Publications by authors named "Francesco Paolo Fanizzi"

66 Publications

Progress towards Sustainable Control of subsp. in Olive Groves of Salento (Apulia, Italy).

Pathogens 2021 May 29;10(6). Epub 2021 May 29.

Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Monteroni-Lecce, Italy.

subsp. is the causal agent of "olive quick decline syndrome" in Salento (Apulia, Italy). On April 2015, we started interdisciplinary studies to provide a sustainable control strategy for this pathogen that threatens the multi-millennial olive agroecosystem of Salento. Confocal laser scanning microscopy and fluorescence quantification showed that a zinc-copper-citric acid biocomplex-Dentamet-reached the olive xylem tissue either after the spraying of the canopy or injection into the trunk, demonstrating its effective systemicity. The biocomplex showed in vitro bactericidal activity towards all subspecies. A mid-term evaluation of the control strategy performed in some olive groves of Salento indicated that this biocomplex significantly reduced both the symptoms and subsp. cell concentration within the leaves of the local cultivars Ogliarola salentina and Cellina di Nardò. The treated trees started again to yield. A H-NMR metabolomic approach revealed, upon the treatments, a consistent increase in malic acid and γ-aminobutyrate for Ogliarola salentina and Cellina di Nardò trees, respectively. A novel endotherapy technique allowed injection of Dentamet at low pressure directly into the vascular system of the tree and is currently under study for the promotion of resprouting in severely attacked trees. There are currently more than 700 ha of olive groves in Salento where this strategy is being applied to control . subsp. . These results collectively demonstrate an efficient, simple, low-cost, and environmentally sustainable strategy to control this pathogen in Salento.
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http://dx.doi.org/10.3390/pathogens10060668DOI Listing
May 2021

H-NMR Profiling Shows as Specific Constituents Strongly Affect the International EVOO Blends Characteristics: The Case of the Italian Oil.

Molecules 2021 Apr 13;26(8). Epub 2021 Apr 13.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy.

Considering the growing number of extra virgin olive oil (EVOO) producers in the world, knowing the influence of olive oils with different geographical origins on the characteristics of the final blend becomes an interesting goal. The present work is focused on commercial organic EVOO blends obtained by mixing multiple oils from different geographical origins. These blends have been studied by H-NMR spectroscopy supported by multivariate statistical analysis. Specific characteristics of commercial organic EVOO blends originated by mixing oils from Italy, Tunisia, Portugal, Spain, and Greece were found to be associated with the increasing content of the Italian component. A linear progression of the metabolic profile defined characteristics for the analysed samples-up to a plateau level-was found in relation to the content of the main constituent of the Italian oil, the monocultivar Coratina. The Italian constituent percentage appears to be correlated with the fatty acids (oleic) and the polyphenols (tyrosol, hydroxytyrosol, and derivatives) content as major and minor components respectively. These results, which highlight important economic aspects, also show the utility of H-NMR associated with chemometric analysis as a powerful tool in this field. Mixing oils of different national origins, to obtain blends with specific characteristics, could be profitably controlled by this methodology.
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http://dx.doi.org/10.3390/molecules26082233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069555PMC
April 2021

First Insight into Nutraceutical Properties of Local Salento Varieties: NMR-Based Metabolomic Approach.

Int J Environ Res Public Health 2021 04 12;18(8). Epub 2021 Apr 12.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy.

Background: Plants of genus are known for their therapeutic and nutraceutical properties determined by a wealth of phytochemical substances contained in the whole plant. The aim of this paper was to characterize the metabolic profiles of local Salento chicory ( L.) varieties ("Bianca", "Galatina", "Leccese", and "Otranto") in order to describe their metabolites composition together with possible bioactivity and health beneficial properties.

Methods: The investigation was performed by H-NMR spectroscopy and Multivariate Analysis (MVA), by which the metabolic profiles of the samples were easily obtained and compared.

Results: The supervised Partial Least Squares Discriminant Analysis (PLS-DA) analysis showed as "Bianca" and "Galatina" samples grouped together separated by "Leccese" and "Otranto" varieties. A different content of free amino acids and organic acids was observed among the varieties. In particular a high content of cichoric and monocaffeoyl tartaric acid was observed for the "Leccese" variety. The presence of secondary metabolites adds significant interest in the investigation of , as this vegetable may benefit human health when incorporated into the diet.

Conclusions: The H-NMR (Nuclear Magnetic Resonance Spectroscopy) based characterization of Salento chicory varieties allowed us to determine the potential usefulness and nutraceutical properties of the product, also providing a method to guarantee its authenticity on a molecular scale.
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http://dx.doi.org/10.3390/ijerph18084057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069254PMC
April 2021

Olive Cultivars Susceptible or Tolerant to Subsp. Exhibit Mid-Term Different Metabolomes upon Natural Infection or a Curative Treatment.

