Publications by authors named "Tiziano Verri"

53 Publications

The Lepidopteran KAAT1 and CAATCH1: Orthologs to Understand Structure-Function Relationships in Mammalian SLC6 Transporters.

Neurochem Res 2021 Jul 24. Epub 2021 Jul 24.

Laboratory of Cellular and Molecular Physiology, Department of Biotechnology and Life Sciences, University of Insubria, via Dunant 3, 21100, Varese, Italy.

To the SLC6 family belong 20 human transporters that utilize the sodium electrochemical gradient to move biogenic amines, osmolytes, amino acids and related compounds into cells. They are classified into two functional groups, the Neurotransmitter transporters (NTT) and Nutrient amino acid transporters (NAT). Here we summarize how since their first cloning in 1998, the insect (Lepidopteran) Orthologs of the SLC6 family transporters have represented very important tools for investigating functional-structural relationships, mechanism of transport, ion and pH dependence and substate interaction of the mammalian (and human) counterparts.
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http://dx.doi.org/10.1007/s11064-021-03410-1DOI Listing
July 2021

Effects of Short-Term Fasting on mRNA Expression of Ghrelin and the Peptide Transporters PepT1 and 2 in Atlantic Salmon ().

Front Physiol 2021 21;12:666670. Epub 2021 Jun 21.

Department of Biological Sciences, University of Bergen, Bergen, Norway.

Food intake is a vital process that supplies necessary energy and essential nutrients to the body. Information regarding luminal composition in the gastrointestinal tract (GIT) collected through mechanical and nutrient sensing mechanisms are generally conveyed, in both mammals and fish, to the hypothalamic neurocircuits. In this context, ghrelin, the only known hormone with an orexigenic action, and the intestinal peptide transporters 1 and 2, involved in absorption of dietary di- and tripeptides, exert important and also integrated roles for the nutrient uptake. Together, both are potentially involved in signaling pathways that control food intake originating from different segments of the GIT. However, little is known about the role of different paralogs and their response to fasting. Therefore, after 3 weeks of acclimatization, 12 Atlantic salmon () post-smolt were fasted for 4 days to explore the gastrointestinal response in comparison with fed control ( = 12). The analysis covered morphometric (weight, length, condition factor, and wet content/weight fish %), molecular (gene expression variations), and correlation analyses. Such short-term fasting is a common and recommended practice used prior to any handling in commercial culture of the species. There were no statistical differences in length and weight but a significant lower condition factor in the fasted group. Transcriptional analysis along the gastrointestinal segments revealed a tendency of downregulation for both paralogous genes and and with significant lowered levels in the pyloric ceca for and in the pyloric ceca and midgut for . No differences were found for and (except a higher expression of the fasted group in the anterior midgut), supporting different roles for paralogs. This represents the first report on the effects of fasting on expressed in GIT in teleosts. Transcriptional analysis of ghrelin splicing variants ( and ) showed no difference between treatments. However, correlation analysis showed that the mRNA expression for all genes (restricted to segment with the highest levels) were affected by the residual luminal content. Overall, the results show minimal effects of 4 days of induced fasting in Atlantic salmon, suggesting that more time is needed to initiate a large GIT response.
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http://dx.doi.org/10.3389/fphys.2021.666670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255630PMC
June 2021

Human Leukocyte Antigen-DR Isotype Expression in Monocytes and T Cells Interferon-Gamma Release Assay in Septic Patients and Correlation With Clinical Outcome.

J Clin Med Res 2021 May 25;13(5):293-303. Epub 2021 May 25.

Clinical Pathology and Microbiology, Vito Fazzi General Hospital ASL-Lecce, Lecce, Italy.

Background: Sepsis is a life-threatening dysregulated host response to infection responsible of multiple organs dysfunction (Sepsis-3 International Consensus Definition), during which clinical outcome is a balance between inflammation and immune suppression. Monocytes and lymphocytes may play an important role in immune paralysis, and their impaired functional activity can decrease overall immune system efficiency. We evaluated sepsis-induced changes in monocytes human leukocyte antigen-DR isotype (HLA-DR) expression and T cell capacity of interferon (IFN)-γ production in relation with patient's clinical outcome.

Methods: Analysis of HLA-DR expression on blood monocytes (mHLA-DR) was performed in 55 patients with high procalcitonin (hPCT, > 0.5 ng/mL,) and suspected/confirmed sepsis, and 20 controls. HLA-DR absolute quantification and IFN-γ release assay were monitored in 16 septic patients for 4 weeks following sepsis confirmation.

Results: Cytofluorimetric analysis revealed a significant decrease of mHLA-DR percentage in septic patients with adverse outcome compared to patients with better clinical outcome (88.4% vs. 98.6% with P < 0.05), in combination with a significant decrease of absolute number of HLA-DR molecules per monocyte (P < 0.05, starting at 1 week of follow-up). Lymphocytes stimulation with phytohemagglutinin (PHA), () and () showed a severe declining of IFN-γ release related to fatal clinical outcome of patients.

Conclusions: This immunologic anergy of innate and adaptative immunity showed an early immune paralysis during sepsis which appears correlated with the impairment of clinical outcome.
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http://dx.doi.org/10.14740/jocmr4474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166289PMC
May 2021

Leptin receptor-deficient (knockout) zebrafish: Effects on nutrient acquisition.

Gen Comp Endocrinol 2021 Sep 4;310:113832. Epub 2021 Jun 4.

