@article{%a1.%Yb_116,

title = {Discovery of first novel sigma/HDACi dual-ligands with a potent in vitro antiproliferative activity},

author = {Barbaraci C and di Giacomo V and Maruca A and Patamia V and Rocca R and Dichiara M and {Di Rienzo} A and Cacciatore I and Cataldi A and Balaha M and Rapino M and Zagni C and Zampieri D and Pasquinucci L and Parenti C and Amata E and Rescifina A and Alcaro S and Marrazzo A.},

url = {https://www.sciencedirect.com/science/article/pii/S0045206823004558?via%3Dihub},

doi = {10.1016/j.bioorg.2023.106794},

year  = {2023},

date = {2023-10-02},

journal = {Bioorganic chemistry},

volume = {140},

pages = {106794},

abstract = {Designing and discovering compounds for dual-target inhibitors is challenging to synthesize new, safer, and more efficient drugs than single-target drugs, especially to treat multifactorial diseases such as cancer. The simultaneous regulation of multiple targets might represent an alternative synthetic approach to optimize patient compliance and tolerance, minimizing the risk of target-based drug resistance due to the modulation of a few targets. To this end, we conceived for the first time the design and synthesis of dual-ligands σR/HDACi to evaluate possible employment as innovative candidates to address this complex disease. Among all synthesized compounds screened for several tumoral cell lines, compound 6 (Kiσ1R = 38 ± 3.7; Kiσ2R = 2917 ± 769 and HDACs IC50 = 0.59 µM) is the most promising candidate as an antiproliferative agent with an IC50 of 0.9 µM on the HCT116 cell line and no significant toxicity to normal cells. Studies of molecular docking, which confirmed the affinity over σ1R and a pan-HDACs inhibitory behavior, support a possible balanced affinity and activity between both targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb,

title = {Dynamic susceptibility MR perfusion imaging of the brain: not a question of contrast agent molarity},

author = {Panara V and Chiacchiaretta P and Rapino M and Maruotti V and Parenti M and Piccirilli E and Pizzi AD and Caulo M},

url = {https://link.springer.com/article/10.1007%2Fs00234-021-02807-7},

doi = {10.1007/s00234-021-02807-7},

year  = {2022},

date = {2022-04-13},

urldate = {2022-04-13},

journal = {Neuroradiology},

volume = {64},

issue = {4},

pages = {685-692},

abstract = {Purpose: Dynamic susceptibility contrast (DSC) perfusion-weighted MR imaging (PWI) is increasingly used in clinical neuroimaging for a range of conditions. More highly concentrated GBCAs (e.g., gadobutrol) are often preferred for DSC imaging because it is thought that more Gd is present in the volume of interest during first pass for a given equivalent injection rate. However, faster injection of a less viscous GBCA (e.g., gadoteridol) might generate a more compact and narrower contrast bolus thus obviating any perceived benefit of higher Gd concentration. This preliminary study aimed to analyze and compare DSC examinations in the healthy brain hemisphere of patients with brain tumors using gadobutrol and gadoteridol administered at injection rates of 4 and 6 mL/s. Methods: Thirty-nine brain tumor patients studied with DSC-PWI were evaluated. A simplified gamma-variate model function was applied to calculate the mean peak, area under the curve (AUC), and full-width at half-maximum (FHWM) of concentration-time curves derived from ΔR2* signals at four different regions-of-interest (ROIs). Qualitative assessment of the derived CBV maps was also performed independently by 2 neuroradiologists. Results: No qualitative or quantitative differences between the two GBCAs were observed when administered at a flow rate of 4 mL/s. At a flow rate of 6 mL/s, gadoteridol showed lower FWHM values. Conclusion: Gadobutrol and gadoteridol are equivalent for clinical assessment of qualitative CBV maps and quantitative perfusion parameters (FHWM) at a flow rate of 4 mL/s. At 6 mL/s, gadoteridol produces a narrower bolus shape and potentially improves quantitative assessment of perfusion parameters.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Ybm,

title = {Novel Perceptions on Chemical Profile and Biopharmaceutical Properties of Mentha spicata Extracts: Adding Missing Pieces to the Scientific Puzzle},