Plants (Basel) 2021 Apr 15;10(4). Epub 2021 Apr 15.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy.

subsp. is a bacterial phytopathogen associated with the "olive quick decline syndrome" (OQDS) causing severe economic losses to olive groves in Salento area (Apulia, Italy). In a previous work, we analyzed by H-NMR the metabolic pattern of naturally infected Ogliarola salentina and Cellina di Nardò susceptible cultivars untreated and treated with a zinc-copper citric acid biocomplex and we observed the treatment related variation of the disease biomarker quinic acid. In this study, we focused also on the Leccino cultivar, known to exhibit tolerance to the disease progression. The H-NMR-based metabolomic approach was applied with the aim to characterize the overall metabolism of tolerant Leccino in comparison with the susceptible cultivars Ogliarola salentina and Cellina di Nardò under periodic mid-term treatment. In particular, we studied the leaf extract molecular patterns of naturally infected trees untreated and treated with the biocomplex. The metabolic Leccino profiles were analyzed for the first time and compared with those exhibited by the susceptible Cellina di Nardò and Ogliarola salentina cultivars. The study highlighted a specificity in the metabolic response of the tolerant Leccino compared to susceptible cultivars. These differences provide useful information to describe the defensive mechanisms underlying the change of metabolites as a response to the infection, and the occurrence of different levels of disease, season and treatment effects for olive cultivars.
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http://dx.doi.org/10.3390/plants10040772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103516PMC
April 2021

DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer.

Cancer Res 2021 Jun 24;81(11):2861-2873. Epub 2021 Mar 24.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies. SIGNIFICANCE: This study uncovers a link between a central effector of DNA damage response, CHK2, and cellular metabolism, revealing potential therapeutic strategies for targeting hepatocellular carcinoma.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3134DOI Listing
June 2021

H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth.

Sci Rep 2021 Jan 13;11(1):1259. Epub 2021 Jan 13.

Interdisciplinary Department of Medicine, University of Bari School of Medicine, Piazza G. Cesare, 11, 70124, Bari, Italy.

Hepatocellular carcinoma (HCC) is nowadays the sixth cause of tumour-related deceases worldwide, estimated to become the third in Western countries by 2030. New drugs for HCC treatment still have many adverse effects. Several lines of evidence indicate that plant metabolites offer concrete opportunities for developing new therapeutic strategies for many diseases, including cancer. We previously reported that ethyl acetate extract of a spontaneous edible plant harvested in Apulia, Crithmum maritimum, significantly inhibited cell growth in HCC cells. By H-NMR spectroscopy, here we show that Crithmum maritimum ethyl acetate extract counteracts the Warburg effect, by reducing intracellular lactate, inhibits protein anabolism, by decreasing amino acid level, and affects membrane biosynthesis by lowering choline and phosphocholine. Also, we observed an effect on lipid homeostasis, with a reduction in triglycerides, cholesterol, monounsaturated fatty acids (MUFA), and diunsaturated fatty acids (DUFA), and an increase in polyunsaturated fatty acids (PUFA). Taken together, these data demonstrate that Crithmum maritimum-induced cytostasis is exerted through a multi-effect action, targeting key metabolic processes in HCC cells. Overall, our findings highlight the role of Crithmum maritimum as a promising tool for the prevention and the improvement of the therapeutic options for HCC and other types of tumours.
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http://dx.doi.org/10.1038/s41598-020-78867-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806899PMC
January 2021

H NMR Spectroscopy to Characterize Italian Extra Virgin Olive Oil Blends, Using Statistical Models and Databases Based on Monocultivar Reference Oils.

Foods 2020 Dec 3;9(12). Epub 2020 Dec 3.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy.

During the last few years, the global demand for extra virgin olive oil (EVOO) is increased. Olive oil represents a significant percentage of world fat consumption determining an important development of its market. In this context, the problems related to counterfeiting and product fraud is becoming extremely relevant. Thus, the quality and authenticity control of EVOOs is nowadays mandatory. In this study we focused on the use of H NMR technique associated with multivariate statistical analysis to characterize Italian EVOOs commercial blends. In particular, a specific database including 126 monocultivar EVOOs reference samples, was used to characterize a total of 241 Italian EVOOs blends over four consecutive harvesting years. Moreover, the effect of the minor components (phenolic compounds) on the qualitative characterization of blended EVOOs was also evaluated. The correlation analysis of classification scores obtained using two pairwise orthogonal partial least square-discriminant analysis models (built with major and combined major-minor components NMR data) revealed that both could be profitably used to generally classify the studied Coratina containing blends.
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http://dx.doi.org/10.3390/foods9121797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761774PMC
December 2020

Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine.

Molecules 2020 Jul 31;25(15). Epub 2020 Jul 31.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, I-73100 Lecce, Italy.

A H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel nicotinamide derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC value, were investigated, with respect to the controls (K), by the H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or adenosylmethionine (SAM) limitation.
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http://dx.doi.org/10.3390/molecules25153502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435671PMC
July 2020

Soil and Leaf Ionome Heterogeneity in Subsp. -Infected, Non-Infected and Treated Olive Groves in Apulia, Italy.

Plants (Basel) 2020 Jun 17;9(6). Epub 2020 Jun 17.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, I-73100 Lecce, Italy.

subsp. is responsible for the "olive quick decline syndrome" (OQDS) in Salento (Apulia). The main epidemiological aspects of the syndrome are related to the pathogen spread and survival in the area, and to the biology of the insect vector. The assessment of the macro and microelements content (i.e., ionome) in soil and leaves could provide basic and useful information. Indeed, knowledge of host ionomic composition and the possibility of its modification could represent a potential tool for the management of diseases caused by . Therefore, soil and leaf ionomes of naturally infected, not infected, and zinc-copper-citric acid biocomplex treated trees of different areas of Apulia and the bordering Basilicata regions were compared. We observed that soil and leaf ionomic composition of olive farms growing in the pathogen-free areas north of the Salento Barletta-Andria-Trani BAT (Apulia) and Potenza PZ (Basilicata, Apulia bordering region) provinces is significantly different from that shown by the infected olive groves of the Salento areas (LE, BR, TA provinces). In particular, a higher content of zinc and copper both in soil and leaves was found in the studied northern areas in comparison to the southern areas. This finding could partly explain the absence of OQDS in those areas. In the infected Salento areas, the leaf ionomic profile resulted as being markedly different for the biocomplex treated compared to the untreated trees. A higher zinc content in leaves characterized treated with respect to untreated trees. On the other hand, among the not-infected trees, -resistant Leccino showed higher manganese content when compared with the higher pathogen sensitive Ogliarola salentina and Cellina di Nardò. According to these results, soil and olive leaf ionome could provide basic information for the epidemiologic study and possible control of subsp. in Apulia.
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http://dx.doi.org/10.3390/plants9060760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356509PMC
June 2020

