i) arrests non tumoral MCF-10A breast cells in G0 /G1 cycle phase, activating p21(Waf1/Cip1) , and p53, (ii) induces to death highly transformed breast cells SK-BR-3, reducing ERK1/2 and STAT3 phosphorylation and (iii) only slightly affects each analyzed process in MCF-7 breast cell line with transformation degree lower than SK-BR-3 cells. These findings suggest a more relevant inhibitory role of DHA within early development and late progression of breast cancer cell transformation and a variable effect in the other phases, depending on individual molecular properties and degree of malignancy of each clinical case.
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http://dx.doi.org/10.1002/jcp.25217DOI Listing
June 2016

Identification of Genes Selectively Regulated in Human Hepatoma Cells by Treatment With Dyslipidemic Sera and PUFAs.

J Cell Physiol 2015 Sep;230(9):2059-66

Laboratory of Molecular Nutrition, Department of Pharmacy, University of Salerno, Italy.

Serum composition is linked to metabolic diseases not only to understand their pathogenesis but also for diagnostic purposes. Quality and quantity of nutritional intake can affect disease risk and serum composition. It is then possible that diet derived serum components directly affect pathogenetic mechanisms. To identify involved factors, we evaluated the effect on gene expression of direct addition of dyslipidemic human serum samples to cultured human hepatoma cells (HepG2). Sera were selected on the basis of cholesterol level, considering this parameter as mostly linked to dietary intake. Cells were treated with 32 sera from hypercholesterolemic and normocholesterolemic subjects to identify differentially regulated mRNAs using DNA microarray analysis. We identified several mRNAs with the highest modulations in cells treated with dyslipidemic sera versus cells treated with normal sera. Since the two serum groups had variable polyunsaturated fatty acids (PUFAs) contents, selected mRNAs were further assessed for their regulation by docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (AA). Four genes resulted both affected by serum composition and PUFAs: 3-hydroxy-3-methylglutaryl-CoenzymeA synthase 2 (HMGCS2), glutathione S-transferase alpha 1 (GSTA1), liver expressed antimicrobial peptide 2 (LEAP2) and apolipoprotein M (ApoM). HMGCS2 expression appears the most relevant and was also found modulated via transcription factors peroxysome proliferator activated receptor α (PPARα) and forkhead box O1 (FoxO1). Our data indicate that expression levels of the selected mRNAs, primarily of HMGCS2, could represent a reference of nutritional intake, PUFAs effects and dyslipidemic diseases pathogenesis.
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http://dx.doi.org/10.1002/jcp.24932DOI Listing
September 2015

Binding of polyunsaturated fatty acids to LXRα and modulation of SREBP-1 interaction with a specific SCD1 promoter element.

Cell Biochem Funct 2014 Dec 29;32(8):637-46. Epub 2014 Sep 29.

Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy.

Stearoyl-CoA desaturase 1 (SCD1) is the rate limiting enzyme in unsaturated fatty acid biosynthesis. This enzyme has an important role in the regulation of hepatic lipogenesis and lipid oxidation, and alterations in these pathways may lead to several diseases. We examined, in HepG2 cell cultures, the mechanism of SCD1 regulation considering the involvement of two transcription factors: liver X receptor alpha (LXRα) and sterol regulatory element-binding protein-1 (SREBP-1), also investigating the effect of dietary polyunsaturated fatty acids (PUFAs) on this process. The analysis of SCD1 promoter allowed to identify a functional SREBP-1 binding site (SRE 1). LXRα activation increased SCD1 protein level through upregulation of SREBP-1 and its consequent binding to SRE 1 sequence. Polyunsaturated docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) and arachidonic acid (AA, C20:4) were able to reduce SREBP-1 binding to SCD1 promoter, while saturated stearic acid (SA, C18:0) did not give any effect. Surface plasmon resonance analysis showed a direct binding of DHA, EPA and AA to LXRα. These data indicate a direct inhibitory interaction of PUFAs with LXRα, a consequent reduction of SREBP-1 and of its binding to SCD1 promoter. This information provides a mechanism to explain the regulation of lipogenic pathways induced by PUFAs.
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http://dx.doi.org/10.1002/cbf.3067DOI Listing
December 2014

Metabolic syndrome, insulin resistance, circadian disruption, antioxidants and pancreatic carcinoma: an overview.