Department of Biological Sciences, University of Bergen, PO Box 7803, NO-5020 Bergen, Norway. Electronic address:

In mammals, knockout of LEPR results in a hyperphagic, morbid obese, and diabetic phenotype, which supports that leptin plays an important role in the control of appetite and energy metabolism, and that its receptor, LEPR, mediates these effects. To date, little is known about the role(s) of lepr in teleost physiology. We investigated a zebrafish (Danio rerio) homozygous lepr knockout (lepr) line generated by CRISPR/Cas9 in comparison to its wt counterpart with respect to nutrient acquisition, energy allocation, and metabolism. The metabolic characterization included oxygen consumption rate and morphometric parameters (yolk sac area, standard length, wet weight, and condition factor) as proxies for use and allocation of energy in developing (embryos, larvae, and juveniles) zebrafish and showed no particular differences between the two lines, in agreement with previous studies. One exception was found in oxygen consumption at 72 hpf, when zebrafish switch from embryonic to early larval stages and food-seeking behavior could be observed. In this case, the metabolic rate was significantly lower in lepr than in wt. Both phenotypes showed similar responses, with respect to metabolic rate, to acute alterations (22 and 34 °C) in water temperature (measured in terms of Q and activation energy) compared to the standard (28 °C) rearing conditions. To assess lepr involvement in signaling the processing and handling of incoming nutrients when an exogenous meal is digested and absorbed, we conducted an in vivo analysis in lepr and wt early (8 days post-fertilization) zebrafish larvae. The larvae were administered a bolus of protein hydrolysate (0%, 1%, 5%, and 15% lactalbumin) directly into the digestive tract lumen, and changes in the mRNA expression profile before and after (1 and 3 h) administration were quantified. The analysis showed transcriptional differences in the expressions of genes involved in the control of appetite and energy metabolism (cart, npy, agrp, and mc4r), sensing (casr, t1r1, t1r3, t1r2-1, t1r2-2, pept1a, and pept1b), and digestion (cck, pyy, try, ct, and amy), with more pronounced effects observed in the orexigenic than in the anorexigenic pathways, suggesting a role of lepr in their regulations. Differences in the mRNA levels of these genes in leprvs. wt larvae were also observed. Altogether, our analyses suggest an influence of lepr on physiological processes involved in nutrient acquisition, mainly control of food intake and digestion, during early development, whereas metabolism, energy allocation, and growth seem to be only slightly influenced.
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http://dx.doi.org/10.1016/j.ygcen.2021.113832DOI Listing
September 2021

Semi-interpenetrating polymer network cryogels based on poly(ethylene glycol) diacrylate and collagen as potential off-the-shelf platforms for cancer cell research.

J Biomed Mater Res B Appl Biomater 2021 Sep 11;109(9):1313-1326. Epub 2021 Jan 11.

Department of Engineering for Innovation, University of Salento, Lecce, Italy.

In the present work, we investigated the potential of novel semi-interpenetrating polymer network (semi-IPN) cryogels, obtained through ultraviolet exposure of aqueous mixtures of poly(ethylene glycol) diacrylate and type I collagen, as tunable off-the-shelf platforms for 3D cancer cell research. We synthesized semi-IPN cryogels with variable collagen amounts (0.1% and 1% w/v) and assessed the effect of collagen on key cryogel properties for cell culture, for example, porosity, degradation rate and mechanical stiffness. Then, we investigated the ability of the cryogels to sustain the long-term growth of two pancreatic ductal adenocarcinoma (PDAC) cell populations, the parenchymal Panc1 cells and their derived cancer stem cells. Results revealed that both cell lines efficiently infiltrated, attached and expanded in the cryogels over a period of 14 days. However, only when grown in the cryogels with the highest collagen concentration, both cell lines reproduced their characteristic growth pattern previously observed in collagen-enriched organotypic cultures, biomimetic of the highly fibrotic PDAC stroma. Cellular preembedding in Matrigel, that is, the classical approach to develop/grow organoids, interfered with an efficient intra-scaffold migration and growth. Although preliminary, these findings highlight the potential of the proposed cryogels as reproducible and tunable cancer cell research platforms.
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http://dx.doi.org/10.1002/jbm.b.34792DOI Listing
September 2021

Morpho-functional remodelling of the adult zebrafish (Danio rerio) heart in response to waterborne angiotensin II exposure.

Gen Comp Endocrinol 2021 Jan 19;301:113663. Epub 2020 Nov 19.

Department of Biology, Ecology and Earth Sciences, University of Calabria, Arcavacata di Rende, CS, Italy. Electronic address:

Angiotensin II (AngII), the principal effector of the Renin-Angiotensin System, is a pluripotent humoral agent whose biological actions include short-term modulations and long-term adaptations. In fish, short-term cardio-tropic effects of AngII are documented, but information on the role of AngII in long-term cardiac remodelling is not fully understood. Here, we describe a direct approach to disclose long-term morpho-functional effects of AngII on the zebrafish heart. Adult fish exposed to waterborne teleost analogue AngII for 8 weeks showed enhanced heart weight and cardio-somatic index, coupled to myocardial structural changes (i.e. augmented compacta thickness and fibrosis), and increased heart rate. These findings were paralleled by an up-regulation of type-1 and type-2 AngII receptors expression, and by changes in the expression of GATA binding protein 4, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 and superoxide dismutase 1 soluble mRNAs, as well as of cytochrome b-245 beta polypeptide protein, indicative of cardiac remodelling. Our results suggest that waterborne AngII can sustain and robustly affect the cardiac morpho-functional remodelling of adult zebrafish.
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http://dx.doi.org/10.1016/j.ygcen.2020.113663DOI Listing
January 2021

Allograft Inflammatory Factor-1 in Metazoans: Focus on Invertebrates.

Biology (Basel) 2020 Oct 24;9(11). Epub 2020 Oct 24.

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

Allograft inflammatory factor-1 (AIF-1) is a calcium-binding scaffold/adaptor protein often associated with inflammatory diseases. Originally cloned from active macrophages in humans and rats, this gene has also been identified in other vertebrates and in several invertebrate species. Among metazoans, AIF-1 protein sequences remain relatively highly conserved. Generally, the highest expression levels of are observed in immunocytes, suggesting that it plays a key role in immunity. In mammals, the expression of has been reported in different cell types such as activated macrophages, microglial cells, and dendritic cells. Its main immunomodulatory role during the inflammatory response has been highlighted. Among invertebrates, is involved in innate immunity, being in many cases upregulated in response to biotic and physical challenges. transcripts result ubiquitously expressed in all examined tissues from invertebrates, suggesting its participation in a variety of biological processes, but its role remains largely unknown. This review aims to present current knowledge on the role and modulation of and to highlight its function along the evolutionary scale.
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http://dx.doi.org/10.3390/biology9110355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692721PMC
October 2020

Evidence of Modular Responsiveness of Osteoblast-Like Cells Exposed to Hydroxyapatite-Containing Magnetic Nanostructures.

