141 results on '"Monica Montopoli"'
Search Results
2. Rapamycin rescues mitochondrial dysfunction in cells carrying the m.8344A > G mutation in the mitochondrial tRNALys
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Mariantonietta Capristo, Valentina Del Dotto, Concetta Valentina Tropeano, Claudio Fiorini, Leonardo Caporali, Chiara La Morgia, Maria Lucia Valentino, Monica Montopoli, Valerio Carelli, and Alessandra Maresca
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MERRF ,Mitochondrial DNA ,Niacin ,PGC-1α ,Rapamycin ,mTORC1 ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Myoclonus, Epilepsy and Ragged-Red-Fibers (MERRF) is a mitochondrial encephalomyopathy due to heteroplasmic mutations in mitochondrial DNA (mtDNA) most frequently affecting the tRNA Lys gene at position m.8344A > G. Defective tRNALys severely impairs mitochondrial protein synthesis and respiratory chain when a high percentage of mutant heteroplasmy crosses the threshold for full-blown clinical phenotype. Therapy is currently limited to symptomatic management of myoclonic epilepsy, and supportive measures to counteract muscle weakness with co-factors/supplements. Methods We tested two therapeutic strategies to rescue mitochondrial function in cybrids and fibroblasts carrying different loads of the m.8344A > G mutation. The first strategy was aimed at inducing mitochondrial biogenesis directly, over-expressing the master regulator PGC-1α, or indirectly, through the treatment with nicotinic acid, a NAD+ precursor. The second was aimed at stimulating the removal of damaged mitochondria through prolonged rapamycin treatment. Results The first approach slightly increased mitochondrial protein expression and respiration in the wild type and intermediate-mutation load cells, but was ineffective in high-mutation load cell lines. This suggests that induction of mitochondrial biogenesis may not be sufficient to rescue mitochondrial dysfunction in MERRF cells with high-mutation load. The second approach, when administered chronically (4 weeks), induced a slight increase of mitochondrial respiration in fibroblasts with high-mutation load, and a significant improvement in fibroblasts with intermediate-mutation load, rescuing completely the bioenergetics defect. This effect was mediated by increased mitochondrial biogenesis, possibly related to the rapamycin-induced inhibition of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and the consequent activation of the Transcription Factor EB (TFEB). Conclusions Overall, our results point to rapamycin-based therapy as a promising therapeutic option for MERRF.
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- 2022
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3. BNIP3-dependent mitophagy role in cisplatin resistance
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Veronica Cocetta, Caterina Vianello, Marta Giacomello, and Monica Montopoli
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autophagy inhibitors ,cancer ,chemotherapy resistance ,mitochondria ,mitophagy ,Cytology ,QH573-671 - Published
- 2022
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4. Characterization of raloxifene as a potential pharmacological agent against SARS-CoV-2 and its variants
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Daniela Iaconis, Licia Bordi, Giulia Matusali, Carmine Talarico, Candida Manelfi, Maria Candida Cesta, Mara Zippoli, Francesca Caccuri, Antonella Bugatti, Alberto Zani, Federica Filippini, Laura Scorzolini, Marco Gobbi, Marten Beeg, Arianna Piotti, Monica Montopoli, Veronica Cocetta, Silvia Bressan, Enrico M. Bucci, Arnaldo Caruso, Emanuele Nicastri, Marcello Allegretti, and Andrea R. Beccari
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Cytology ,QH573-671 - Abstract
Abstract The new coronavirus SARS-CoV-2 is the causative agent of the COVID-19 pandemic, which so far has caused over 6 million deaths in 2 years, despite new vaccines and antiviral medications. Drug repurposing, an approach for the potential application of existing pharmaceutical products to new therapeutic indications, could be an effective strategy to obtain quick answers to medical emergencies. Following a virtual screening campaign on the most relevant viral proteins, we identified the drug raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a new potential agent to treat mild-to-moderate COVID-19 patients. In this paper we report a comprehensive pharmacological characterization of raloxifene in relevant in vitro models of COVID-19, specifically in Vero E6 and Calu-3 cell lines infected with SARS-CoV-2. A large panel of the most common SARS-CoV-2 variants isolated in Europe, United Kingdom, Brazil, South Africa and India was tested to demonstrate the drug’s ability in contrasting the viral cytopathic effect (CPE). Literature data support a beneficial effect by raloxifene against the viral infection due to its ability to interact with viral proteins and activate protective estrogen receptor-mediated mechanisms in the host cells. Mechanistic studies here reported confirm the significant affinity of raloxifene for the Spike protein, as predicted by in silico studies, and show that the drug treatment does not directly affect Spike/ACE2 interaction or viral internalization in infected cell lines. Interestingly, raloxifene can counteract Spike-mediated ADAM17 activation in human pulmonary cells, thus providing new insights on its mechanism of action. A clinical study in mild to moderate COVID-19 patients (NCT05172050) has been recently completed. Our contribution to evaluate raloxifene results on SARS-CoV-2 variants, and the interpretation of the mechanisms of action will be key elements to better understand the trial results, and to design new clinical studies aiming to evaluate the potential development of raloxifene in this indication.