J Gastrointestin Liver Dis 2014 Mar;23(1):73-7

Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS - Naples, Italy.

The incidence and number of deaths caused by pancreatic tumours have been gradually rising, while the incidence and mortality of other common cancers have been declining. Risk factors for this malignant disease include cigarette smoking, family history of chronic pancreatitis, advancing age, male sex, diabetes mellitus, obesity, non-0 blood group, a high-fat diet, alcohol consumption and possibly Helicobacter pylori and hepatitis B virus infections. Metabolic diseases have become the leading cause of death in many countries. Our paper serves as a focused and updated discussion about the development of novel preventive strategies for this deadly disease.
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March 2014

Effect of low frequency (LF) electric fields on gene expression of a bone human cell line.

Electromagn Biol Med 2014 Dec 26;33(4):289-95. Epub 2013 Aug 26.

Department of Pharmacy and.

We evaluated the effects, on cultured human SaOS-2 cells, of exposures to the low frequency (LF) electric signal (60 kHz sinusoidal wave, 24.5 V peak-to-peak voltage, amplitude modulated by a 12.5 Hz square wave, 50% duty cycle) from an apparatus of current clinical use in bone diseases requiring regenerating processes. Cells in flasks were exposed to a capacitively coupled electric field giving electric current density in the sample of 4 µA/cm(2). The whole expressed cellular mRNAs were systematically analyzed by "DNA microchips" technology to identify all individual species quantitatively affected by field exposure. Comparisons were made between RNA samples from exposed and control sham-exposed cells. Results indicated that immediately and 4 h after exposure there were almost no differentially modulated mRNA species. However, samples obtained at 24 h after exposure showed a small number of limitedly differential signals (7 down-regulated and 3 up-regulated with a cut-off value of ±1.5; 38 and 11, respectively, with a cut-off value of ±1.3), which included mostly mRNA encoding transcription factors and DNA binding proteins. Nevertheless, in identical experimental conditions, we previously demonstrated enzymatic changes of alkaline phosphatase occurring immediately after exposure and declining in a few hours. Therefore, since enzymatic changes occur before those observed at gene regulation level, it is conceivable that only earlier effects are directly due the treatment and then these effects are later able to affect gene expression only indirectly.
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http://dx.doi.org/10.3109/15368378.2013.822387DOI Listing
December 2014

Efficacy and tolerability of vinorelbine in the cancer therapy.

Curr Drug Saf 2011 Jul;6(3):185-93

Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Via Ponte don Melillo, 84084 Fisciano-SA, Italy.

Vinorelbine (VRN) is one of the most representative compounds of its class: the vinca alkaloids. VRN interferes with microtubule assembly. VRN shows a better therapeutic index than the parent compound vincristine and vinblastine probably because of its higher affinity for mitotic microtubules. VNR high affinity for mitotic microtubules causes a high clinical efficacy for the treatment of non-small cell lung cancer (NSCLC) and for breast cancer (BC), together with a good tolerability at therapeutically effective doses. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. Unlike other vinca alkaloids, the catharanthine unit is the site of structural modification for VRN. The antitumor activity of VNR is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, VNR may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca²⁺-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis. The VNR is also characterized by improved hematologic tolerance and less neurotoxicity compared to parent compound. The aim of this review is 1) to explore the efficacy and tolerability of VNR in cancer therapy and 2) to examine the more recent approaches to improve the efficacy and tolerability of VNR in cancer therapy.
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http://dx.doi.org/10.2174/157488611797579302DOI Listing
July 2011

Selective action of human sera differing in fatty acids and cholesterol content on in vitro gene expression.