Biology (Basel) 2020 Oct 25;9(11). Epub 2020 Oct 25.

Laboratory of Applied Physiology, Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy.

The development of nanocomposites with tailored physical-chemical properties, such as nanoparticles containing magnetic iron oxides for manipulating cellular events at distance, implies exciting prospects in biomedical applications for bone tissue regeneration. In this context, this study aims to emphasize the occurrence of differential responsiveness in osteoblast-like cells to different nanocomposites with diverse features: dextran-grafted iron oxide (DM) nanoparticles and their hybrid nano-hydroxyapatite (DM/n-HA) counterpart. Here, responsiveness of cells in the presence of DMs or DM/n-HAs was evaluated in terms of cytoskeletal features. We observed that effects triggered by the DM are no more retained when DM is embedded onto the DM/n-HA nanocomposites. Also, analysis of mRNA level variations of the focal adhesion kinase (), and human genes showed that the DM/n-HA-treated cells retain tracts of physiological responsiveness compared to the DM-treated cells. Overall, a shielding effect by the n-HA component can be assumed, masking the DM's cytotoxic potential, also hinting a modular biomimicry of the nanocomposites respect to the physiological responses of osteoblast-like cells. In this view, the biocompatibility of n-HA together with the magnetic responsiveness of DMs represent an optimized combination of structural with functional features of the DM/n-HA nano-tools for bone tissue engineering, for finely acting within physiological ranges.
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http://dx.doi.org/10.3390/biology9110357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692879PMC
October 2020

Sequence analysis and spatiotemporal developmental distribution of the Cat-1-type transporter slc7a1a in zebrafish (Danio rerio).

Fish Physiol Biochem 2020 Dec 27;46(6):2281-2298. Epub 2020 Sep 27.

Department of Biological Sciences, University of Bergen, Postbox 7803, NO-5020, Bergen, Norway.

Cationic amino acid transporter 1 (Cat-1 alias Slc7a1) is a Na-independent carrier system involved in transport and absorption of the cationic amino acids lysine, arginine, histidine, and ornithine and has also been shown to be indispensable in a large variety of biological processes. Starting from isolated full-length zebrafish (Danio rerio) cDNA for slc7a1a, we performed comparative and phylogenetic sequence analysis, investigated the conservation of the gene during vertebrate evolution, and defined tissue expression during zebrafish development. Whole mount in situ hybridization first detected slc7a1a transcripts in somites, eyes, and brain at 14 h post-fertilization (hpf) with additional expression in the distal nephron at 24 hpf and in branchial arches at 3 days post-fertilization (dpf), with significant increase by 5 dpf. Taken together, the expression analysis of the zebrafish Cat-1 system gene slc7a1a suggests a functional role(s) during the early development of the central nervous system, muscle, gills, and kidney. Graphical abstract.
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http://dx.doi.org/10.1007/s10695-020-00873-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584565PMC
December 2020

Assessment of Cytocompatibility and Anti-Inflammatory (Inter)Actions of Genipin-Crosslinked Chitosan Powders.

Biology (Basel) 2020 Jul 8;9(7). Epub 2020 Jul 8.

Biomaterial Laboratory, Department of Innovation for Engineering, University of Salento c/o Ecotekne, 73100 Lecce, Italy.

Chitosan is a polysaccharide commonly used, together with its derivatives, in the preparation of hydrogel formulations, scaffolds and films for tissue engineering applications. Chitosan can be used as such, but it is commonly stabilized by means of chemical crosslinkers. Genipin is one of the crosslinkers that has been considered that is a crystalline powder extracted from the fruit of and processed to obtain an aglycon compound. Genipin is gaining interest in biological applications because of its natural origin and anti-inflammatory actions. In this paper, the ability of chitosan-based materials crosslinked with genipin to exert anti-inflammation properties in applications such as bone regeneration was studied. Powders obtained from chitosan-genipin scaffolds have been tested in order to mimic the natural degradation processes occurring during biomaterials implantation in vivo. The results from osteoblast-like cells showed that specific combinations of chitosan and genipin stimulate high permissiveness towards cells, with higher performance than the pure chitosan. In parallel, evidences from monocyte-like cells showed that the crosslinker, genipin, seems to promote slowing of the monocyte-macrophage transition at morphological level. This suggests a sort of modularity of pro-inflammatory versus anti-inflammatory behavior of our chitosan-based biomaterials. Being both the cell types exposed to microscale powders, as an added value our results bring information on the cell-material interactions in the degradative dynamics of chitosan scaffold structures during the physiological resorption processes.
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http://dx.doi.org/10.3390/biology9070159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407416PMC
July 2020

Effects of Olive Oil on Blood Pressure: Epidemiological, Clinical, and Mechanistic Evidence.

Nutrients 2020 May 26;12(6). Epub 2020 May 26.

Institute of Cardiology, University of Pisa, 56126 Pisa, Italy.