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- 2022
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5. Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy
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Caterina Vianello, Veronica Cocetta, Daniela Catanzaro, Gerald W Dorn, Angelo De Milito, Flavio Rizzolio, Vincenzo Canzonieri, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli, Vincenzo Quagliariello, Annabella Di Mauro, Simona Losito, Nicola Maurea, Cono Scaffa, Gabriele Sales, Luca Scorrano, Marta Giacomello, and Monica Montopoli
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Cytology ,QH573-671 - Abstract
Abstract Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.
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- 2022
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6. Correction: Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy
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Caterina Vianello, Veronica Cocetta, Daniela Catanzaro, Gerald W Dorn, Angelo De Milito, Flavio Rizzolio, Vincenzo Canzonieri, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli, Vincenzo Quagliariello, Annabella Di Mauro, Simona Losito, Nicola Maurea, Cono Scaffa, Gabriele Sales, Luca Scorrano, Marta Giacomello, and Monica Montopoli
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Cytology ,QH573-671 - Published
- 2023
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7. Circulating Vitamin D Level and Its Impact on Mortality and Recurrence in Stage III Colorectal Cancer Patients: A Systematic Review and Meta-Analysis
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Alessandro Ottaiano, Sergio Facchini, Mariachiara Santorsola, Guglielmo Nasti, Gaetano Facchini, Liliana Montella, Nicola Maurea, Marco Cascella, Domenico Iervolino, Bianca Arianna Facchini, Monica Montopoli, Pierluigi Consolo, Vincenzo Quagliariello, Luca Rinaldi, and Massimiliano Berretta
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colorectal cancer ,prognosis ,vitamin D ,survival ,disease-free survival ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Vitamin D (VD) has been implicated in several diseases, including colorectal cancer (CRC). This study aimed to determine whether there is an association between VD levels and time-to-outcome in stage III CRC patients through a systematic review and meta-analysis. Methods: The study adhered to the PRISMA 2020 statement. Articles were searched in PubMed/MEDLINE and Scopus/ELSEVIER. Four articles were selected, with the primary objective of providing a pooled estimate of the risk of death specifically in stage III CRC patients based on pre-operative VD levels. Study heterogeneity and publication bias were analyzed using Tau2 statistics and funnel plots. Results: The selected studies showed significant heterogeneity regarding time-to-outcome, technical assessments, and serum VD concentration measures. The pooled analysis of 2628 and 2024 patients revealed a 38% and 13% increase in the risk of death (HR: 1.38, 95% CI: 0.71–2.71) and recurrence (HR: 1.13; 95% CI: 0.84–1.53), respectively, for random-effects models among patients with lower levels of VD. Conclusions: Our findings suggest that a low concentration of VD has a significant negative impact on time-to-outcome in stage III CRC.
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- 2023
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8. Editorial: Metabolism Meets Function: The Multifaced Role of Metabolism in Cancer
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Isabella Giacomini and Monica Montopoli
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cancer ,cancer metabolism ,tumor microenviroment (TME) ,drug resistance ,metabolic reprogramming ,targeting metabolism ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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9. Contribution of Mitochondrial Activity to Doxorubicin-Resistance in Osteosarcoma Cells
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Isabella Giacomini, Margherita Cortini, Mattia Tinazzi, Nicola Baldini, Veronica Cocetta, Eugenio Ragazzi, Sofia Avnet, and Monica Montopoli
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osteosarcoma ,cancer ,chemotherapy ,doxorubicin ,drug resistance ,metabolism ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Osteosarcoma is considered the most common bone tumor affecting children and young adults. The standard of care is chemotherapy; however, the onset of drug resistance still jeopardizes osteosarcoma patients, thus making it necessary to conduct a thorough investigation of the possible mechanisms behind this phenomenon. In the last decades, metabolic rewiring of cancer cells has been proposed as a cause of chemotherapy resistance. Our aim was to compare the mitochondrial phenotype of sensitive osteosarcoma cells (HOS and MG-63) versus their clones when continuously exposed to doxorubicin (resistant cells) and identify alterations exploitable for pharmacological approaches to overcome chemotherapy resistance. Compared with sensitive cells, doxorubicin-resistant clones showed sustained viability with less oxygen-dependent metabolisms, and significantly reduced mitochondrial membrane potential, mitochondrial mass, and ROS production. In addition, we found reduced expression of TFAM gene generally associated with mitochondrial biogenesis. Finally, combined treatment of resistant osteosarcoma cells with doxorubicin and quercetin, a known inducer of mitochondrial biogenesis, re-sensitizes the doxorubicin effect in resistant cells. Despite further investigations being needed, these results pave the way for the use of mitochondrial inducers as a promising strategy to re-sensitize doxorubicin cytotoxicity in patients who do not respond to therapy or reduce doxorubicin side effects.