Correction to: [Pt(O,O'-acac)(γ-acac)(DMS)]: Alternative Strategies to Overcome Cisplatin-Induced Side Effects and Resistance in T98G Glioma Cells.

Cell Mol Neurobiol 2021 Apr;41(3):589

Laboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology ''L. Spallanzani'', University of Pavia, via Ferrata 9, 27100, Pavia, Italy.

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http://dx.doi.org/10.1007/s10571-020-00896-1DOI Listing
April 2021

[Pt(O,O'-acac)(γ-acac)(DMS)]: Alternative Strategies to Overcome Cisplatin-Induced Side Effects and Resistance in T98G Glioma Cells.

Cell Mol Neurobiol 2021 Apr 19;41(3):563-587. Epub 2020 May 19.

Laboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology ''L. Spallanzani'', University of Pavia, via Ferrata 9, 27100, Pavia, Italy.

Cisplatin (CDDP) is one of the most effective chemotherapeutic agents, used for the treatment of diverse tumors, including neuroblastoma and glioblastoma. CDDP induces cell death through different apoptotic pathways. Despite its clinical benefits, CDDP causes several side effects and drug resistance.[Pt(O,O'-acac)(γ-acac)(DMS)], namely PtAcacDMS, a new platinum(II) complex containing two acetylacetonate (acac) and a dimethylsulphide (DMS) in the coordination sphere of metal, has been recently synthesized and showed 100 times higher cytotoxicity than CDDP. Additionally, PtAcacDMS was associated to a decreased neurotoxicity in developing rat central nervous system, also displaying great antitumor and antiangiogenic activity both in vivo and in vitro. Thus, based on the knowledge that several chemotherapeutics induce cancer cell death through an aberrant increase in [Ca], in the present in vitro study we compared CDDP and PtAcacDMS effects on apoptosis and intracellular Ca dynamics in human glioblastoma T98G cells, applying a battery of complementary techniques, i.e., flow cytometry, immunocytochemistry, electron microscopy, Western blotting, qRT-PCR, and epifluorescent Ca imaging. The results confirmed that (i) platinum compounds may induce cell death through an aberrant increase in [Ca] and (ii) PtAcacDMS exerted stronger cytotoxic effect than CDDP, associated to a larger increase in resting [Ca]. These findings corroborate the use of PtAcacDMS as a promising approach to improve Pt-based chemotherapy against gliomas, either by inducing a chemosensitization or reducing chemoresistance in cell lineages resilient to CDDP treatment.
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http://dx.doi.org/10.1007/s10571-020-00873-8DOI Listing
April 2021

H NMR Metabolic Profile of Scyphomedusa (Scyphozoa, Cnidaria) in Female Gonads and Somatic Tissues: Preliminary Results.

Molecules 2020 Feb 13;25(4). Epub 2020 Feb 13.

Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, via Monteroni, 73100 Lecce, Italy.

The Mediterranean basin is one of the regions heavily affected by jellyfish bloom phenomena, mainly due to the presence of scyphozoans, such as . The jellyfish have few natural predators, and their bodies represent an organic-rich substrate that can support rapid bacterial growth with great impact on the structure of marine food webs. In Asiatic countries, jellyfish are widely studied for their health benefits, but their nutritional and nutraceutical values still remain poorly characterized. In this study, the differences in the H NMR spectroscopy metabolic profiles of female gonads and body fractions (including umbrella and oral arms), in different sampling periods, were studied. For each body compartment both lipid and aqueous extracts were characterized and their H NMR metabolic profiles subjected to multivariate analysis. From a statistical analysis of the extracts, a higher contents of ω-3 polyunsaturated fatty acids (PUFAs), amino acid and osmolytes (homarine, betaine, taurine) with important roles in marine invertebrates were observed in female gonads, whereas umbrella and oral arms showed similar metabolic profiles. These results support a sustainable exploitation of the jellyfish for the extraction of bioactive compounds useful in nutraceutical, nutricosmetics, and functional food fields.
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http://dx.doi.org/10.3390/molecules25040806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070884PMC
February 2020

H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages.

Cancers (Basel) 2020 Jan 18;12(1). Epub 2020 Jan 18.

Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.

The application of non-targeted serum metabolomics profiling represents a noninvasive tool to identify new clinical biomarkers and to provide early diagnostic differentiation, and insight into the pathological mechanisms underlying hepatocellular carcinoma (HCC) progression. In this study, we used proton Nuclear Magnetic Resonance (H-NMR) Spectroscopy and multivariate data analysis to profile the serum metabolome of 64 HCC patients, in early (n = 28) and advanced (n = 36) disease stages. We found that H-NMR metabolomics profiling could discriminate early from advanced HCC patients with a cross-validated accuracy close to 100%. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed significant changes in serum glucose, lactate, lipids and some amino acids, such as alanine, glutamine, 1-methylhistidine, lysine and valine levels between advanced and early HCC patients. Moreover, in early HCC patients, Kaplan-Meier analysis highlighted the serum tyrosine level as a predictor for overall survival (OS). Overall, our analysis identified a set of metabolites with possible clinical and biological implication in HCC pathophysiology.
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http://dx.doi.org/10.3390/cancers12010241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016798PMC
January 2020

First Insight on the Mucus of the Annelid (Polychaeta, Sabellidae) as a Potential Prospect for Drug Discovery.