author = {Zengin G and Ak G and Ceylan R and Uysal S and Llorent-Martínez E and Di Simone SC and Rapino M and Acquaviva A and Libero ML and Chiavaroli A and Recinella L and Leone S and Brunetti L and Cataldi A and Orlando G and Menghini L and Ferrante C and Balaha M and di Giacomo V},

url = {https://www.mdpi.com/2223-7747/11/2/233},

doi = {10.3390/plants11020233},

year  = {2022},

date = {2022-03-21},

journal = {Plants (Basel)},

volume = {11},

issue = {2},

pages = {233},

abstract = {Mentha spicata is one of the most popular species in the genus, and it is of great interest as a gastrointestinal and sedative agent in the folk medicine system. In this study, different M. spicata extracts, obtained by the use of four solvents (hexane, chloroform, acetone and acetone/water) were chemically characterized using HPLC-ESI-MS n, which allowed for identification of 27 phenolic compounds. The extracts' antioxidant and enzyme inhibitory properties were investigated. In addition, neuroprotective effects were evaluated in hypothalamic HypoE22 cells, and the ability of the extracts to prevent the hydrogen peroxide-induced degradation of dopamine and serotonin was observed. The best antioxidant effect was achieved for all the extraction methods using acetone/water as a solvent. These extracts were the richest in acacetin, eriodictyol, hesperidin, sagerinic acid, naringenin, luteolin, chlorogenic acid, chrysoeriol and apigenin. The intrinsic antioxidant and enzyme inhibition properties of the acetone/water extract could also explain, albeit partially, its efficacy in preventing prostaglandin E2 overproduction and dopamine depletion (82.9% turnover reduction) in HypoE22 cells exposed to hydrogen peroxide. Thus, our observations can provide a scientific confirmation of the neuromodulatory and neuroprotective effects of M. spicata.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__498,

title = {Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens},

author = {di Giacomo V and Recinella L and Chiavaroli A and Orlando G and Cataldi A and Rapino M and Di Valerio V and Politi M and Antolini MD and Acquaviva A and Bacchin F and Di Mascio M and Leone S and Brunetti L and Menghini L and Carradori S and Zengin G and Ak G and Ferrante C},

url = {https://www.mdpi.com/2076-3921/10/1/44},

doi = {10.3390/antiox10010044},

year  = {2021},

date = {2021-03-09},

journal = {Antioxidants (Basel)},

volume = {10},

number = {1},

pages = {44},

abstract = {Industrial hemp is a multiuse crop whose phytocomplex includes terpenophenolics and flavonoids. In the present study, the phenolic and terpenophenolic compounds were assayed in the water extract of the hemp variety Futura 75. Protective effects were also investigated in human fibroblast and keratinocytes and isolate mouse skin specimens, which were exposed to hydrogen peroxide and/or to the extract (1-500 µg/mL). The results of phytochemical analysis suggested the cannabidiol, cannabidiolic acid and rutin as the prominent phytocompounds. In the in vitro system represented by human keratinocytes and fibroblasts, the hemp extract was found to be able to protect cells from cytotoxicity and apoptosis induced by oxidative stress. Moreover, modulatory effects on IL-6, a key mediator in skin proliferation, were found. In isolated rat skin, the extract reduced hydrogen peroxide-induced l-dopa turnover, prostaglandin-E2 production and the ratio kynurenine/tryptpophan, thus corroborating anti-inflammatory/antioxidant effects. The in silico docking studies also highlighted the putative interactions between cannabidiol, cannabidiolic acid and rutin with tyrosinase and indoleamine-2,3-dioxygenase, involved in l-dopa turnover and tryptophan conversion in kynurenine, respectively. In conclusion, the present findings showed the efficacy of hemp water extract as a skin protective agent. This could be partly related to the extract content in cannabidiol, cannabidiolic acid and rutin.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Ybvx,

title = {Phenolic Characterization and Neuroprotective Properties of Grape Pomace Extracts},

author = {Chiavaroli A and Balaha M and Acquaviva A and Ferrante C and Cataldi A and Menghini L and Rapino M and Orlando G and Brunetti L and Leone S and Recinella L and di Giacomo V},