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- 2023
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10. Evaluation of Concomitant Use of Anticancer Drugs and Herbal Products: From Interactions to Synergic Activity
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Massimiliano Berretta, Lissandra Dal Lago, Mattia Tinazzi, Andrea Ronchi, Gaspare La Rocca, Liliana Montella, Raffaele Di Francia, Bianca Arianna Facchini, Alessia Bignucolo, and Monica Montopoli
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complementary ,alternative ,medicine ,cancer ,chemotherapy ,interactions ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
CAM is used by about 40% of cancer patients in Western Countries, with peaks of 80% for breast cancer patients. Cancer patients use CAM to boost immune function, to control cancer symptoms and treatment-related side effects, and to improve health-related quality of life (HR-QoL) and survival. Unfortunately, self-prescription of natural remedies in cancer patients can lead to unexpected toxicities and can reduce the effectiveness of cancer therapy. Although CAM usually refers to all the “natural or organic” products/methods that are generally considered less toxic, there are concerns about drug interactions, especially in patients participating in clinical trials with experimental agents. Despite the claims of the promising and potential benefits made by prescribers, many CAMs lack clear scientific evidence of their safety and efficacy. Given the widespread use of CAM—both clearly declared and overt—in this review, we focused on the most important known data on the risk of interactions between biologics and oncology drugs with the goal of opening up CAM in accordance with the meaning of integrative medicine.
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- 2022
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11. Editorial Comment to Castration‐resistant prostate cancer diagnosed during leuprorelin treatment for spinal and bulbar muscular atrophy
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Maria Pennuto, Monica Montopoli, and Carlo Rinaldi
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2022
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12. Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression
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Vincenzo Quagliariello, Massimiliano Berretta, Simona Buccolo, Martina Iovine, Andrea Paccone, Ernesta Cavalcanti, Rosaria Taibi, Monica Montopoli, Gerardo Botti, and Nicola Maurea
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sunitinib ,polydatin ,cardio-oncology ,microenvironment ,chemokine ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Renal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. Sunitinib, a recently-approved, multi-targeted Tyrosine Kinases Inhibitor (TKi), prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. Polydatin (3,4’,5-trihydroxystilbene-3-β-d-glucoside) is a monocrystalline compound isolated from Polygonum cuspidatum with consolidated anti-oxidant and anti-inflammatory properties, however no studies investigated on its putative cardioprotective and chemosensitizing properties during incubation with sunitinib. We investigated on the effects of polydatin on the oxidative stress, NLRP3 inflammasome and Myd88 expression, highlighting on the production of cytokines and chemokines (IL-1β, IL-6, IL-8, CXCL-12 and TGF-β) during treatment with sunitinib. Exposure of cardiomyocytes and cardiomyoblasts (AC-16 and H9C2 cell lines) and human renal adenocarcinoma cells (769‐P and A498) to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly iROS, MDA and LTB4 compared to only sunitinib-treated cells (P
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- 2021
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13. Hereditary Spastic Paraplegia and Future Therapeutic Directions: Beneficial Effects of Small Compounds Acting on Cellular Stress
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Sentiljana Gumeni, Chiara Vantaggiato, Monica Montopoli, and Genny Orso
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hereditary spastic paraplegia ,rapamycin ,N-acetyl cysteine ,salubrinal ,guanabenz ,methylene blue ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative conditions that share a characteristic feature of degeneration of the longest axons within the corticospinal tract, which leads to progressive spasticity and weakness of the lower limbs. Mutations of over 70 genes produce defects in various biological pathways: axonal transport, lipid metabolism, endoplasmic reticulum (ER) shaping, mitochondrial function, and endosomal trafficking. HSPs suffer from an adequate therapeutic plan. Currently the treatments foreseen for patients affected by this pathology are physiotherapy, to maintain the outgoing tone, and muscle relaxant therapies for spasticity. Very few clinical studies have been conducted, and it’s urgent to implement preclinical animal studies devoted to pharmacological test and screening, to expand the rose of compounds potentially attractive for clinical trials. Small animal models, such as Drosophila melanogaster and zebrafish, have been generated, analyzed, and used as preclinical model for screening of compounds and their effects. In this work, we briefly described the role of HSP-linked proteins in the organization of ER endomembrane system and in the regulation of ER homeostasis and stress as a common pathological mechanism for these HSP forms. We then focused our attention on the pharmacodynamic and pharmacokinetic features of some recently identified molecules with antioxidant property, such as salubrinal, guanabenz, N-acetyl cysteine, methylene blue, rapamycin, and naringenin, and on their potential use in future clinical studies. Expanding the models and the pharmacological screening for HSP disease is necessary to give an opportunity to patients and clinicians to test new molecules.