The increasing access to antihypertensive medications has improved longevity and quality of life in hypertensive patients. Nevertheless, hypertension still remains a major risk factor for stroke and myocardial infarction, suggesting the need to implement management of pre- and hypertensive patients. In addition to antihypertensive medications, lifestyle changes, including healthier dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet, have been shown to favorably affect blood pressure and are now recommended as integrative tools in hypertension management. An analysis of the effects of nutritional components of the Mediterranean diet(s) on blood pressure has therefore become mandatory. After a literature review of the impact of Mediterranean diet(s) on cardiovascular risk factors, we here analyze the effects of olive oil and its major components on blood pressure in healthy and cardiovascular disease individuals and examine underlying mechanisms of action. Both experimental and human studies agree in showing anti-hypertensive effects of olive oil. We conclude that due to its high oleic acid and antioxidant polyphenol content, the consumption of olive oil may be advised as the optimal fat choice in the management protocols for hypertension in both healthy and cardiovascular disease patients.
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http://dx.doi.org/10.3390/nu12061548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352724PMC
May 2020

Correction to: The peptide transporter 1a of the zebrafish , an emerging model in nutrigenomics and nutrition research: molecular characterization, functional properties, and expression analysis.

Genes Nutr 2020;15. Epub 2020 Feb 7.

2Department of Biological and Environmental Sciences and Technologies, University of Salento, via Provinciale Lecce-Monteroni, I-73100 Lecce, Italy.

[This corrects the article DOI: 10.1186/s12263-019-0657-3.].
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http://dx.doi.org/10.1186/s12263-020-0661-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006059PMC
February 2020

A Hidden Human Proteome Signature Characterizes the Epithelial Mesenchymal Transition Program.

Curr Pharm Des 2020 ;26(3):372-375

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

Background: Molecular changes associated with the initiation of the epithelial to mesenchymal transition (EMT) program involve alterations of large proteome-based networks. The role of protein products mapping to non-coding genomic regions is still unexplored.

Objective: The goal of this study was the identification of an alternative protein signature in breast cancer cellular models with a distinct expression of EMT markers.

Methods: We profiled MCF-7 and MDA-MB-231 cells using liquid-chromatography mass/spectrometry (LCMS/ MS) and interrogated the OpenProt database to identify novel predicted isoforms and novel predicted proteins from alternative open reading frames (AltProts).

Results: Our analysis revealed an AltProt and isoform protein signature capable of classifying the two breast cancer cell lines. Among the most highly expressed alternative proteins, we observed proteins potentially associated with inflammation, metabolism and EMT.

Conclusion: Here, we present an AltProts signature associated with EMT. Further studies will be needed to define their role in cancer progression.
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http://dx.doi.org/10.2174/1381612826666200129091610DOI Listing
November 2020

The peptide transporter 1a of the zebrafish , an emerging model in nutrigenomics and nutrition research: molecular characterization, functional properties, and expression analysis.

Genes Nutr 2019 19;14:33. Epub 2019 Dec 19.

2Department of Biological and Environmental Sciences and Technologies, University of Salento, via Provinciale Lecce-Monteroni, I-73100 Lecce, Italy.

Background: Peptide transporter 1 (PepT1, Slc15a1) mediates the uptake of dietary di/tripeptides in all vertebrates. However, in teleost fish, more than one PepT1-type transporter might function, due to specific whole genome duplication event(s) that occurred during their evolution leading to a more complex paralogue gene repertoire than in higher vertebrates (tetrapods).

Results: Here, we describe a novel di/tripeptide transporter in the zebrafish (), i.e., the zebrafish peptide transporter 1a (PepT1a; also known as Solute carrier family 15 member a1, Slc15a1a), which is a paralogue (78% similarity, 62% identity at the amino acid level) of the previously described zebrafish peptide transporter 1b (PepT1b, PepT1; also known as Solute carrier family 15 member 1b, Slc15a1b). Also, we report a basic analysis of the () mRNA expression levels in zebrafish adult tissues/organs and embryonic/early larval developmental stages. As assessed by expression in oocytes and two-electrode voltage clamp measurements, zebrafish PepT1a, as PepT1b, is electrogenic, Na-independent, and pH-dependent and functions as a low-affinity system, with values for Gly-Gln at - 60 mV of 6.92 mmol/L at pH 7.6 and 0.24 mmol/L at pH 6.5 and at - 120 mV of 3.61 mmol/L at pH 7.6 and 0.45 mmol/L at pH 6.5. Zebrafish mRNA is highly expressed in the intestine and ovary of the adult fish, while its expression in early development undergoes a complex trend over time, with mRNA being detected 1 and 2 days post-fertilization (dpf), possibly due to its occurrence in the RNA maternal pool, decreasing at 3 dpf (~ 0.5-fold) and increasing above the 1-2 dpf levels at 4 to 7 dpf, with a peak (~ 7-fold) at 6 dpf.

Conclusions: We show that the zebrafish PepT1a-type transporter is functional and co-expressed with () in the adult fish intestine. Its expression is also confirmed during the early phases of development when the yolk syncytial layer is present and yolk protein resorption processes are active. While completing the missing information on PepT1-type transporters function in the zebrafish, these results open to future investigations on the similar/differential role(s) of PepT1a/PepT1b in zebrafish and teleost fish physiology.
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http://dx.doi.org/10.1186/s12263-019-0657-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923934PMC
December 2019

Flow Cytometric Analysis of Monocytes Polarization and Reprogramming From Inflammatory to Immunosuppressive Phase During Sepsis.

EJIFCC 2019 Nov 25;30(4):371-384. Epub 2019 Nov 25.

Clinical Pathology and Microbiology Laboratory, Vito Fazzi General Hospital ASL-Lecce, Lecce, Italy.