Mar Drugs 2019 Jul 5;17(7). Epub 2019 Jul 5.

Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Prov.le Lecce Monteroni, 73100 Lecce, Italy.

Many marine organisms, including invertebrates, produce mucosal matrices having different functions. Besides mechanical protection, the mucus of many invertebrates contains specific compounds to make the animal poisonous and/or distasteful or irritating. The presence of antibiotic molecules is more advantageous for some invertebrates to contrast bacterial attack. In the present study we investigated the mucus of the Mediterranean annelid species living in a gelatinous envelope made up of dense mucus. Antimicrobial lysozyme-like and antioxidant activities were investigated to highlight the potential interest of the worm mucus as a source of bioactive compounds for biotechnological applications. In order to understand which kind of compounds could be responsible for the detected activities, the mucus of was chemically characterized in terms of elemental composition, protein, lipid and carbohydrate content. Further chemical characterization was achieved by the advanced analytical technique of multinuclear and multidimensional NMR spectroscopy. NMR spectroscopy revealed the scarcity of lipids which preferentially resulted of alcoholic origin, or otherwise hydroxylate and several aminoacids (valine, leucine and alanine) in the aqueous extract in relation to the protein nature of mucus. The mucus indeed is mainly composed by water (94% ± 0.7%) whereas its dry weight is made of proteins (36% ± 2.3%) followed by lipids (2.9% ± 0.07%) and carbohydrates (2% ± 0.31%). The mucus exerted a natural antibacterial lysozyme-like activity corresponding to 1.14 mg mL of hen egg-white lysozyme and an antioxidant activity corresponding to 483.00 ± 79.22 nmolTE (Trolox equivalent)/mL sample as Trolox Equivalent Antioxidant Capacity (TEAC) and 276.26 ± 50.76 nmolTE/mL sample as Oxygen Radical Absorbance Capacity (ORAC). Therefore, our findings have potential implications due to the ongoing explosion of antibiotic resistant infections and the need to discover antibacterial agents. Additionally, the observed antioxidant activity is intriguing taking into account the need to find natural antioxidants useful for human health.
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http://dx.doi.org/10.3390/md17070396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669576PMC
July 2019

NMR-Based Metabolomics in Metal-Based Drug Research.

Molecules 2019 Jun 15;24(12). Epub 2019 Jun 15.

Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Monteroni, I-73100 Lecce, Italy.

Thanks to recent advances in analytical technologies and statistical capabilities, the application field of metabolomics has increased significantly. Currently, this approach is used to investigate biological substrates looking for metabolic profile alterations, diseases markers, and drug effects. In particular, NMR spectroscopy has shown great potential as a detection technique, mainly for the ability to detect multiple (10s to 100s) metabolites at once without separation. Only in recent years has the NMR-based metabolomic approach been extended to investigate the cell metabolic alterations induced by metal-based antitumor drug administration. As expected, these studies are mainly focused on platinum complexes, but some palladium and ruthenium compounds are also under investigation. The use of a metabolomics approach was very effective in assessing tumor response to drugs and providing insights into the mechanism of action and resistance. Therefore, metabolomics may open new perspectives into the development of metal-based drugs. In particular, it has been shown that NMR-based, in vitro metabolomics is a powerful tool for detecting variations of the cell metabolites induced by the metal drug exposure, thus offering also the possibility of identifying specific markers for in vivo monitoring of tumor responsiveness to anticancer treatments.
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http://dx.doi.org/10.3390/molecules24122240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630333PMC
June 2019

Screening of Lipidic Extract as A New Potential Source of Bioactive Compounds.

Mar Drugs 2019 May 28;17(6). Epub 2019 May 28.

Institute of Water Research (IRSA) C.N.R, 74123 Taranto, Italy.

Recent studies have shown that marine algae represent a great source of natural compounds with several properties. The lipidic extract of the seaweed (Chlorophyta, Cladophorales), one of the dominant species in the Mar Piccolo of Taranto (Mediterranean, Ionian Sea), revealed an antibacterial activity against and , common pathogens in aquaculture, suggesting its potential employment to control fish and shellfish diseases due to vibriosis and to reduce the public health hazards related to antibiotic use in aquaculture. This extract showed also an antioxidant activity, corresponding to 170.960 ± 16. mmol Trolox equivalent/g (oxygen radical absorbance capacity assay-ORAC) and to 30.554 ± 2.30 mmol Trolox equivalent/g (Trolox equivalent antioxidant capacity assay-TEAC). The chemical characterization of the extract, performed by 1D and 2D NMR spectroscopy, highlighted the presence of free, saturated (SAFAs), unsaturated (UFAs) and polyunsaturated (PUFAs) fatty acids. The high content of ω-6 and ω-3 PUFAs confirmed also by gas chromatography indicates the potentiality of this algal species in the production of fortified food. The antibacterial activity seems related to the presence of linolenic acid present at high density, while the antioxidant activity could be likely ascribable to molecules such as carotenoids and chlorophylls (characterized also by thin-layer chromatography), known for this property. The presence of polyhydroxybutyrate, a biopolymer with potentiality in the field of biodegradable bioplastics was also detected. The exploitation of for a future biotechnological application is also encouraged by the results from a first attempt of cultivating this species in an integrated multi-trophic aquaculture (IMTA) system.
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http://dx.doi.org/10.3390/md17060313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627440PMC
May 2019

NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus.