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- 2021
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14. Cannabidiol Isolated From Cannabis sativa L. Protects Intestinal Barrier From In Vitro Inflammation and Oxidative Stress
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Veronica Cocetta, Paolo Governa, Vittoria Borgonetti, Mattia Tinazzi, Gregorio Peron, Daniela Catanzaro, Massimiliano Berretta, Marco Biagi, Fabrizio Manetti, Stefano Dall’Acqua, and Monica Montopoli
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intestinal barrier dysfunction ,Cannabis sativa ,cannabidiol ,intestinal inflammation ,transepithelial electrical resistance ,intestinal permeability ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The relevance and incidence of intestinal bowel diseases (IBD) have been increasing over the last 50 years and the current therapies are characterized by severe side effects, making essential the development of new strategies that combine efficacy and safety in the management of human IBD. Herbal products are highly considered in research aimed at discovering new approaches for IBD therapy and, among others, Cannabis sativa L. has been traditionally used for centuries as an analgesic and anti-inflammatory remedy also in different gastrointestinal disorders. This study aims to investigate the effects of different C. sativa isolated compounds in an in vitro model of intestinal epithelium. The ability of treatments to modulate markers of intestinal dysfunctions was tested on Caco-2 intestinal cell monolayers. Our results, obtained by evaluation of ROS production, TEER and paracellular permeability measurements and tight junctions evaluation show Cannabidiol as the most promising compound against intestinal inflammatory condition. Cannabidiol is able to inhibit ROS production and restore epithelial permeability during inflammatory and oxidative stress conditions, suggesting its possible application as adjuvant in IBD management.
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- 2021
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15. The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies
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Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, and Monica Montopoli
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vitamin D ,calcium homeostasis ,cancer ,immune system ,infectious disease ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Vitamin D exerts multiple beneficial effects in humans, including neuronal, immune, and bone homeostasis and the regulation of cardiovascular functions. Recent studies correlate vitamin D with cancer cell growth and survival, but meta-analyses on this topic are often not consistent. Methods: A systematic search of the PubMed database and the Clinical Trial Register was performed to identify all potentially relevant English-language scientific papers containing original research articles on the effects of vitamin D on human health. Results: In this review, we analyzed the antioxidant and anti-inflammatory effects of vitamin D against acute and chronic diseases, focusing particularly on cancer, immune-related diseases, cardiomyophaties (including heart failure, cardiac arrhythmias, and atherosclerosis) and infectious diseases. Conclusions: Vitamin D significantly reduces the pro-oxidant systemic and tissue biomarkers involved in the development, progression, and recurrence of chronic cardiometabolic disease and cancer. The overall picture of this review provides the basis for new randomized controlled trials of oral vitamin D supplementation in patients with cancer and infectious, neurodegenerative, and cardiovascular diseases aimed at reducing risk factors for disease recurrence and improving quality of life.
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- 2022
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16. Correction: Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy
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Caterina Vianello, Veronica Cocetta, Daniela Catanzaro, Gerald W Dorn, Angelo De Milito, Flavio Rizzolio, Vincenzo Canzonieri, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli, Vincenzo Quagliariello, Annabella Di Mauro, Simona Losito, Nicola Maurea, Cono Scaffa, Gabriele Sales, Luca Scorrano, Marta Giacomello, and Monica Montopoli
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Cytology ,QH573-671 - Published
- 2022
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17. Metabolic Plasticity in Chemotherapy Resistance
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Maria Andrea Desbats, Isabella Giacomini, Tommaso Prayer-Galetti, and Monica Montopoli
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cancer ,metabolic reprogramming ,TCA cycle ,Warburg effect ,metabolic vulnerabilities ,chemoresistance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Resistance of cancer cells to chemotherapy is the first cause of cancer-associated death. Thus, new strategies to deal with the evasion of drug response and to improve clinical outcomes are needed. Genetic and epigenetic mechanisms associated with uncontrolled cell growth result in metabolism reprogramming. Cancer cells enhance anabolic pathways and acquire the ability to use different carbon sources besides glucose. An oxygen and nutrient-poor tumor microenvironment determines metabolic interactions among normal cells, cancer cells and the immune system giving rise to metabolically heterogeneous tumors which will partially respond to metabolic therapy. Here we go into the best-known cancer metabolic profiles and discuss several studies that reported tumors sensitization to chemotherapy by modulating metabolic pathways. Uncovering metabolic dependencies across different chemotherapy treatments could help to rationalize the use of metabolic modulators to overcome therapy resistance.
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- 2020
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18. Haplogroup J mitogenomes are the most sensitive to the pesticide rotenone: Relevance for human diseases
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Daniela Strobbe, Leonardo Caporali, Luisa Iommarini, Alessandra Maresca, Monica Montopoli, Andrea Martinuzzi, Alessandro Achilli, Anna Olivieri, Antonio Torroni, Valerio Carelli, and Anna Ghelli
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Rotenone ,Cybrids ,Mitochondrial DNA ,Haplogroups ,Complex I ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
There is growing evidence that the sequence variation of mitochondrial DNA (mtDNA), which clusters in population- and/or geographic-specific haplogroups, may result in functional effects that, in turn, become relevant in disease predisposition or protection, interaction with environmental factors and ultimately in modulating longevity.To unravel functional differences between mtDNA haplogroups we here employed transmitochondrial cytoplasmic hybrid cells (cybrids) grown in galactose medium, a culture condition that forces oxidative phosphorylation, and in the presence of rotenone, the classic inhibitor of respiratory Complex I. Under this experimental paradigm we assessed functional parameters such as cell viability and respiration, ATP synthesis, reactive oxygen species production and mtDNA copy number.Our analyses show that haplogroup J1, which is common in western Eurasian populations, is the most sensitive to rotenone, whereas K1 mitogenomes orchestrate the best compensation, possibly because of the haplogroup-specific missense variants impinging on Complex I function. Remarkably, haplogroups J1 and K1 fit the genetic associations previously established with Leber's hereditary optic neuropathy (LHON) for J1, as a penetrance enhancer, and with Parkinson's disease (PD) for K1, as a protective background.Our findings provide functional evidences supporting previous well-established genetic associations of specific haplogroups with two neurodegenerative pathologies, LHON and PD. Our experimental paradigm is instrumental to highlighting the subtle functional differences characterizing mtDNA haplogroups, which will be increasingly needed to dissect the role of mtDNA genetic variation in health, disease and longevity.