url = {https://www.mdpi.com/1420-3049/26/20/6216},

doi = {10.3390/molecules26206216},

year  = {2021},

date = {2021-10-28},

journal = {Molecules},

volume = {26},

number = {20},

pages = {6216},

abstract = {Vitis vinifera (grape) contains various compounds with acknowledged phytochemical and pharmacological properties. Among the different parts of the plant, pomace is of particular interest as a winemaking industry by-product. A characterization of the water extract from grape pomace from Montepulciano d'Abruzzo variety (Villamagna doc) was conducted, and the bioactive phenolic compounds were quantified through HPLC-DAD-MS analysis. HypoE22, a hypothalamic cell line, was challenged with an oxidative stimulus and exposed to different concentrations (1 µg/mL-1 mg/mL) of the pomace extract for 24, 48, and 72 h. In the same conditions, cells were exposed to the sole catechin, in a concentration range (5-500 ng/mL) consistent with the catechin level in the extract. Cell proliferation was investigated by MTT assay, dopamine release through HPLC-EC method, PGE2 amount by an ELISA kit, and expressions of neurotrophin brain-derived neurotrophic factor (BDNF) and of cyclooxygenase-2 (COX-2) by RT-PCR. The extract reverted the cytotoxicity exerted by the oxidative stimulus at all the experimental times in a dose-dependent manner, whereas the catechin was able to revert the oxidative stress-induced depletion of dopamine 48 h and 72 h after the stimulus. The extract and the catechin were also effective in preventing the downregulation of BDNF and the concomitant upregulation of COX-2 gene expression. In accordance, PGE2 release was augmented by the oxidative stress conditions and reverted by the administration of the water extract from grace pomace and catechin, which were equally effective. These results suggest that the neuroprotection induced by the extract could be ascribed, albeit partially, to its catechin content.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Ybv,

title = {Selective Inhibitors of the Inducible Nitric Oxide Synthase as Modulators of Cell Responses in LPS-Stimulated Human Monocytes},

author = {Gallorini M and Rapino M and Schweikl H and Cataldi A and Amoroso R and Maccallini C},

url = {https://www.mdpi.com/1420-3049/26/15/4419},

doi = {10.3390/molecules26154419},

year  = {2021},

date = {2021-08-25},

journal = {Molecules},

volume = {26},

number = {15},

pages = {4419},

abstract = {Inducible nitric oxide synthase (iNOS) is a crucial enzyme involved in monocyte cell response towards inflammation, and it is responsible for the production of sustained amounts of nitric oxide. This free radical molecule is involved in the defense against pathogens; nevertheless, its continuous and dysregulated production contributes to the development of several pathological conditions, including inflammatory and autoimmune diseases. In the present study, we investigated the effects of two new iNOS inhibitors, i.e., 4-(ethanimidoylamino)-N-(4-fluorophenyl)benzamide hydrobromide (FAB1020) and N-{3-[(ethanimidoylamino)methyl]benzyl}-l-prolinamidedihydrochloride (CM554), on human LPS-stimulated monocytes, using the 1400 W compound as a comparison. Our results show that CM544 and FAB1020 are selective and decrease cytotoxicity, IL-6 secretion and LPS-stimulated monocyte migration. Furthermore, the modulation of iNOS, nitrotyrosine and Nrf2 were analyzed at the protein level. Based on the collected preliminary results, the promising therapeutic value of the investigated compounds emerges, as they appear able to modulate the pro-inflammatory LPS-stimulated response in the low micromolar range in human monocytes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_445,

title = {Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes},

author = {{di Giacomo V} and Chiavaroli A and Recinella L and Orlando G and Cataldi A and Rapino M and Di Valerio V and Ronci M and Leone S and Brunetti L and Menghini L and Zengin G and Ak G and Abdallah HH and Ferrante C},

url = {https://www.mdpi.com/1422-0067/21/10/3575},

doi = {10.3390/ijms21103575 },

year  = {2020},

date = {2020-01-01},

journal = {International journal of molecular sciences},

volume = {21},

number = {10},

pages = {3575},

abstract = {Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD's effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_470,