J Clin Med 2019 May 21;8(5). Epub 2019 May 21.

Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, 73100 Lecce, Italy.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a H-Nuclear Magnetic Resonance (H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.
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http://dx.doi.org/10.3390/jcm8050720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571571PMC
May 2019

CaCO as an Environmentally Friendly Renewable Material for Drug Delivery Systems: Uptake of HSA-CaCO Nanocrystals Conjugates in Cancer Cell Lines.

Materials (Basel) 2019 May 7;12(9). Epub 2019 May 7.

Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, Università del Salento & UdR INSTM di Lecce, Campus Universitario, Via Monteroni, 73100 Lecce, Italy.

Chemical and biochemical functionalization of nanoparticles (NPs) can lead to an active cellular uptake enhancing their efficacy thanks to the targeted localization in tumors. In the present study calcium carbonate nano-crystals (CCNs), stabilized by an alcohol dehydration method, were successfully modified by grafting human serum albumin (HSA) on the surface to obtain a pure protein corona. Two types of CCNs were used: naked CaCO and the (3-aminopropyl)triethoxysilane (APTES) modified CaCO-NH. The HSA conjugation with naked CCN and amino-functionalized CCN (CCN-NH) was established through the investigation of modification in size, zeta potential, and morphology by Transmission Electron Microscopy (TEM). The amount of HSA coating on the CCNs surface was assessed by spectrophotometry. Thermogravimetric analysis (TGA) and Differential scanning calorimetry (DSC) confirmed the grafting of APTES to the surface and successive adsorption of HSA. Furthermore, to evaluate the effect of protein complexation of CCNs on cellular behavior, bioavailability, and biological responses, three human model cancer cell lines, breast cancer (MCF7), cervical cancer (HeLa), and colon carcinoma (Caco-2) were selected to characterize the internalization kinetics, localization, and bio-interaction of the protein-enclosed CCNs. To monitor internalization of the various conjugates, chemical modification with fluorescein-isothiocyanate (FITC) was performed, and their stability over time was measured. Confocal microscopy was used to probe the uptake and confirm localization in the perinuclear region of the cancer cells. Flow cytometry assays confirmed that the bio-functionalization influence cellular uptake and the CCNs behavior depends on both cell line and surface features.
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http://dx.doi.org/10.3390/ma12091481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539763PMC
May 2019

H-NMR Metabolite Fingerprinting Analysis Reveals a Disease Biomarker and a Field Treatment Response in subsp. -Infected Olive Trees.

Plants (Basel) 2019 Apr 29;8(5). Epub 2019 Apr 29.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, I-73100 Lecce, Italy.

subsp. is a xylem-limited bacterial phytopathogen currently found associated on many hectares with the "olive quick decline syndrome" in the Apulia region (Southern Italy), and the cultivars Ogliarola salentina and Cellina di Nardò result in being particularly sensitive to the disease. In order to find compounds showing the capability of reducing the population cell density of the pathogen within the leaves, we tested, in some olive orchards naturally-infected by the bacterium, a zinc-copper-citric acid biocomplex, namely Dentamet®, by spraying it to the crown, once per month, during spring and summer. The occurrence of the pathogen in the four olive orchards chosen for the trial was molecularly assessed. A H NMR metabolomic approach, in conjunction with a multivariate statistical analysis, was applied to investigate the metabolic pattern of both infected and treated adult olive cultivars, Ogliarola salentina and Cellina di Nardò trees, in two sampling periods, performed during the first year of the trial. For both cultivars and sampling periods, the orthogonal partial least squares discriminant analysis (OPLS-DA) gave good models of separation according to the treatment application. In both cultivars, some metabolites such as quinic acid, the aldehydic form of oleoeuropein, ligstroside and phenolic compounds, were consistently found as discriminative for the untreated olive trees in comparison with the Dentamet®-treated trees. Quinic acid, a precursor of lignin, was confirmed as a disease biomarker for the olive trees infected by subsp. When treated with Dentamet®, the two cultivars showed a distinct response. A consistent increase in malic acid was observed for the Ogliarola salentina trees, whereas in the Cellina di Nardò trees the treatments attenuate the metabolic response to the infection. To note that in Cellina di Nardò trees at the first sampling, an increase in γ-aminobutyric acid (GABA) was observed. This study highlights how the infection incited by subsp. strongly modifies the overall metabolism of olive trees, and how a zinc-copper-citric acid biocomplex can induce an early re-programming of the metabolic pathways in the infected trees.
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http://dx.doi.org/10.3390/plants8050115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571561PMC
April 2019

[Pt('-acac)(γ-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells.

Biomolecules 2019 03 6;9(3). Epub 2019 Mar 6.

Laboratory of Cell Physiology, Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy.