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- 2018
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19. Chemotherapy-Induced Hepatotoxicity in HIV Patients
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Silvia Bressan, Alessandra Pierantoni, Saman Sharifi, Sergio Facchini, Vincenzo Quagliariello, Massimiliano Berretta, and Monica Montopoli
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drug-drug interactions ,hepatotoxicity ,HIV ,ART ,chemotherapy ,immunotherapy ,Cytology ,QH573-671 - Abstract
Human immunodeficiency virus (HIV) affects more than 37 million people globally, and in 2020, more than 680,000 people died from HIV-related causes. Recently, these numbers have decrease substantially and continue to reduce thanks to the use of antiretroviral therapy (ART), thus making HIV a chronic disease state for those dependent on lifelong use of ART. However, patients with HIV have an increased risk of developing some type of cancer compared to patients without HIV. Therefore, treatment of patients who are diagnosed with both HIV and cancer represents a complicated scenario because of the risk associated with drug–drug interaction (DDIs) and related toxicity. Selection of an alternative chemotherapy or ART or temporarily discontinuation of ART constitute a strategy to manage the risk of DDIs. Temporarily withholding ART is the less desirable clinical plan but risks and benefits must be considered in each scenario. In this review we focus on the hepatotoxicity associated with a simultaneous treatment with ART and chemotherapeutic drugs and mechanisms behind. Moreover, we also discuss the effect on the liver caused by the association of immunotherapeutic drugs, which have recently been used in clinical trials and also in HIV patients.
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- 2021
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20. Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives
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Veronica Cocetta, Vincenzo Quagliariello, Francesco Fiorica, Massimiliano Berretta, and Monica Montopoli
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resveratrol ,chemosensitization ,chemotherapy resistance ,cancer ,drug resistance ,integrative medicine ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.
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- 2021
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21. Serenoa repens and Urtica dioica Fixed Combination: In-Vitro Validation of a Therapy for Benign Prostatic Hyperplasia (BPH)
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Miriam Saponaro, Isabella Giacomini, Giulia Morandin, Veronica Cocetta, Eugenio Ragazzi, Genny Orso, Ilaria Carnevali, Massimiliano Berretta, Mariangela Mancini, Francesco Pagano, and Monica Montopoli
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BPH ,inflammation ,oxidative stress ,Serenoa repens ,Urtica dioica ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.
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- 2020
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22. Multiple Effects of Ascorbic Acid against Chronic Diseases: Updated Evidence from Preclinical and Clinical Studies
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Massimiliano Berretta, Vincenzo Quagliariello, Nicola Maurea, Raffaele Di Francia, Saman Sharifi, Gaetano Facchini, Luca Rinaldi, Michela Piezzo, Ceccarelli Manuela, Giuseppe Nunnari, and Monica Montopoli
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ASC ,antioxidant ,cancer ,immune system ,cardiovascular diseases ,infectious diseases ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Severe disease commonly manifests as a systemic inflammatory process. Inflammation is associated withthe enhanced production of reactive oxygen and nitrogen species and with a marked reduction in the plasma concentrations of protective antioxidant molecules. This imbalance gives rise to oxidative stress, which is greater in patients with more severe conditions such as sepsis, cancer, cardiovascular disease, acute respiratory distress syndrome, and burns. In these patients, oxidative stress can trigger cell, tissue, and organ damage, thus increasing morbidity and mortality. Ascorbic acid (ASC) is a key nutrient thatserves as an antioxidant and a cofactor for numerous enzymatic reactions. However, humans, unlike most mammals, are unable to synthesize it. Consequently, ASC must be obtained through dietary sources, especially fresh fruit and vegetables. The value of administering exogenous micronutrients, to reestablish antioxidant concentrations in patients with severe disease, has been recognized for decades. Despite the suggestion that ASC supplementation may reduce oxidative stress and prevent several chronic conditions, few large, randomized clinical trials have tested it in patients with severe illness. This article reviews the recent literature on the pharmacological profile of ASC and the role of its supplementation in critically ill patients.