title = {Multidirectional Pharma-Toxicological Study on Harpagophytum procumbens DC. ex Meisn.: An IBD-Focused Investigation.},

author = {Recinella L and Chiavaroli A and Ronci M and Menghini L and Brunetti L and Leone S and Tirillini B and Angelini P and Covino S and Venanzoni R and Zengin G and Di Simone S and Ciferri MC and di Giacomo V and Cataldi A and Rapino M and Valerio VD and Orlando G and Ferrante C},

url = {https://www.mdpi.com/2076-3921/9/2/168},

doi = {10.3390/antiox9020168},

year  = {2020},

date = {2020-01-01},

journal = {Antioxidants},

volume = {9},

number = {2},

pages = {e168},

abstract = {In the present study, we investigated the water extract of Harpagophytum procumbens DC. ex Meisn. in an experimental model of inflammatory bowel diseases (IBDs). Additionally, a microbiological investigation was carried out to discriminate the efficacy against bacterial and fungal strains involved in IBDs. Finally, an untargeted proteomic analysis was conducted on more than one hundred colon proteins involved in tissue morphology and metabolism. The extract was effective in blunting the production of oxidative stress and inflammation, including serotonin, prostaglandins, cytokines, and transcription factors. Additionally, the extract inhibited the growth of Candida albicans and C. tropicalis. The extract was also able to exert a pro-homeostatic effect on the levels of a wide plethora of colon proteins, thus corroborating a protective effect. Conversely, the supraphysiological downregulation of cytoskeletal-related proteins involved in tissue morphology and antimicrobial barrier function suggests a warning in the use of food supplements containing H. procumbens extracts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_444,

title = {Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus.},

author = {{di Giacomo V} and Chiavaroli A and Orlando G and Cataldi A and Rapino M and {Di Valerio V} and Leone S and Brunetti L and Menghini L and Recinella L and Ferrante C},

url = {https://www.mdpi.com/2076-3921/9/1/71},

doi = {10.3390/antiox9010071},

year  = {2020},

date = {2020-01-01},

journal = {Antioxidants},

volume = {9},

number = {1},

abstract = {Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite although there are no studies elucidating their role in the hypothalamic appetite-regulating network. Consequently, the aim of the present research is to investigate the role of CBD and CBG in regulating hypothalamic neuromodulators. Comparative evaluations between oxidative stress and food intake-modulating mediators were also performed. METHODS: Rat hypothalamic Hypo-E22 cells and isolated tissues were exposed to either CBD or CBG, and the gene expressions of neuropeptide (NP)Y, pro-opiomelanocortin (POMC) and fatty acid amide hydrolase were assessed. In parallel, the influence of CBD on the synthesis and release of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) was evaluated. The 3-hydroxykinurenine/kinurenic acid (3-HK/KA) ratio was also determined. RESULTS: Both CBD and CBG inhibited NPY and POMC gene expression and decreased the 3-HK/KA ratio in the hypothalamus. The same compounds also reduced hypothalamic NE synthesis and DA release, whereas the sole CBD inhibited 5-HT synthesis. CONCLUSION: The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_93,

title = {Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus.},

author = {{di Giacomo V} and Chiavaroli A and Orlando G and Cataldi A and Rapino M and Di Valerio V and Leone S and Brunetti L and Menghini L and Recinella L and Ferrante C},