J Cell Biochem 2012 Mar;113(3):815-23

Department of Pharmaceutical and Biomedical Sciences, University of Salerno, via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy.

Serum constituents might directly affect metabolic diseases pathogenesis and are commonly used as diagnostic tool. The aim of this study was to investigate the human serum effect on in vitro gene expression, related to nutrients action and involved in lipid metabolism. In detail, 40 human sera were firstly analyzed in fatty acids profile by gas-chromatography. Then samples were tested through direct addition within culture medium on Hep G2 human hepatoma cells, comparing samples from hypercholesterolemic (average 273 mg/dl) versus normocholesterolemic male subjects (average 155 mg/dl), since this condition is a relevant disease risk factor and is typically consequent to nutritional style. Hypercholesterolemic sera produced a 0.4-fold reduction of sterol regulatory element binding protein 1c (SREBP-1c) mRNA (P < 0.05) and a 1.5-fold increase of UDP-glucuronosyltransferase 1A1 (UGT1A1) mRNA (P < 0.01). Samples with higher concentrations of n-6 fatty acids produced a higher expression of UGT1A1 mRNA. Total fatty acids [docosahexaenoic, eicosopentanoic, arachidonic, linolenic, and linoleic acid (DHA, EPA, AA, LNA, and LA, respectively)] in each serum resulted roughly inverse with trend of SREBP-1c mRNA expression. Serum AA, LA, and trans fatty acids were more abundant in hypercholesterolemic subjects (P < 0.01) while DHA as quota of detected fatty acids was significantly higher in normocholesterolemic subjects (P < 0.05). While it is not possible to indicate which component was responsible for the observed gene modulations, our data indicate that sera differing in lipid profiles, mainly associated with dietary behavior, differentially affect gene expression known to be involved in metabolic and nutritional related conditions.
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http://dx.doi.org/10.1002/jcb.23409DOI Listing
March 2012

Duloxetine in the treatment of depression: an overview.

Cent Nerv Syst Agents Med Chem 2011 Sep;11(3):174-83

Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Fisciano (Salerno) Italy.

Depression is a disorder that can be classified in the categories of non-organic psychiatric disorders and mood disorders. Mood tone is an important psychic function involved in the adaptation to both our internal and external world. It is flexible, that is, it goes up when we are in positive and favorable conditions, but it goes down when we are in negative and unpleasant states. We can define depression as a condition when mood tone loses its flexibility, it goes down and it's no longer influenced by favorable external events. In fact, depression is characterized by changes in the way how the affected individual thinks, feels and acts. Even if this change occurs gradually, a depressed subject is not the same as before. For example, a brilliant student could be persuaded to be not able to finish his studies; an affectionate mother could start to neglect her sons; an enterprising worker could lose every interest for his activity. Moreover, a depressed person doesn't care of his aspect or of himself. The surviving instinct could leave place to the desire to stop his own life. The most evident characteristic of depression in the adulthood is a sad mood, a gloomy solitary and apathetic attitude. A depressed subject could cry also with no apparent reason, he could have difficulty falling asleep or he could wake up very early in the morning and no longer returns to sleep. Or, instead, he could sleep more than usually and he could feel tired persistently. He could lose appetite and weight, or, in some cases, he could eat much more than usually and he could gain weight. Typically, a depressed person feels himself in a extremely negative way, he could think to be hopeless and helpless and he often condemns himself for small guilty. A depressed subject is pessimistic about himself and his own future; he loses interest in all what happens around him and he gets no satisfaction from the activities that before were pleasant. Some persons can be depressed also if they don't show evident signs of depression, but they complain for physical symptoms or they abuse of alcohol or other substances. It has been estimated that in the industrialized Western world one to six persons has a depressive episode at least once during his life; at present, the incidence of depression in the general population is around 5% with clear cut prevalence in the female sex. This leads to high social costs: behind the short-term inability, we have to consider also the long term inability (it has been estimated that, in 2020, depression will represent the second most frequent cause of permanent inability) as well as the suicide risk, the proved major susceptibility of depressed subjects to various non-psychiatric pathologies and the increased rate of premature deaths of depressed individuals as compared to the general population. The present work not only evaluates the drugs used for the treatment of depression, but it focuses also on those studies that investigated the efficacy of a second generation drug: Duloxetine that has a higher selectivity of action and a better tolerability profile as compared to first generation medications. These characteristics make Duloxetine the most effective therapeutic choice to improve both psychological and somatic symptoms of depression in order to get higher rates of symptomatic remission on depressive episodes.
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http://dx.doi.org/10.2174/187152411798047807DOI Listing
September 2011