Sepsis outcome is determined by a balance between inflammation and immune suppression. We aimed to evaluate monocytes polarization and reprogramming during these processes. We analyzed 93 patients with procalcitonin level >0.5 ng/mL (hPCT) and suspected/confirmed sepsis, and 84 controls by analysis of CD14, CD16 and HLA-DR expression on blood monocytes using fluorescent labeled monoclonal antibodies and BD FACS CANTO II. Complete blood cell count, procalcitonin and other biochemical markers were evaluated. Intermediate monocytes CD14CD16 increased in hPCT patients (including both positive and negative culture) compared to controls (13.6% ± 0.8 vs 6.2% ± 0.3, p<0.001), while classical monocytes CD14CD16were significantly reduced (72.5% ± 1.6 vs 82.6% ± 0.7, p<0.001). Among hPCT patients having positive microbial culture, the percentage of intermediate monocytes was significantly higher in septic compared with non-septic/localized-infection patients (17.4% vs 11.5%; p<0.05) whilst the percentage of classical monocytes was lower (68.0% vs 74.5%). Three-four days following the diagnosis of sepsis, HLA-DR expression on monocyte (mHLA-DR) was lower (94.3%) compared to controls (99.4%) (p<0.05). Septic patients with the worst clinical conditions showed higher incidence of secondary infections, longtime hospitalization and lower HLA-DR+ monocytes compared to septic patients with better clinical outcome (88.4% vs 98.6%, p=0.05). The dynamic nature of sepsis correlates with monocytes functional polarization and reprogramming from a pro-inflammatory CD14CD16 phenotype in non-septic hPCT patients to a decrease of HLA-DR surface expression in hPCT patients with confirmed sepsis, making HLA-DR reduction a marker of immune-paralysis and sepsis outcome. Analysis of monocytes plasticity opens to new mechanisms responsible for pro/anti-inflammatory responses during sepsis, and new immunotherapies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893894PMC
November 2019

Identification and characterization of the Atlantic salmon peptide transporter 1a.

Am J Physiol Cell Physiol 2020 01 30;318(1):C191-C204. Epub 2019 Oct 30.

Laboratory of General Physiology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy.

Peptide transporter 1 (PepT1) mediates the uptake of dietary di-/tripeptides in vertebrates. However, in teleost fish gut, more than one PepT1-type transporter might operate, because of teleost-specific whole gen(om)e duplication event(s) that occurred during evolution. Here, we describe a novel teleost di-/tripeptide transporter, i.e., the Atlantic salmon () peptide transporter 1a [PepT1a; or solute carrier family 15 member 1a (Slc15a1a)], which is a paralog (77% similarity and 64% identity at the amino acid level) of the well-described Atlantic salmon peptide transporter 1b [PepT1b, alias PepT1; or solute carrier family 15 member 1b (Slc15a1b)]. Comparative analysis and evolutionary relationships of gene/protein sequences were conducted after ad hoc database mining. Tissue mRNA expression analysis was performed by quantitative real-time PCR, whereas transport function analysis was accomplished by heterologous expression in oocytes and two-electrode voltage-clamp measurements. Atlantic salmon is highly expressed in the proximal intestine (pyloric ceca ≈ anterior midgut > midgut >> posterior midgut), in the same gut regions as but notably ~5-fold less abundant. Like PepT1b, Atlantic salmon PepT1a is a low-affinity/high-capacity system. Functional analysis showed electrogenic, Na-independent/pH-dependent transport and apparent substrate affinity () values for Gly-Gln of 1.593 mmol/L at pH 7.6 and 0.076 mmol/L at pH 6.5. In summary, we show that a piscine PepT1a-type transporter is functional. Defining the role of Atlantic salmon PepT1a in the gut will help to understand the evolutionary and functional relationships among peptide transporters. Its functional characterization will contribute to elucidate the relevance of peptide transporters in Atlantic salmon nutritional physiology.
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http://dx.doi.org/10.1152/ajpcell.00360.2019DOI Listing
January 2020

Hydroxytyrosol Modulates Adipocyte Gene and miRNA Expression Under Inflammatory Condition.

Nutrients 2019 Oct 17;11(10). Epub 2019 Oct 17.

Cardiology Division, Pisa University Hospital, 56126 Pisa, Italy.

Chronic inflammation of the adipose tissue (AT) is a major contributor to obesity-associated cardiometabolic complications. The olive oil polyphenol hydroxytyrosol (HT) contributes to Mediterranean diet cardiometabolic benefits through mechanisms still partially unknown. We investigated HT (1 and 10 μmol/L) effects on gene expression (mRNA and microRNA) related to inflammation induced by 10 ng/mL tumor necrosis factor (TNF)-α in human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. At real-time PCR, HT significantly inhibited TNF-α-induced mRNA levels, of monocyte chemoattractant protein-1, C-X-C Motif Ligand-10, interleukin (IL)-1β, IL-6, vascular endothelial growth factor, plasminogen activator inhibitor-1, cyclooxygenase-2, macrophage colony-stimulating factor, matrix metalloproteinase-2, Cu/Zn superoxide dismutase-1, and glutathione peroxidase, as well as surface expression of intercellular adhesion molecule-1, and reverted the TNF-α-mediated inhibition of endothelial nitric oxide synthase, peroxisome proliferator-activated receptor coactivator-1α, and glucose transporter-4. We found similar effects in adipocytes stimulated by macrophage-conditioned media. Accordingly, HT significantly counteracted miR-155-5p, miR-34a-5p, and let-7c-5p expression in both cells and exosomes, and prevented NF-κB activation and production of reactive oxygen species. HT can therefore modulate adipocyte gene expression profile through mechanisms involving a reduction of oxidative stress and NF-κB inhibition. By such mechanisms, HT may blunt macrophage recruitment and improve AT inflammation, preventing the deregulation of pathways involved in obesity-related diseases.
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http://dx.doi.org/10.3390/nu11102493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836288PMC
October 2019

Fishing in the Cell Powerhouse: Zebrafish as A Tool for Exploration of Mitochondrial Defects Affecting the Nervous System.

Int J Mol Sci 2019 May 15;20(10). Epub 2019 May 15.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Piazza Giulio Cesare 11, 70124 Bari, Italy.