url = {https://www.mdpi.com/2076-3921/9/1/71},

doi = {10.3390/antiox9010071},

year  = {2020},

date = {2020-01-13},

journal = {Antioxidants},

volume = {9},

number = {1},

pages = {e71},

abstract = {Cannabidiol (CBD) and cannabigerol (CBG) are non-psychotropic terpenophenols isolated from Cannabis sativa, which, besides their anti-inflammatory/antioxidant effects, are able to inhibit, the first, and to stimulate, the second, the appetite although there are no studies elucidating their role in the hypothalamic appetite-regulating network. Consequently, the aim of the present research is to investigate the role of CBD and CBG in regulating hypothalamic neuromodulators. Comparative evaluations between oxidative stress and food intake-modulating mediators were also performed. METHODS: Rat hypothalamic Hypo-E22 cells and isolated tissues were exposed to either CBD or CBG, and the gene expressions of neuropeptide (NP)Y, pro-opiomelanocortin (POMC) and fatty acid amide hydrolase were assessed. In parallel, the influence of CBD on the synthesis and release of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) was evaluated. The 3-hydroxykinurenine/kinurenic acid (3-HK/KA) ratio was also determined. RESULTS: Both CBD and CBG inhibited NPY and POMC gene expression and decreased the 3-HK/KA ratio in the hypothalamus. The same compounds also reduced hypothalamic NE synthesis and DA release, whereas the sole CBD inhibited 5-HT synthesis. CONCLUSION: The CBD modulates hypothalamic neuromodulators consistently with its anorexigenic role, whereas the CBG effect on the same mediators suggests alternative mechanisms, possibly involving peripheral pathways.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_51,

title = {Chitlac-coated Thermosets Enhance Osteogenesis and Angiogenesis in a Co-culture of Dental Pulp Stem Cells and Endothelial Cells.},

author = {Rapino M and Di Valerio V and Zara S and Gallorini M and Marconi GD and Sancilio S and Marsich E and Ghinassi B and di Giacomo V and Cataldi A},

url = {https://www.mdpi.com/2079-4991/9/7/928},

doi = {10.3390/nano9070928},

year  = {2019},

date = {2019-02-21},

journal = {Nanomaterials},

volume = {9},

number = {7},

pages = {pii: E928},

abstract = {Dental pulp stem cells (DPSCs) represent a population of stem cells which could be useful in oral and maxillofacial reconstruction. They are part of the periendothelial niche, where their crosstalk with endothelial cells is crucial in the cellular response to biomaterials used for dental restorations. DPSCs and the endothelial cell line EA.hy926 were co-cultured in the presence of Chitlac-coated thermosets in culture conditions inducing, in turn, osteogenic or angiogenic differentiation. Cell proliferation was evaluated by 3-[4,5-dimethyl-thiazol-2-yl-]-2,5-diphenyl tetrazolium bromide (MTT) assay. DPSC differentiation was assessed by measuring Alkaline Phosphtase (ALP) activity and Alizarin Red S staining, while the formation of new vessels was monitored by optical microscopy. The IL-6 and PGE2 production was evaluated as well. When cultured together, the proliferation is increased, as is the DPSC osteogenic differentiation and EA.hy926 vessel formation. The presence of thermosets appears either not to disturb the system balance or even to improve the osteogenic and angiogenic differentiation. Chitlac-coated thermosets confirm their biocompatibility in the present co-culture model, being capable of improving the differentiation of both cell types. Furthermore, the assessed co-culture appears to be a useful tool to investigate cell response toward newly synthesized or commercially available biomaterials, as well as to evaluate their engraftment potential in restorative dentistry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_30,

title = {Multiple pharmacological and toxicological investigations on Tanacetum parthenium and Salix alba extracts: Focus on potential application as anti-migraine agents.},

author = {{di Giacomo V} and Ferrante C and Ronci M and Cataldi A and Di Valerio V and Rapino M and Recinella L and Chiavaroli A and Leone S and Vladimir-Knežević S and Kindl M and Brunetti L and Menghini L and Orlando G},

url = {https://www.sciencedirect.com/science/article/pii/S0278691519305733?via%3Dihub},

doi = {10.1016/j.fct.2019.110783},

year  = {2019},

date = {2019-11-30},

journal = {Food and chemical toxicology},

volume = {133},

pages = {110783},

abstract = {Migraine is one of the most common neurological disorder, which has long been related to brain serotonin (5-HT) depletion and neuro-inflammation. Despite many treatment options are available, the frequent occurrence of unacceptable adverse effects further supports the research toward nutraceuticals and herbal preparations, among which Tanacetum parthenium and Salix alba showed promising anti-inflammatory and neuro-modulatory activities. The impact of extract treatment on astrocyte viability, spontaneous migration and apoptosis was evaluated. Anti-inflammatory/anti-oxidant effects were investigated on isolated rat cortexes exposed to a neurotoxic stimulus. The lactate dehydrogenase (LDH) release, nitrite levels and 5-HT turnover were evaluated, as well. A proteomic analysis was focused on specific neuronal proteins and a fingerprint analysis was carried out on selected phenolic compounds. Both extracts appeared able to exert in vitro anti-oxidant and anti-apoptotic effects. S. alba and T. parthenium extracts reduced LDH release, nitrite levels and 5-HT turnover induced by neurotoxic stimulus. The downregulation of selected proteins suggest a neurotoxicity, which could be ascribed to an elevated content of gallic acid in both S. alba and T. parthenium extracts. Concluding, both extracts exert neuroprotective effects, although the downregulation of key proteins involved in neuron physiology suggest caution in their use as food supplements.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_240,