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- 2020
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23. The Bladder EpiCheck Test as a Non-Invasive Tool Based on the Identification of DNA Methylation in Bladder Cancer Cells in the Urine: A Review of Published Evidence
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Mariangela Mancini, Marialaura Righetto, Sara Zumerle, Monica Montopoli, and Filiberto Zattoni
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bladder cancer ,DNA methylation ,biomarkers ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Recently, there has been a great effort to develop tests based on non-invasive urinary biomarkers (NMIBCs). These tests are based on the fact that NMIBCs are heterogeneous at the molecular level and can be divided into different molecular groups useful to predict prognosis and response to treatment. The assessment of epigenetic alterations, such as DNA methylation, represents a promising cancer biomarker. DNA methylation is an epigenetic modification that affects gene expression without modifying the DNA sequence. Several studies have highlighted the presence of methylated loci in the context of bladder cancer, indicating its potential application as a diagnostic and prognostic biomarker. One of the novel assays based on a DNA methylation profile, the Bladder EpiCheck, analyzes DNA from spontaneous urine, detecting disease-specific DNA methylation patterns in bladder cancer patients. This test, due to its non-invasive nature and highly promising performance could, in future, become an invaluable tool in the follow-up of bladder cancer patients. Potential new applications could include diagnosis and surveillance of upper-tract disease, for the replacement of invasive testing and ureteroscopy.
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- 2020
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24. The Pentose Phosphate Pathway and Its Involvement in Cisplatin Resistance
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Isabella Giacomini, Eugenio Ragazzi, Gianfranco Pasut, and Monica Montopoli
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cisplatin ,pentose phosphate pathway ,cancer ,resistance ,drug delivery systems ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Cisplatin is the first-line treatment for different types of solid tumors, such as ovarian, testicular, bladder, cervical, head and neck, lung, and esophageal cancers. The main problem related to its clinical use is the onset of drug resistance. In the last decades, among the studied molecular mechanisms of cisplatin resistance, metabolic reprogramming has emerged as a possible one. This review focuses on the pentose phosphate pathway (PPP) playing a pivotal role in maintaining the high cell proliferation rate and representing an advantage for cancer cells. In particular, the oxidative branch of PPP plays a role in oxidative stress and seems to be involved in cisplatin resistance. In light of these considerations, it has been demonstrated that overexpression and higher enzymatic activity of different enzymes of both oxidative and non-oxidative branches (such as glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and transketolase) increase cisplatin resistance, and their silencing or combined treatment with cisplatin could restore cisplatin sensitivity. Moreover, drug delivery systems loaded with both PPP inhibitors and cisplatin give the possibility of reaching cancer cells selectively. In conclusion, targeting PPP is becoming a strategy to overcome cisplatin resistance; however, further studies are required to better understand the mechanisms.
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- 2020
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25. Peculiar combinations of individually non-pathogenic missense mitochondrial DNA variants cause low penetrance Leber's hereditary optic neuropathy.
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Leonardo Caporali, Luisa Iommarini, Chiara La Morgia, Anna Olivieri, Alessandro Achilli, Alessandra Maresca, Maria Lucia Valentino, Mariantonietta Capristo, Francesca Tagliavini, Valentina Del Dotto, Claudia Zanna, Rocco Liguori, Piero Barboni, Michele Carbonelli, Veronica Cocetta, Monica Montopoli, Andrea Martinuzzi, Giovanna Cenacchi, Giuseppe De Michele, Francesco Testa, Anna Nesti, Francesca Simonelli, Anna Maria Porcelli, Antonio Torroni, and Valerio Carelli
- Subjects
Genetics ,QH426-470 - Abstract
We here report on the existence of Leber's hereditary optic neuropathy (LHON) associated with peculiar combinations of individually non-pathogenic missense mitochondrial DNA (mtDNA) variants, affecting the MT-ND4, MT-ND4L and MT-ND6 subunit genes of Complex I. The pathogenic potential of these mtDNA haplotypes is supported by multiple evidences: first, the LHON phenotype is strictly inherited along the maternal line in one very large family; second, the combinations of mtDNA variants are unique to the two maternal lineages that are characterized by recurrence of LHON; third, the Complex I-dependent respiratory and oxidative phosphorylation defect is co-transferred from the proband's fibroblasts into the cybrid cell model. Finally, all but one of these missense mtDNA variants cluster along the same predicted fourth E-channel deputed to proton translocation within the transmembrane domain of Complex I, involving the ND1, ND4L and ND6 subunits. Hence, the definition of the pathogenic role of a specific mtDNA mutation becomes blurrier than ever and only an accurate evaluation of mitogenome sequence variation data from the general population, combined with functional analyses using the cybrid cell model, may lead to final validation. Our study conclusively shows that even in the absence of a clearly established LHON primary mutation, unprecedented combinations of missense mtDNA variants, individually known as polymorphisms, may lead to reduced OXPHOS efficiency sufficient to trigger LHON. In this context, we introduce a new diagnostic perspective that implies the complete sequence analysis of mitogenomes in LHON as mandatory gold standard diagnostic approach.
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- 2018
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26. Mitochondrial Involvement in Cisplatin Resistance
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Veronica Cocetta, Eugenio Ragazzi, and Monica Montopoli
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mitochondria ,cisplatin ,resistance ,mitochondrial dynamics ,mtDNA ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.