We have demonstrated the cytotoxic effects of [Pt(,'-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(-acac)(γ-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo and in vitro. In the present paper, apoptotic and autophagic effects of [Pt(,'-acac)(γ-acac)(DMS)] and cisplatin were studied and compared using Caki-1 cancerous renal cells. The effects of cisplatin include activation of caspases, proteolysis of enzyme poly ADP ribose polymerase (PARP), control of apoptosis modulators B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and BH3-interacting domain death agonist (Bid), and cell cycle arrest in G2/M phase. Conversely, [Pt(,'-acac)(γ-acac)(DMS)] did not induce caspase activation, nor chromatin condensation or DNA fragmentation. The effects of [Pt(,-acac)(γ-acac)(DMS)] include microtubule-associated proteins 1A/1B light chain 3B (LC3)-I to LC3-II conversion, Beclin-1 and Atg-3, -4, and -5 increase, Bcl-2 decrease, and monodansylcadaverine accumulation in autophagic vacuoles. [Pt(,-acac)(γ-acac)(DMS)] also modulated various kinases involved in intracellular transduction regulating cell fate. [Pt(,'-acac)(γ-acac)(DMS)] inhibited the phosphorylation of mammalian target of rapmycin (mTOR), p70S6K, and AKT, and increased the phosphorylation of c-Jun N-terminal kinase (JNK1/2), a kinase activity pattern consistent with autophagy induction. In conclusion, while in past reports the high cytotoxicity of [Pt(,'-acac)(γ-acac)(DMS)] was always attributed to its ability to trigger an apoptotic process, in this paper we show that Caki-1 cells die as a result of the induction of a strong autophagic process.
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http://dx.doi.org/10.3390/biom9030092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468382PMC
March 2019

Variation in Membrane Trafficking Linked to SNARE AtSYP51 Interaction With Aquaporin NIP1;1.

Front Plant Sci 2018 9;9:1949. Epub 2019 Jan 9.

Laboratory of Botany, DISTEBA (Diartimento di Scienze e Tecnologie Biologiche e Ambientali), University of Salento, Lecce, Italy.

SYP51 and 52 are the two members of the SYP5 Qc-SNARE gene family in . These two proteins, besides their high level of sequence identity (85%), have shown to have differential functional specificity and possess a different interactome. Here we describe a unique and specific interaction of SYP51 with an ER aquaporin, AtNIP1;1 (also known as NLM1) indicated to be able to transport arsenite [As(III)] and previously localized on PM. In the present work we investigate in detail such localization and characterize the interaction with SYP51. We suggest that this interaction may reveal a new mechanism regulating tonoplast invagination and recycling. We propose this interaction to be part of a regulatory mechanism associated with direct membrane transport from ER to tonoplast and Golgi mediated vesicle trafficking. We also demonstrate that NIP1;1 is important for plant tolerance to arsenite but does not alter its uptake or translocation. To explain such phenomenon the hypothesis that SYP51/NIP1;1 interaction modifies ER and vacuole ability to accumulate arsenite is discussed.
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http://dx.doi.org/10.3389/fpls.2018.01949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334215PMC
January 2019

Modulation of RAB7A Protein Expression Determines Resistance to Cisplatin through Late Endocytic Pathway Impairment and Extracellular Vesicular Secretion.

Cancers (Basel) 2019 Jan 8;11(1). Epub 2019 Jan 8.

Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via Provinciale Lecce-Monteroni 165, 73100 Lecce, Italy.

Background: Cisplatin (CDDP) is widely used in treatment of cancer, yet patients often develop resistance with consequent therapeutical failure. In CDDP-resistant cells alterations of endocytosis and lysosomal functionality have been revealed, although their causes and contribution to therapy response are unclear.

Methods: We investigated the role of RAB7A, a key regulator of late endocytic trafficking, in CDDP-resistance by comparing resistant and sensitive cells using western blotting, confocal microscopy and real time PCR. Modulation of RAB7A expression was performed by transfection and RNA interference, while CDDP sensitivity and intracellular accumulation were evaluated by viability assays and chemical approaches, respectively. Also extracellular vesicles were purified and analyzed. Finally, correlations between RAB7A and chemotherapy response was investigated in human patient samples.

Results: We demonstrated that down-regulation of RAB7A characterizes the chemoresistant phenotype, and that RAB7A depletion increases CDDP-resistance while RAB7A overexpression decreases it. In addition, increased production of extracellular vesicles is modulated by RAB7A expression levels and correlates with reduction of CDDP intracellular accumulation.

Conclusions: We demonstrated, for the first time, that RAB7A regulates CDDP resistance determining alterations in late endocytic trafficking and drug efflux through extracellular vesicles.
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http://dx.doi.org/10.3390/cancers11010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357196PMC
January 2019

The Jellyfish (Cnidaria): Biochemical Composition of Ovaries and Antibacterial Lysozyme-like Activity of the Oocyte Lysate.

Mar Drugs 2018 Dec 29;17(1). Epub 2018 Dec 29.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov.le Lecce Monteroni, 73100 Lecce, Italy.