title = {Effect of MRJF4 on C6 Glioma Cells Proliferation and Migration.},

author = {Pacella S and Fiorito J and Cacciatore I and di Giacomo V and Patruno A and Rapino M and Di Stefano A and Marinelli L and Fornasari E and Cataldi A and Prezzavento O and Marrazzo A},

url = {http://www.eurekaselect.com/145013/article},

doi = {10.2174/1871524916666160823122712 },

year  = {2017},

date = {2017-02-15},

journal = {Central nervous system agents in medicinal chemistry},

volume = {17},

number = {2},

pages = {129-134},

abstract = {BACKGROUND: MRJF4, a novel haloperidol metabolite II prodrug, was obtained through the esterification of the secondary hydroxyl group of haloperidol metabolite II with 4-phenylbutyric acid. The activities of (+/-)-MRJF4 and its two enantiomers [(+)-MRJF4 and (-)-MRJF4] as tumor specific inducers of pro-apoptotic genes were evaluated on malignant C6 glioma cells. In particular, changes in Nf-kB signaling pathway, activity of nitric oxide synthases (NOS), metalloproteinases (MMPs), and membrane adhesion proteins were investigated. RESULTS: IkBα reduced phosphorylation and iNOS lowered activity could be correlated with the previously demonstrated decreased proliferation and tumor progression of C6 cells upon 24 h of treatment with all the three compounds. Integrin beta1 decreased expression, at the same experimental time, seems to support lower C6 cells migrative capability and the consequent reduced invasiveness of these cells upon treatment with (+/-)-MRJF4 and its enantiomers. CONCLUSIONS: These results suggest that this multi-target prodrug and its two enantiomers might be a valuable clinical tool for the treatment of metastatic glioblastoma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_281,

title = {Cell-protection mechanism through autophagy in HGFs/S. mitis co-culture treated with Chitlac-nAg.},

author = {Gallorini M and di Giacomo V and Di Valerio V and Rapino M and Bosco D and Travan A and Di Giulio M and Di Pietro R and Paoletti S and Cataldi A and Sancilio S},

url = {http://link.springer.com/article/10.1007%2Fs10856-016-5803-5},

doi = {10.1007/s10856-016-5803-5},

year  = {2016},

date = {2016-02-18},

journal = {Journal of Materials Science. Materials in Medicine.},

volume = {27},

number = {12},

pages = {186},

abstract = {Silver-based products have been proven to be effective in retarding and preventing bacterial growth since ancient times. In the field of restorative dentistry, the use of silver ions/nanoparticles has been explored to counteract bacterial infections, as silver can destroy bacterial cell walls by reacting with membrane proteins. However, it is also cytotoxic towards eukaryotic cells, which are capable of internalizing nanoparticles. In this work, we investigated the biological effects of Chitlac-nAg, a colloidal system based on a modified chitosan (Chitlac), administered for 24-48 h to a co-culture of primary human gingival fibroblasts and Streptococcus mitis in the presence of saliva, developed to mimic the microenvironment of the oral cavity. We sought to determine its efficiency to combat oral hygiene-related diseases without affecting eukaryotic cells. Cytotoxicity, reactive oxygen species production, apoptosis induction, nanoparticles uptake, and lysosome and autophagosome metabolism were evaluated. In vitro results show that Chitlac-nAg does not exert cytotoxic effects on human gingival fibroblasts, which seem to survive through a homoeostasis mechanism involving autophagy. That suggests that the novel biomaterial Chitlac-nAg could be a promising tool in the field of dentistry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_267,