The zebrafish () is a small vertebrate ideally suited to the modeling of human diseases. Large numbers of genetic alterations have now been modeled and could be used to study organ development by means of a genetic approach. To date, limited attention has been paid to the possible use of the zebrafish toolbox in studying human mitochondrial disorders affecting the nervous system. Here, we review the pertinent scientific literature discussing the use of zebrafish in modeling gene mutations involved in mitochondria-related neurological human diseases. A critical analysis of the literature suggests that the zebrafish not only lends itself to exploration of the pathological consequences of mitochondrial energy output on the nervous system but could also serve as an attractive platform for future drugs in an as yet untreatable category of human disorders.
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http://dx.doi.org/10.3390/ijms20102409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567007PMC
May 2019

Bioactive chitosan-based scaffolds with improved properties induced by dextran-grafted nano-maghemite and l-arginine amino acid.

J Biomed Mater Res A 2019 06 12;107(6):1244-1252. Epub 2019 Feb 12.

Department of Engineering for Innovation, University of Salento, Lecce, Italy.

Over the past years, fundamentals of magnetism opened a wide research area of interest, in the field of tissue engineering and regenerative medicine. The integration of magnetic nanoarchitectures into synthetic/natural scaffold formulations allowed obtaining "on demand" responsive structures able to guide the regeneration process. The aim of this work was the design and characterization of three-dimensional (3D) chitosan-based scaffolds containing dextran-grafted maghemite nanoarchitectures (DM) and functionalized with l-arginine (l-Arg) amino acid as bioactive agent. A homogeneous pore distribution and a high degree of interconnection were obtained for all the structures with DMs, which resulted well distributed inside the polymer matrix. All the results suggest that the simultaneous presence of DMs and l-Arg conferred interesting mechano-structural and bioactive properties toward osteoblast-like and human mesenchymal stem cells, differentially stimulating their proliferation both in the absence and in the presence of a time-dependent magnetic field. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1244-1252, 2019.
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http://dx.doi.org/10.1002/jbm.a.36633DOI Listing
June 2019

Type II Na-phosphate Cotransporters and Phosphate Balance in Teleost Fish.

Pflugers Arch 2019 01 12;471(1):193-212. Epub 2018 Dec 12.

Epithelial Research Group, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.

Teleost fish are excellent models to study the phylogeny of the slc34 gene family, Slc34-mediated phosphate (P) transport and how Slc34 transporters contribute P homeostasis. Fish need to accumulate P from the diet to sustain growth. Much alike in mammals, intestinal uptake in fish is partly a paracellular and partly a Slc34-mediated transcellular process. Acute regulation of P balance is achieved in the kidney via a combination of Slc34-mediated secretion and/or reabsorption. A great plasticity is observed in how various species perform and combine the different processes of secretion and reabsorption. A reason for this diversity is found in one or two whole genome duplication events followed by potential gene loss; consequently, teleosts exhibit distinctly different repertoires of Slc34 transporters. Moreover, due to habitats with vastly different salinity, teleosts face the challenge of either preserving water in a hyperosmotic environment (seawater) or excreting water in hypoosmotic freshwater. An additional challenge in understanding teleost P homeostasis are the genome duplication and retention events that diversified peptide hormones such as parathyroid hormone and stanniocalcin. Dietary P and non-coding RNAs also regulate the expression of piscine Slc34 transporters. The adaptive responses of teleost Slc34 transporters to e.g. P diets and vitamin D are informative in the context of comparative physiology, but also relevant in applied physiology and aquaculture. In fact, P is essential for teleost fish growth but it also exerts significant adverse consequences if over-supplied. Thus, investigating Slc34 transporters helps tuning the physiology of commercially valuable teleost fish in a confined environment.
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http://dx.doi.org/10.1007/s00424-018-2239-4DOI Listing
January 2019

Carnosine modulates the Sp1-Slc31a1/Ctr1 copper-sensing system and influences copper homeostasis in murine CNS-derived cells.

Am J Physiol Cell Physiol 2019 02 28;316(2):C235-C245. Epub 2018 Nov 28.

Laboratory of General Physiology, Department of Biological and Environmental Sciences and Technologies, University of Salento , Lecce , Italy.

Carnosine (CAR) is an endogenous dipeptide physiologically present in excitable tissues, such as central nervous system (CNS) and muscle. CAR is acknowledged as a substrate involved in many homeostatic pathways and mechanisms and, due to its biochemical properties, as a molecule intertwined with the homeostasis of heavy metals such as copper (Cu). In CNS, Cu excess and dysregulation imply oxidative stress, free-radical production, and functional impairment leading to neurodegeneration. Here, we report that CAR intercepts the regulatory routes of Cu homeostasis in nervous cells and tissues. Specifically, in a murine neuron-derived cell model, i.e., the B104 neuroblastoma cells, extracellular CAR exposure up to 24 h influenced intracellular Cu entry and affected (downregulated) the key Cu-sensing system, consisting of the gene coding for the Slc31a1 transmembrane Cu importer (alias Ctr1), and the gene coding for the Cu-responsive transcription factor Sp1 ( Sp1). Also, CAR exposure upregulated CAR biosynthesis ( Carns1), extracellular degradation ( Cndp1), and transport ( Slc15a4, alias Pht1) genes and elicited CAR intracellular accumulation, contributing to the outline of functional association between CAR and Cu within the cell. Interestingly, the same gene modulation scheme acting in vitro operates in vivo in brains of mice undergoing dietary administration of CAR in drinking water for 2 wk. Overall, our findings describe for the first time a regulatory interaction between CAR and Cu pathways in CNS and indicate CAR as a novel active molecule within the network of ligands and chaperones that physiologically regulate Cu homeostasis.
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http://dx.doi.org/10.1152/ajpcell.00106.2018DOI Listing
February 2019

Dissecting KMT2D missense mutations in Kabuki syndrome patients.

Hum Mol Genet 2018 11;27(21):3651-3668

Division of Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.