Jellyfish outbreaks in marine coastal areas represent an emergent problem worldwide, with negative consequences on human activities and ecosystem functioning. However, potential positive effects of jellyfish biomass proliferation may be envisaged as a natural source of bioactive compounds of pharmaceutical interest. We investigated the biochemical composition of mature female gonads and lysozyme antibacterial activity of oocytes in the Mediterranean barrel jellyfish . Chemical characterization was performed by means of multinuclear and multidimensional NMR spectroscopy. The ovaries of were mainly composed of water (93.7 ± 1.9% of wet weight), with organic matter (OM) and dry weight made respectively of proteins (761.76 ± 25.11 µg mg and 45.7 ± 1.5%), lipids (192.17 ± 10.56 µg mg and 9.6 ± 0.6%), and carbohydrates (59.66 ± 2.72 µg mg and 3.7 ± 0.3%). The aqueous extract of gonads contained free amino acids, organic acids, and derivatives; the lipid extract was composed of triglycerides (TG), polyunsaturated fatty acids (PUFAs), diunsaturated fatty acids (DUFAs), monounsaturated fatty acids (MUFAs), saturated fatty acids (SFAs), and minor components such as sterols and phospholipids. The oocyte lysate exhibited an antibacterial lysozyme-like activity (mean diameter of lysis of 9.33 ± 0.32 mm corresponding to 1.21 mg/mL of hen egg-white lysozyme). The occurrence of defense molecules is a crucial mechanism to grant healthy development of mature eggs and fertilized embryos (and the reproductive success of the species) by preventing marine bacterial overgrowth. As a corollary, these results call for future investigations for an exploitation of biomasses as a resource of bioactive metabolites of biotechnological importance including pharmaceuticals and nutrition.
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http://dx.doi.org/10.3390/md17010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356739PMC
December 2018

H-NMR-based metabolomic profiles of different sweet melon (Cucumis melo L.) Salento varieties: Analysis and comparison.

Food Res Int 2018 12 31;114:81-89. Epub 2018 Jul 31.

Di.S.Te.B.A., Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, prov.le Lecce Monteroni, Lecce, Italy. Electronic address:

Melon (Cucumis melo L.) is a significant source of substances able to provide human health benefits. From the 18th century in the Salento area (Apulia region), the cultivation of melon varieties (C. melo L.) has always been intense. Over the years, the production of this fruit has involved a large number of selected and preserved varieties in the different local districts. Unfortunately, most of the characteristics of locally grown vegetable varieties do not match the food industry requirements. Moreover, the agricultural land abandon leads these varieties to quickly disappear, thus affecting the intraspecific biodiversity. In order to characterize the inter-variety diversity of sweet melon (C. melo L. ssp. melo group inodorus) and the potential differences in the nutritional quality of fruits, a first investigation on the juice of five sweet melon varieties (locally known as "allungato", "scurzune", "egiziano", "minna de monaca", "pinto"), cultivated exclusively in the Salento area, was performed by H-NMR spectroscopy and Multivariate Analysis (MVA). The analysis grouped the samples into clusters according to the different variety. Interestingly, a different sugar (mono and disaccharides) content was observed among the grouped varieties, being sweetness the main characteristic of sweet melon quality and taste. A relative higher accumulation of monosaccharides (α-d and β-d glucose and α/β-d fructose) was found, in particular for the "minna de monaca" with respect to "allungato", "egiziano" and "pinto" varieties. Moreover, a marked high content of polyphenols and aromatic aminoacids as phenylalanine and tyrosine characterize the "allungato", "minna de monaca" and "pinto" varieties. An NMR-based metabolomic approach was used for the first time to describe these local landraces. This method may integrate other actions in order to achieving a reduction in the current rate of erosion of the biodiversity of Apulian horticultural species.
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http://dx.doi.org/10.1016/j.foodres.2018.07.045DOI Listing
December 2018

Traceability of "Tuscan PGI" Extra Virgin Olive Oils by ¹H NMR Metabolic Profiles Collection and Analysis.

Metabolites 2018 Sep 30;8(4). Epub 2018 Sep 30.

Department of Biological and Environmental Sciences and Technologies, University of Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy.

According to Coldiretti, Italy still continues to hold the European Quality record in extra virgin olive oils with origin designation and protected geographical indication (PDO and PGI). To date, 46 Italian brands are recognized by the European Union: 42 PDO and 4 PGI (Tuscan PGI, Calabria PGI; Tuscia PGI and PGI Sicily). Specific regulations, introduced for these quality marks, include the designation of both the geographical areas and the plant varieties contributing to the composition of the olive oil. However, the PDO and PGI assessment procedures are currently based essentially on farmer declarations. Tuscan PGI extra virgin olive oil is one of the best known Italian trademarks around the world. Tuscan PGI varietal platform is rather wide including 31 specific olive cultivars which should account for at least 95% of the product. On the other hand, while the characteristics of other popular Italian extra virgin olive oils (EVOOs) cultivars from specific geographical areas have been extensively studied (such as those of Coratina based blends from Apulia), little is still known about Tuscan PGI EVOO constituents. In this work, we performed, for the first time, a large-scale analysis of Tuscan PGI monocultivar olive oils by ¹H NMR spectroscopy and multivariate statistical analyses (MVA). After genetic characterization of 217 leaf samples from 24 selected geographical areas, distributed all over the Tuscany, a number of 202 micro-milled oil samples including 10 PGI cultivars, was studied. The results of the present work confirmed the need of monocultivar genetically certified EVOO samples for the construction of ¹H-NMR-metabolic profiles databases suitable for cultivar and/or geographical origin assessment. Such specific PGI EVOOs databases could be profitably used to justify the high added value of the product and the sustainability of the related supply chain.
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http://dx.doi.org/10.3390/metabo8040060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316653PMC
September 2018

Response of Cisplatin Resistant Skov-3 Cells to [Pt(-Acac)(γ-Acac)(DMS)] Treatment Revealed by a Metabolomic ¹H-NMR Study.

Molecules 2018 Sep 9;23(9). Epub 2018 Sep 9.

Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Monteroni, I-73100 Lecce, Italy.