Induction of alkaline phosphatase activity by exposure of human cell lines to a low-frequency electric field from apparatuses used in clinical therapies.

Bioelectromagnetics 2011 Feb 23;32(2):113-9. Epub 2010 Nov 23.

Department of Information and Electrical Engineering, University of Salerno, Fisciano, SA, Italy.

Low-frequency (LF) electric fields (EFs) are currently used in clinical therapies of several bone diseases to increase bone regenerative processes. To identify possible molecular mechanisms involved in these processes, we evaluated the effects on cell cultures of 1 h exposures to the signal generated by an apparatus of current clinical use (frequency 60 kHz, frequency of the modulating signal 12.5 Hz, 50% duty cycle, peak-to-peak voltage 24.5 V). Two different human cell lines, bone SaOS-2 and liver HepG2, were used. Exposures significantly increased alkaline phosphatase (ALP) enzymatic activity in both cell lines. The increase was about 35% in SaOS-2 cells and about 80% in HepG2 cells and occurred in the first 4 h after exposure and decreased to almost no change by 24 h. Since ALP represents a typical marker of bone regeneration, these results represent a first molecular evidence of biological effects from 60 kHz EF exposures. The finding of similar effects in cells derived from two different tissues more likely indicates the effective operation of the mechanism in living organisms.
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http://dx.doi.org/10.1002/bem.20630DOI Listing
February 2011

Potential therapeutic effects of vitamin e and C on placental oxidative stress induced by nicotine: an in vitro evidence.

Open Biochem J 2010 Jun 24;4:77-82. Epub 2010 Jun 24.

Dipartimento di Psicologia, Universita' di Roma "La Sapienza" Via dei Marsi 78, (00185) Roma.

There have been a few studies that examined the oxidative stress effects of nicotine during pregnancy and lactation. The adverse effect of prenatal smoking exposure on human fetal development and growth has been a major public health issue. Active or passive smoking during pregnancy can result in a wide variety of adverse outcomes, including intrauterine growth retardation (IUGR), prematurity, stillbirth, and the sudden infant death syndrome. Smoking in pregnancy has also been associated with an increased risk of attention deficit and learning problems in childhood. Some studies argued that as a principal component of tobacco smoke, nicotine alone is responsible for the majority of negative reproductive outcomes. Nicotine and its major metabolite cotinine can cross the placental barrier. The level of nicotine in fetal tissues was found to be equal to or greater than the plasma nicotine level in the mothers. The oxidative stress induce by nicotine has been increasingly postulated as a major contributor to endothelial dysfunction. A large body of research has investigated the potential role of antioxidant nutrients in the prevention of endothelial dysfunction in women. Therefore, the present study was undertaken to assess the potential benefit of antioxidant supplementation on markers of placental oxidative stress in an in vitro model of endothelial dysfunction induced by nicotine, since it was previously found that nicotine is able to trigger the placental secretion of stress molecules. In this regard, we evaluated the effects of vitamin C, vitamin E and N-acetylcysteine (NAC), alone or in combination, in placental villi culture after exposure to nicotine. The effect of antioxidant nutrients on trophoblast cells proliferation and vitality was also evaluated. The results obtained suggest that in a patho-physiological condition, such as endothelial dysfunction induced by nicotine, the deleterious effect of reactive oxygen species may be counteracted by an antioxidant therapy, and there is the need to investigate the optimum dosing and timing of antioxidants administration, since an inappropriate antioxidant treatment in pregnant women may have deleterious consequences, reducing placental cells proliferation until to cell death.
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http://dx.doi.org/10.2174/1874091X01004010077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911599PMC
June 2010