title = {Involvement of cyclic-nucleotide response element-binding family members in the radiation response of Ramos B lymphoma cells.},

author = {{Di Nisio C} and Sancilio S and Di Giacomo V and Rapino M and Sancillo L and Genovesi D and Di Siena A and Rana RA and Cataldi A and Di Pietro R},

url = {http://www.spandidos-publications.com/ijo/48/1/28},

doi = {10.3892/ijo.2015.3238},

year  = {2016},

date = {2016-01-28},

journal = {International Journal of Oncology},

volume = {48},

number = {1},

abstract = {The aim of the present study was to investigate the role of Cyclic-nucleotide Response Element-Binding (CREB) family members and related nuclear transcription factors in the radiation response of human B lymphoma cell lines (Daudi and Ramos). Unlike the more radiosensitive Daudi cells, Ramos cells demonstrated only a moderate increase in early apoptosis after 3-5 Gy irradiation doses, which was detected with Annexin V/PI staining. Moreover, a significant and dose-dependent G2/M phase accumulation was observed in the same cell line at 24 h after both ionizing radiation (IR) doses. Western blot analysis showed an early increase in CREB protein expression that was still present at 3 h and more evident after 3 Gy IR in Ramos cells, along with the dose-dependent upregulation of p53 and NF-κB. These findings were consistent with real-time RT-PCR analysis that showed an early- and dose-dependent upregulation of NFKB1, IKBKB and XIAP gene expression. Unexpectedly, pre-treatment with SN50 did not increase cell death, but cell viability. Taken together, these findings let us hypothesise that the early induction and activation of NF-κB1 in Ramos cells could mediate necrotic cell death and be linked to other molecules belonging to CREB family and involved in the cell cycle regulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_328,

title = {A dual role for beta1 integrin in an in vitro Streptococcus mitis/human gingival fibroblasts co-culture model in response to TEGDMA.},

author = {{Di Nisio C} and {De Colli M} and {di Giacomo V} and Rapino M and {Di Valerio V} and Marconi GD and Gallorini M and {Di Giulio} M and Cataldi A and Zara S},

doi = {10.1111/iej.12379},

year  = {2015},

date = {2015-02-19},

journal = {International Endodontic Journal},

volume = {48},

number = {9},

abstract = {AIM: To evaluate the effect of TEGDMA on human gingival fibroblasts (HGFs) in vitro co-cultured with Streptococcus mitis, focusing on the signalling pathways underlying cell tissue remodelling and inflammatory response processes. METHODOLOGY:β1 integrin expression was evaluated by means of imaging flow cytometry. The Western blot technique was used to investigate the expression of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), matrix metalloproteinase 9 (MMP9) and 3 (MMP3). RT-PCR was performed to quantify nuclear factor-kb subunits (Nf-kb1, ReLa), IkB kinase β (IkBkB), cyclooxygenase II (COX-2) and tumour necrosis factor-α (TNF-α) mRNA levels. Statistical analysis was performed using the analysis of variance (anova). RESULTS:

When HGFs are co-cultured with S. mitis, β1 integrin intensity, phosphorylated PKC (p-PKC), activated ERK (p-ERK), IkBkB mRNA level and MMP9 expression increased (for all molecules P < 0.05 HGFs versus HGFs co-cultured with S. mitis). A higher level of MMP3 in HGFs treated with TEGDMA was recorded (P < 0.05 HGFs versus HGFs exposed to TEGDMA). COX-2 inflammatory factor mRNA level appeared higher in HGFs exposed to 1 mmol L(-1) TEGDMA (P < 0.01 HGFs versus HGFs exposed to TEGDMA), whereas TNF-α gene expression was higher in HGFs co-cultured with S. mitis (P < 0.05 HGFs versus HGFs co-cultured with S. mitis).CONCLUSIONS: beta1 integrin triggered the signalling pathway, transduced by p-PKCα and involving ERK 1 and 2 and MMPs. This pathway resulted in an unbalanced equilibrium in tissue remodelling process, along with inflammatory response when HGFs are exposed to bacteria or biomaterial alone. On the contrary, the TEGDMA/S. mitis combination restored the balance between extracellular matrix deposition and degradation and prevented an inflammatory response. 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_383,