- Published
- 2019
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27. Effects of Boswellia Serrata Roxb. and Curcuma longa L. in an In Vitro Intestinal Inflammation Model Using Immune Cells and Caco-2
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Paolo Governa, Maddalena Marchi, Veronica Cocetta, Bianca De Leo, Philippa T. K. Saunders, Daniela Catanzaro, Elisabetta Miraldi, Monica Montopoli, and Marco Biagi
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Boswellia serrata Roxb. ,Curcuma longa L. ,intestinal bowel diseases (IBD) ,Caco-2 ,PBMC ,HMC-1.1 ,mast cells ,cytokines ,trans epithelial electrical resistance (TEER) ,reactive oxygen species (ROS) ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favourable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/mL, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H2O2-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.
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- 2018
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28. Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage.
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Daniela Catanzaro, Serena Rancan, Genny Orso, Stefano Dall'Acqua, Paola Brun, Maria Cecilia Giron, Maria Carrara, Ignazio Castagliuolo, Eugenio Ragazzi, Laura Caparrotta, and Monica Montopoli
- Subjects
Medicine ,Science - Abstract
Aminosalicylates, corticosteroids and immunosuppressants are currently the therapeutic choices in inflammatory bowel diseases (IBD), however, with limited remission and often serious side effects. Meanwhile complementary and alternative medicine (CAM) use is increasing, particularly herbal medicine. Boswellia serrata is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest for its usefulness in IBDs. The mechanism of this pharmacological potential of Boswellia serrata was investigated in colonic epithelial cell monolayers exposed to H2O2 or INF-γ+TNF-α, chosen as in vitro experimental model of intestinal inflammation. The barrier function was evaluated by the transepithelial electrical resistance (TEER) and paracellular permeability assay, and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin) immunofluorescence. The expression of phosphorylated NF-κB and reactive oxygen species (ROS) generation were determined by immunoblot and cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE) and its pure derivative acetyl-11-keto-β-boswellic acid (AKBA), were tested at 0.1-10 μg/ml and 0.027 μg/ml, respectively. BSE and AKBA safety was demonstrated by no alteration of intestinal cell viability and barrier function and integrity biomarkers. H2O2 or INF-γ+TNF-α treatment of Caco-2 cell monolayers significantly reduced TEER, increased paracellular permeability and caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA pretreatment significantly prevented functional and morphological alterations and also the NF-κB phosphorylation induced by the inflammatory stimuli. At the same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2 exposure. Data showed the positive correlation of the antioxidant activity with the mechanism involved in the physiologic maintenance of the integrity and function of the intestinal epithelium. This study elucidates the pharmacological mechanisms mediated by BSE, in protecting intestinal epithelial barrier from inflammatory damage and supports its use as safe adjuvant in patients affected by IBD.
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- 2015
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29. Human Adenocarcinoma Cell Line Sensitivity to Essential Oil Phytocomplexes from Pistacia Species: a Multivariate Approach
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Alessandro Buriani, Stefano Fortinguerra, Vincenzo Sorrenti, Stefano Dall’Acqua, Gabbriella Innocenti, Monica Montopoli, Daniela Gabbia, and Maria Carrara
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Pistacia ,terpenes ,cytotoxic ,principal component analysis ,Organic chemistry ,QD241-441 - Abstract
Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus, P. lentiscus var. chia (mastic gum), P. terebinthus, P. vera, and P. integerrima, was screened on three human adenocarcinoma cell lines: MCF-7 (breast), 2008 (ovarian), and LoVo (colon). The results indicate that all the Pistacia phytocomplexes, with the exception of mastic gum oil, induce cytotoxic effects on one or more of the three cell lines. PCA highlighted the presence of different cooperating clusters of bioactive molecules. Cluster variability among species, and even within the same species, could explain some of the differences seen among samples suggesting the presence of both common and species-specific mechanisms. Single molecules from one of the most significant clusters were tested, but only bornyl-acetate presented cytotoxic activity, although at much higher concentrations (IC50 = 138.5 µg/mL) than those present in the essential oils, indicating that understanding of the full biological effect requires a holistic vision of the phytocomplexes with all its constituents.