Kabuki syndrome is a rare autosomal dominant condition characterized by facial features, various organs malformations, postnatal growth deficiency and intellectual disability. The discovery of frequent germline mutations in the histone methyltransferase KMT2D and the demethylase KDM6A revealed a causative role for histone modifiers in this disease. However, the role of missense mutations has remained unexplored. Here, we expanded the mutation spectrum of KMT2D and KDM6A in KS by identifying 37 new KMT2D sequence variants. Moreover, we functionally dissected 14 KMT2D missense variants, by investigating their impact on the protein enzymatic activity and the binding to members of the WRAD complex. We demonstrate impaired H3K4 methyltransferase activity in 9 of the 14 mutant alleles and show that this reduced activity is due in part to disruption of protein complex formation. These findings have relevant implications for diagnostic and counseling purposes in this disease.
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http://dx.doi.org/10.1093/hmg/ddy241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488975PMC
November 2018

Responsiveness of Carnosine Homeostasis Genes in the Pancreas and Brain of Streptozotocin-Treated Mice Exposed to Dietary Carnosine.

Int J Mol Sci 2018 06 9;19(6). Epub 2018 Jun 9.

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

In excitable tissues, the endogenous dipeptide carnosine (CAR, β-Ala-l-His) sustains homeostatic responses to various challenges. By eliciting hypoglycemic effects via actions on the autonomic nervous system and protection of pancreatic beta-cells, CAR is also relevant in diabetes. We investigated the expression of genes involved in CAR biosynthesis, degradation, and membrane transport pathways, in the pancreas and brains of mice treated with streptozotocin (STZ) and then exposed to dietary CAR. We induced hyperglycemia by STZ intraperitoneal injections; then, STZ-treated mice received drinking water with or without CAR for two weeks. We report that CAR administration elicits beneficial effects on blood glucose levels and weight loss in STZ-treated mice and, remarkably, on the insulin gene products in the pancreas, preserving gene expression from STZ challenge. Also, we describe mRNA downregulation of the / (dipeptide transporter) and (intracellular dipeptidase) genes in the pancreas of hyperglycemic mice, and dysregulation of (CAR synthase), and in brains; interestingly, dietary CAR elicits counteracting effects. These expression patterns associate with variations of CAR content in tissues of mice. Overall, our report suggests a direct role of CAR in the diabetes-affected pancreas and in the diabetes-targeted CNS, proposing (dys)regulation of CAR’s homeostasis as a marker condition.
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http://dx.doi.org/10.3390/ijms19061713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032234PMC
June 2018

Molecular and expression analysis of the Allograft inflammatory factor 1 (AIF-1) in the coelomocytes of the common sea urchin Paracentrotus lividus.

Fish Shellfish Immunol 2017 Dec 3;71:136-143. Epub 2017 Oct 3.

Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, Università Del Salento, Complesso Ecotekne Pal. A, Via Prov.le Lecce Monteroni, 73100 Lecce, Italy. Electronic address:

Allograft inflammatory factor 1 (AIF-1) is a highly conserved gene involved in inflammation, cloned and characterized in several evolutionary distant animal species. Here, we report the molecular identification, characterization and expression of AIF-1 from the common sea urchin Paracentrotus lividus. In this species, AIF-1 encodes a predicted 151 amino acid protein with high similarity to vertebrate AIF-1 proteins. Immunocytochemical analyses on coelomocytes reveal localization of the AIF-1 protein in amoebocytes (perinuclear cytoplasmic zone) and red sphaerulocytes (inside granules), but not in vibratile cells and colorless sphaerula cells. The significant increase of AIF-1 expression (mRNA and protein) found in the coelomocytes of the sea urchin after Gram + bacterial challenge suggests the involvement of AIF-1 in the inflammatory response. Our analysis on P. lividus AIF-1 contributes to elucidate AIF-1 function along the evolutionary scale and consolidate the key evolutionary position of echinoderms throughout metazoans with respect to the common immune paths.
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http://dx.doi.org/10.1016/j.fsi.2017.09.078DOI Listing
December 2017

Human bocavirus: Current knowledge and future challenges.

World J Gastroenterol 2016 Oct;22(39):8684-8697

Marcello Guido, Francesca Serio, Mattia De Giorgi, Antonella De Donno, Francesco Bagordo, Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, Faculty of Sciences, University of Salento, 73100 Lecce, Italy.

Human bocavirus (HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate (HBoV1), namely HBoV2, HBoV3 and HBoV4, have been detected principally in human faeces. HBoVs are small non-enveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1 (NS1) and nuclear phosphoprotein (NP1) and the third the viral capsid proteins 1 and 2 (VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in cell cultures, and the fact that HBoV infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzyme-linked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoVs as true pathogen or innocent bystander is also emphasized.
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http://dx.doi.org/10.3748/wjg.v22.i39.8684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075545PMC
October 2016

N7-platinated ribonucleotides are not incorporated by RNA polymerases. New perspectives for a rational design of platinum antitumor drugs.

J Inorg Biochem 2016 10 8;163:143-146. Epub 2016 Jul 8.

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

In this work, we assessed the capacity of RNA polymerases to use platinated ribonucleotides as substrates for RNA synthesis by testing the incorporation of the model compound [Pt(dien)(N7-5'-GTP)] (dien=diethylenetriamine; GTP=5'-guanosine triphosphate) into a natural RNA sequence. The yield of in vitro transcription operated by T7 RNA polymerase, on the LacZ (Escherichia coli gene encoding for β-galactosidase) sequence, decreases progressively with decreasing the concentration of natural GTP, in favor of the platinated nucleotide, [Pt(dien)(N7-5'-GTP)]. Comparison of the T7 RNA polymerase transcription activities for [Pt(dien)(N7-5'-GTP)] compound incorporation reaction test, with respect to the effect of a decreasing concentration of natural GTP, showed no major differences. A specific inhibitory effect of compound [Pt(dien)(N7-5'-GTP)] (which may pair the complementary base on the DNA strand, without being incorporated in the RNA by the T7 RNA polymerase) was evidenced. Our findings therefore suggest that RNA polymerases, unlike DNA polymerases, are unable to incorporate N7-platinated nucleotides into newly synthesized nucleic acids. In this respect, specifically designed N7-platinated nucleotides based compounds could be used in alternative to the classical platinum based drugs. This approach may offer a possible strategy to target specifically DNA, without affecting RNA, and is potentially able to better modulate pharmacological activity.
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http://dx.doi.org/10.1016/j.jinorgbio.2016.07.004DOI Listing
October 2016

Di- and tripeptide transport in vertebrates: the contribution of teleost fish models.