title = {MRJF4, a novel histone deacetylase inhibitor, induces p21 mediated autophagy in PC3 prostate cancer cells.},

author = {{Di Giacomo V} and {Di Valerio V} and Rapino M and Bosco D and Cacciatore I and Ciulla M and Marrazzo A and Fiorito J and Di Stefano A and Cataldi A},

url = {https://www.cellmolbiol.org/index.php/CMB/article/view/663},

year  = {2015},

date = {2015-06-08},

journal = {Cellular and Molecular Biology (Noisy-le-Grand, France) },

volume = {61},

number = {3},

abstract = {Autophagy is a cellular defense mechanism which occurs through degradation and recycling of cytoplasmic constituents and represents a caspase-independent alternative to cell death by apoptosis. It is generally accepted that the suppression of autophagy in many cancer cells is directly correlated to malignancy; hence, the control of autophagy genes could represent a target for cancer therapy. The inhibition of cell proliferation through autophagy activation could be an important mechanism for many anti-tumor drugs. Here we report the effects of a novel histone deacetylase inhibitor MRJF4 (racemic mixture) and of its two enantiomers [(+)-MRJF4 and (-)-MRJF4] on the morphological and molecular mechanisms causing death and migration of PC3 prostatic cancer cells. In particular, we investigated the occurrence of the autophagic process, both at morphological and molecular levels (LC3 expression), and its relationship with p21, a key molecule which regulates cell cycle and autophagy cell death. Moreover, pERK/Nf-kB driven intracellular signaling, the expression of MMP9 protein - a key component of cell migration - invasion, and metastasis were assayed. Our results showed that the anti-proliferative effects of MRJF4 due to autophagy occurrence, documented by LC3 increase and ultrastructural modifications, and the reduction of invasiveness seem to be mediated by the down-regulation of pERK/NF-kB signaling pathway, along with p21 up-regulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_386,

title = {NF-kB mediated down-regulation of collagen synthesis upon HEMA (2-hydroxyethyl methacrylate) treatment of primary human gingival fibroblast/Streptococcus mutans co-cultured cells.},

author = {Grande R and Pacella S and Di Giulio M and Rapino M and Di Valerio V and Cellini L and Cataldi A},

url = {https://link.springer.com/article/10.1007%2Fs00784-014-1304-4},

doi = {10.1007/s00784-014-1304-4},

year  = {2015},

date = {2015-03-25},

journal = {Clinical Oral Investigations},

volume = {19},

number = {4},

abstract = {PURPOSE: In vitro studies have evidenced the cytotoxic effect of HEMA (2-hydroxyethyl methacrylate), the most common component of dental resin-based restorative material, which is released within the oral cavity, on eukaryotic cells such as gingival fibroblast and epithelial cells. However, since the presence of microorganisms within the oral cavity cannot be excluded and little is known about the interactions occurring between eukaryotic cells and the human oral microbiota, our attention has been addressed to investigate the effect of 3 mM HEMA on the molecular mechanisms driving the response of human gingival fibroblasts (HGFs) co-cultured with Streptococcus mutans. METHODOLOGY:HGF/S. mutans co-culture has been set up in our lab, and upon HEMA treatment, S.mutans and HGF cells' viability and adhesion along with type I collagen gene and pro-collagen I, Bax, Bcl2, nuclear factor kB (NF-kB), IkBα, pIkBα protein expression by PCR, Western blotting and ELISA assays have been investigated. RESULTS:HEMA treatment determines a significant decrease of type I collagen protein production, even in the presence of S. mutans, in parallel to a decrease of cell viability and adhesion, which seem to be regulated by NF-kB activation. In fact, when SN50, NF-kB-specific pharmacological inhibitor, is added to the culture, cell proliferation along with collagen synthesis is restored. CONCLUSION: The modulation exerted by S. mutans on the cytotoxic effect of HEMA suggests that within the oral cavity, the eukaryotic/prokaryotic cell interactions, maintaining the balance of the environment, allow HEMA to perform its adhesive and bonding function and that the use of a co-culture system, which simulates the oral cavity organization, improves the knowledge concerning the biocompatibility of this dental material.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}