Selective regulation of UGT1A1 and SREBP-1c mRNA expression by docosahexaenoic, eicosapentaenoic, and arachidonic acids.

J Cell Physiol 2011 Jan;226(1):187-93

Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Italy.

We evaluated, in human cell line HepG2, the action of individual dietary polyunsaturated fatty acids (PUFAs) on the expression of several lipid metabolism genes. The effects of docosahexaenoic acid, 22:6, n-3 (DHA), eicosapentaenoic acid, 20:5, n-3 (EPA), and arachidonic acid, 20:4, n-6 (AA) were studied alone and with vitamin E (Vit.E). DHA, EPA, and AA down-regulated mRNAs and encoded proteins of stearoyl-CoA desaturase (SCD) and sterol regulatory element binding protein (SREBP-1c), two major factors involved in unsaturated fatty acids synthesis. DHA affected SREBP-1c mRNA less markedly than EPA and AA. Vit.E did not affect these products, both when individually added or together with fatty acids. The expression of UDP-glucuronosyl transferase 1A1 (UGT1A1) mRNA, an enzyme of phase II drug metabolism with relevant actions within lipid metabolism, resulted also differentially regulated. DHA did not essentially reduce UGT1A1 mRNA expression while EPA and AA produced a considerable decrease. Nevertheless, when these PUFAs were combined with Vit.E, which by itself did not produce any effect, the result was a reduction of UGT1A1 mRNA with DHA, an increase reverting to basal level with EPA and no variation with AA. Observed regulations did not result to be mediated by peroxisome proliferator-activated receptor (PPAR). Our data indicate that major dietary PUFAs and Vit.E are differentially and selectively able to affect the expression of genes involved in lipid metabolism. The different actions of these slightly different molecules could be associated with their physiological role as relevant nutrient molecules.
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http://dx.doi.org/10.1002/jcp.22323DOI Listing
January 2011

Therapeutic targeting of the stem cell niche in experimental hindlimb ischemia.

Nat Clin Pract Cardiovasc Med 2008 Sep 15;5(9):571-9. Epub 2008 Apr 15.

Department of General Pathology, 1st School of Medicine, II University of Naples, Naples, Italy.

Background: The custom microenvironment 'vascular niche' is a potential therapeutic target for several pathophysiological conditions. Osteoblasts regulate the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor can increase the number of cells mobilized into the bloodstream.

Methods: C57Bl/6 mice were randomly assigned treatment with granulocyte-colony stimulating factor (G-CSF), PTH, G-CSF plus PTH or saline. All mice underwent hindlimb ischemia. Blood flow was measured by laser Doppler imaging. Indices of capillary activity were determined by electron microscopy in muscle tissue. CD34(+) and Ki67(+) cells were detected and evaluated by immunofluorescence, apoptosis by TUNEL, surface antigen and endothelial progenitor cells by fluorescence-activated cell sorting analysis, and vascular endothelial growth factor-164 and angiopoietin-1 expression by reverse-transcriptase polymerase chain reaction. Frozen bone marrow sections were stained for antigen-specific B cells and fibronectin and analyzed by confocal laser scanning microscopy.