J Comp Physiol B 2017 Apr 1;187(3):395-462. Epub 2016 Nov 1.

Neuropathology Unit, Institute of Experimental Neurology and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Solute Carrier 15 (SLC15) family, alias H-coupled oligopeptide cotransporter family, is a group of membrane transporters known for their role in the cellular uptake of di- and tripeptides (di/tripeptides) and peptide-like molecules. Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from dietary protein digestion, while SLC15A2 (PEPT2) mainly allows renal tubular reabsorption of di/tripeptides from ultrafiltration, SLC15A3 (PHT2) and SLC15A4 (PHT1) possibly interact with di/tripeptides and histidine in certain immune cells, and SLC15A5 has unknown function. Our understanding of this family in vertebrates has steadily increased, also due to the surge of genomic-to-functional information from 'non-conventional' animal models, livestock, poultry, and aquaculture fish species. Here, we review the literature on the SLC15 transporters in teleost fish with emphasis on SLC15A1 (PEPT1), one of the solute carriers better studied amongst teleost fish because of its relevance in animal nutrition. We report on the operativity of the transporter, the molecular diversity, and multiplicity of structural-functional solutions of the teleost fish orthologs with respect to higher vertebrates, its relevance at the intersection of the alimentary and osmoregulative functions of the gut, its response under various physiological states and dietary solicitations, and its possible involvement in examples of total body plasticity, such as growth and compensatory growth. By a comparative approach, we also review the few studies in teleost fish on SLC15A2 (PEPT2), SLC15A4 (PHT1), and SLC15A3 (PHT2). By representing the contribution of teleost fish to the knowledge of the physiology of di/tripeptide transport and transporters, we aim to fill the gap between higher and lower vertebrates.
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http://dx.doi.org/10.1007/s00360-016-1044-7DOI Listing
April 2017

Efficacy of silver coated surgical sutures on bacterial contamination, cellular response and wound healing.

Mater Sci Eng C Mater Biol Appl 2016 Dec 29;69:884-93. Epub 2016 Jul 29.

Department of Engineering for Innovation, University of Salento, Via Monteroni, 73100 Lecce, Italy.

The resistance demonstrated by many microorganisms towards conventional antibiotics has stimulated the interest in alternative antimicrobial agents and in novel approaches for prevention of infections. Silver, a natural braod-spectrum antimicrobial agent known since antiquity, has been widely employed in biomedical field due to its recognized antibacterial, antifungal and antiviral properties. In this work, antibacterial silver coatings were deposited on absorbable surgical sutures through the in situ photo-chemical deposition of silver clusters. Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDX) and thermo-gravimetric analysis (TGA) were performed in order to investigate the presence and distribution of the silver clusters on the substrate. The amounts of silver deposited and released by the silver treated sutures were calculated through Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS), and the results were related to the biodegradation of the material. The microbiological properties and the potential cytotoxicity of the silver-treated sutures were investigated in relation with hydrolysis experiments, in order to determine the effect of the degradation on antibacterial properties and biocompatibility.
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http://dx.doi.org/10.1016/j.msec.2016.07.074DOI Listing
December 2016

Dolichol-phosphate mannose synthase depletion in zebrafish leads to dystrophic muscle with hypoglycosylated α-dystroglycan.

Biochem Biophys Res Commun 2016 08 10;477(1):137-143. Epub 2016 Jun 10.

Molecular Medicine, IRCCS Stella Maris, Via dei Giacinti 2, 56128, Pisa, Italy. Electronic address:

Defective dolichol-phosphate mannose synthase (DPMS) complex is a rare cause of congenital muscular dystrophy associated with hypoglycosylation of alpha-dystroglycan (α-DG) in skeletal muscle. We used the zebrafish (Danio rerio) to model muscle abnormalities due to defects in the subunits of DPMS. The three zebrafish ortholog subunits (encoded by the dpm1, dpm2 and dpm3 genes, respectively) showed high similarity to the human proteins, and their expression displayed localization in the midbrain/hindbrain area and somites. Antisense morpholino oligonucleotides targeting each subunit were used to transiently deplete the dpm genes. The resulting morphant embryos showed early death, muscle disorganization, low DPMS complex activity, and increased levels of apoptotic nuclei, together with hypoglycosylated α-DG in muscle fibers, thus recapitulating most of the characteristics seen in patients with mutations in DPMS. Our results in zebrafish suggest that DPMS plays a role in stabilizing muscle structures and in apoptotic cell death.
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http://dx.doi.org/10.1016/j.bbrc.2016.06.033DOI Listing
August 2016

Adsorption of the cis-[Pt(NH3)2(P2O7)](2-) (phosphaplatin) on hydroxyapatite nanocrystals as a smart way to selectively release activated cis-[Pt(NH3)2Cl2] (cisplatin) in tumor tissues.

J Inorg Biochem 2016 Apr 20;157:73-9. Epub 2016 Jan 20.

University of Salento, Department of Biological and Environmental Sciences and Technologies, Via Monteroni, 73100 Lecce, Italy. Electronic address:

The relevant adsorption of cis-[Pt(NH3)2(P2O7)](2-) (phosphaplatin) on hydroxyapatite nanocrystals (nHAP) was observed and studied in water suspension. Phosphaplatin cytotoxicity, which is very low for HeLa, MCF-7 and HS-5 cell lines could be enhanced, reaching that of cisplatin, by interaction with solid nHAP. This effect stems from nHAP ability to catalyze the phosphaplatin hydrolysis, producing the same hydrolytic species responsible for cisplatin antitumor activity.
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http://dx.doi.org/10.1016/j.jinorgbio.2016.01.019DOI Listing
April 2016
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