The novel [Pt(,-acac)(γ-acac)(DMS)], Ptac2S, Pt(II) complex has recently gained increasing attention as a potential anticancer agent for its pharmacological activity shown in different tumor cell lines, studied both in vitro and in vivo. The mechanism of action of Ptac2S, operating on non-genomic targets, is known to be very different from that of -[PtCl₂(NH₃)₂], cisplatin, targeting nucleic acids. In this work, we evaluated the cytotoxicity of Ptac2S on the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells, by the MTT assay. A ¹H-NMR metabolomic approach coupled with multivariate statistical analysis was used for the first time for Ptac2S to figure out the biological mechanisms of action of the complex. The metabolic variations of intracellular metabolites and the composition of the corresponding extracellular culture media were compared to those of cisplatin (cells were treated at the IC doses of both drugs). The reported comparative metabolomic analysis revealed a very different metabolic profile between Ptac2S and cisplatin treated samples, thus confirming the different mechanism of action of Ptac2S also in the Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells line. In particular, higher levels of pyruvate were observed in Ptac2S treated, with respect to cisplatin treated, cells (in both aqueous and culture media). In addition, a very different lipid expression resulted after the exposure to the two drugs (Ptac2S and cisplatin). These results suggest a possible explanation for the Ptac2S ability to circumvent cisplatin resistance in SKOV-3 cells.
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http://dx.doi.org/10.3390/molecules23092301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225129PMC
September 2018

Beyond the mean: A comparison of trace- and macroelement correlation profiles of two lacustrine populations of the crayfish Procambarus clarkii.

Sci Total Environ 2018 May 27;624:1455-1466. Epub 2017 Dec 27.

CoNISMa, Consorzio Nazionale Interuniversitario per le Scienze del Mare, 00196 Roma, Italy; Department of Earth and Marine Sciences, University of Palermo, 90123 Palermo, Italy.

In invertebrate biomonitors of chemical pollution, emphasis has been generally given to mean accumulation patterns and how they reflect varying environmental levels of contamination. Intra-population variability, and how it relates with individual phenotypic traits, has received less attention. Here, a set of analytes including trace elements (B, Ba, Cd, Cr, Cu, Fe, Li, Mn, Ni, Pb, Sr, V, and Zn), macroelements (C, Ca, K, Mg, N, Na), and carbon and nitrogen stable isotopes (δC and δN) was measured in two populations of the crayfish Procambarus clarkii from Lake Trasimeno and Lake Bolsena (Central Italy). The influence of location, sex, body size, and condition factor was assessed; in addition, the analyte correlation profiles of the two populations were compared to verify their congruence. In general, significant inter-lake differences were observed in the concentration of both trace- and macroelements in crayfish tissues, generally mirroring the local chemistry of water and of benthic non-living matrices (sediment and plant detritus). Crayfish CN isotopic signatures excluded the occurrence of inter-lake variations in their omnivorous trophic habits. Correlation profiles varied considerably between the two populations in the nature and strength of bivariate relationships. However, Mantel tests and procrustean analyses indicated a general, significant congruence; C, N, and, to a lesser extent K, Li, Ni, Pb, and δC showed the highest procrustean residuals, suggesting that their associations with other analytes may be partially influenced by inter-population differences in growing phases. Our study indicates that the local geochemistry of the lacustrine environment influences the elemental fingerprint of Procambarus clarkii; the considerable inter-individual variability in the concentration of analytes, however, does not significantly reflect on their association, thus corroborating its effectiveness as an indicator species.
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http://dx.doi.org/10.1016/j.scitotenv.2017.12.106DOI Listing
May 2018

Cell-Penetrating CaCO₃ Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma.

Cancers (Basel) 2018 Jan 25;10(2). Epub 2018 Jan 25.

Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, Università del Salento & UdR INSTM di Lecce, Campus Universitario, Via Monteroni, 73100 Lecce, Italy.

Owing to their nano-sized porous structure, CaCO₃ nanocrystals (CaCO₃NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO₃NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO₃ NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration.
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http://dx.doi.org/10.3390/cancers10020031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836063PMC
January 2018

Metabolic profile comparison of fruit juice from certified sweet cherry trees (Prunus avium L.) of Ferrovia and Giorgia cultivars: A preliminary study.

Food Res Int 2016 Dec 12;90:281-287. Epub 2016 Nov 12.

University of Salento, DiSTeBA, Campus Ecotekne, via Prov.le Lecce-Monteroni, 73100 Lecce, Italy. Electronic address:

Sweet cherries are widely appreciated for fresh consumption as well as for production of juices, jams, jelly fruits and alcoholic beverages. The sweet cherry intake (as fresh fruit and related products) is extensively encouraged for their taste and nutritional qualities, due to the presence of water-soluble (C, B) and fat-soluble (A, E and K) vitamins, carotenoids, polyphenols and minerals, as well as glucose and fructose. However the market often endorses the consumption of a particular sweet cherry cultivar (as for most of vegetables) essentially for organoleptic and/or external appearance rather than nutraceutical qualities. In order to evaluate the potential difference in the nutritional quality of fruits, 56 sweet cherry juice samples from certified trees (Prunus avium L.) of two cultivars (30 from Ferrovia and 26 from Giorgia), grown in the same pedoclimatic Apulian region, were analyzed by H NMR spectroscopy and Multivariate Analysis (MVA). Interestingly, despite the usually lower commercial value with respect to the Ferrovia, Giorgia cultivar shows higher content of malic acid and phenolic compounds with important well known nutraceutical properties such as antioxidant activity and stimulating metabolism.
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http://dx.doi.org/10.1016/j.foodres.2016.11.014DOI Listing
December 2016