Results: Following mobilization induced by G-CSF treatment, mice also treated with PTH showed increases in blood flow, capillary density, nitrite/nitrate release, angiogenic factors and circulating progenitor cells, as well as reduced apoptosis, fibrosis, oxidative stress and inflammation in ischemic muscles. Furthermore, hematopoietic antigen-specific B cells in the bone marrow were also increased by G-CSF alone and in combination with PTH.

Conclusions: PTH might increase the efficiency of hematopoietic stem-cell-based therapy in a recognized model of peripheral ischemia. Our translational experimental therapeutic targeting of the vascular niche points to novel clinical targets for the hematopoietic stem-cell treatment of ischemic vascular diseases.
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http://dx.doi.org/10.1038/ncpcardio1214DOI Listing
September 2008

Higher farnesyl diphosphate synthase activity in human colorectal cancer inhibition of cellular apoptosis.

Oncology 2004 ;67(5-6):351-8

Laboratory of Biochemistry, National Institute for Digestive Diseases, Castellana Grotte, Bari, Italy.

Objective: Farnesyl diphosphate synthase (FPPs) produces FPP which is considered a branch-point intermediate in the synthesis of sterols and isoprenylated cellular metabolites. In this study we investigated whether detectable FPPs activity was present in human colorectal cancer (CRC), also evaluating in vitro the role of this enzyme in the growth and apoptosis of CRC cells by using Pamidronate (PAM), a FPPs activity inhibitor.

Methods: The activity level of FPPs was determined in CRC and the normal surrounding mucosa of 50 patients by radiochemical assay. The FPPs mRNA expression was investigated in 15 of 50 patients by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). K-ras mutation was evaluated using PCR and restriction enzyme analysis. Cell growth and apoptosis, after PAM treatment, in human CRC cell line DLD-1 were measured by MTT test and DNA fragmentation, respectively.

Results: FPPs activity was detectable in human CRC. FPPs activity and its mRNA were significantly more abundant in cancer samples than in normal mucosa. In vitro PAM resulted in a significant reduction of cell growth and also gave rise to a marked proapoptotic effect.

Conclusions: This study provides the first evidence of the presence of FPPs activity in human CRC. Moreover, FPPs enzyme was found to play a significant role in colon cancer proliferation.
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http://dx.doi.org/10.1159/000082918DOI Listing
February 2005

Antioxidant effect of hydroxytyrosol (DPE) and Mn2+ in liver of cadmium-intoxicated rats.

Comp Biochem Physiol C Toxicol Pharmacol 2002 Dec;133(4):625-32

Department of Pharmaco-Biology, University of Bari, Str Prov Per Casamassima, Km 3, 70010 Valenzano,(Ba), Italy.

Liver TBARS formation in cadmium-intoxicated rats was completely reduced by administering a low amount of MnCl(2) (2 mg/kg b.w.) 1 h before intoxication. A similar antioxidant effect was first shown by hydroxytyrosol (2-(3,4-dihydroxyphenyl)ethanol, (DPE), a phenolic compound present in olive oil, given twice to rats (9 mg/kg b.w.) after cadmium administration. The antioxidant properties shown in vivo by both Mn(2+) and DPE were also active in vitro when rat liver microsomes were subjected to lipid peroxidation by cadmium or other prooxidant systems. The increase in liver glutathione concentrations occurring in cadmium-intoxicated rats, was also found, for the first time, 24 h after MnCl(2) administration. Unlike cadmium intoxication, which caused a higher formation of both glutathione and TBARS, Mn(2+) induced glutathione synthesis without any TBARS formation. The same situation was also observed when cadmium plus Mn(2+) or cadmium plus DPE was given to rats. Our data show that: (a). both DPE and low Mn(2+) concentrations may have an antioxidant effect in the livers of cadmium-intoxicated rats and (b). Mn(2+), like cadmium, induces liver glutathione synthesis and this effect is probably independent of TBARS formation.
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http://dx.doi.org/10.1016/s1532-0456(02)00180-1DOI Listing
December 2002
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