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- 2017
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30. Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through <scp>CB2</scp> receptors‐, endocannabinoids‐, and <scp>NF‐κB</scp> ‐mediated signaling
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Vittoria Borgonetti, Cristina Benatti, Paolo Governa, Giovanni Isoldi, Federica Pellati, Silvia Alboni, Fabio Tascedda, Monica Montopoli, Nicoletta Galeotti, Fabrizio Manetti, Elisabetta Miraldi, Marco Biagi, and Giovanna Rigillo
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Pharmacology - Published
- 2022
31. Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer
- Author
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Nicolò Bancaro, Bianca Calì, Martina Troiani, Angela Rita Elia, Rydell Alvarez Arzola, Giuseppe Attanasio, Ping Lai, Mateus Crespo, Bora Gurel, Rita Pereira, Christina Guo, Simone Mosole, Daniela Brina, Mariantonietta D’Ambrosio, Emiliano Pasquini, Clarissa Spataro, Elena Zagato, Andrea Rinaldi, Mattia Pedotti, Simona Di Lascio, Francesco Meani, Monica Montopoli, Matteo Ferrari, Andrea Gallina, Luca Varani, Ricardo Pereira Mestre, Marco Bolis, Silke Gillessen Sommer, Johann de Bono, Arianna Calcinotto, and Andrea Alimonti
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Cancer Research ,Oncology ,HDAC inhibitor ,neutrophils ,tumor secretome ,TREM2 ,tumor microenvironment ,markers of senescence ,Senescence ,prostate cancer ,APOE ,immune-senescence - Published
- 2023
32. The SARS-CoV-2 spike protein binds and modulates estrogen receptors
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Oscar Solis, Andrea R. Beccari, Daniela Iaconis, Carmine Talarico, Camilo A. Ruiz-Bedoya, Jerome C. Nwachukwu, Annamaria Cimini, Vanessa Castelli, Riccardo Bertini, Monica Montopoli, Veronica Cocetta, Stefano Borocci, Ingrid G. Prandi, Kelly Flavahan, Melissa Bahr, Anna Napiorkowski, Giovanni Chillemi, Masato Ooka, Xiaoping Yang, Shiliang Zhang, Menghang Xia, Wei Zheng, Jordi Bonaventura, Martin G. Pomper, Jody E. Hooper, Marisela Morales, Avi Z. Rosenberg, Kendall W. Nettles, Sanjay K. Jain, Marcello Allegretti, and Michael Michaelides
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Multidisciplinary ,Receptors, Estrogen ,SARS-CoV-2 ,Cricetinae ,Spike Glycoprotein, Coronavirus ,Fixació de proteïnes ,Estrogen Receptor alpha ,Pandèmia de COVID-19, 2020 ,Protein binding ,Animals ,Humans ,COVID-19 ,COVID-19 Pandemic, 2020 - Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ERα). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ERα binding mode. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ERα lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ERα expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ERα interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS-CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.
- Published
- 2022
33. MP54-11 THE ROLE OF A DNA METHYLATION TEST IN THE SURVEILLANCE OF BLADDER CANCER: A SINGLE-CENTER BLINDED PROSPECTIVE STUDY
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Marialaura Righetto, Daniele Modonutti, Monica Montopoli, Francesco Pagano, Fabrizio Dal Moro, and Mariangela Mancini
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Urology - Published
- 2022
34. Milk kefir enriched with inulin-grafted seed extract from white wine pomace: chemical characterisation, antioxidant profile and in vitro gastrointestinal digestion
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Gabriele Carullo, Umile Gianfranco Spizzirri, Monica Montopoli, Veronica Cocetta, Biagio Armentano, Mattia Tinazzi, Fabio Sciubba, Gianluca Giorgi, Maria Enrica Di Cocco, Torsten Bohn, Francesca Aiello, and Donatella Restuccia
- Subjects
grafting reaction ,Antioxidant activity ,fermented milk ,grape pomace ,biopolymers ,epithelial Caco-2 cells ,gastrointestinal digestion ,symbiotic food ,kefir ,Industrial and Manufacturing Engineering ,bioaccessibility ,Food Science - Published
- 2022
35. Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids- and NF-κB-mediated signaling
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Borgonetti, Vittoria, Cristina, Benatti, Paolo, Governa, Giovanni, Isoldi, Federica, Pellati, Silvia, Alboni, Fabio, Tascedda, Monica, Montopoli, Galeotti, Nicoletta, Fabrizio, Manetti, Elisabetta, Miraldi, Marco, Biagi, and Giovanna, Rigillo
- Subjects
cannabis ,CB2 receptors ,neuroinflammation - Published
- 2022
36. Anti-inflammatory activity of a fixed combination of probiotics and herbal extract in an in-vitro model of intestinal inflammation by stimulating Caco-2 cells with LPS-conditioned THP-1 cells medium
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Veronica Cocetta, Vittoria Borgonetti, Ilaria Carnevali, Monica Montopoli, Paolo Governa, and Marco Biagi
- Subjects
Lipopolysaccharides ,medicine.drug_class ,THP-1 Cells ,Lactobacillus reuteri ,Anti-Inflammatory Agents ,Inflammation ,Pharmacology ,Inflammatory bowel disease ,Anti-inflammatory ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,030225 pediatrics ,medicine ,Humans ,Intestinal Mucosa ,Barrier function ,Lactobacillus acidofilus ,business.industry ,Trans-epithelial electrical resistance (TEER) ,Probiotics ,Interleukin-8 ,medicine.disease ,Inflammatory Bowel Diseases ,Inflammatory bowel diseases ,Caco-2 cells ,THP-1 cells ,Cytokines ,Anti- inflammatory activity ,Interleukin 10 ,030228 respiratory system ,Paracellular transport ,Culture Media, Conditioned ,Pediatrics, Perinatology and Child Health ,medicine.symptom ,Caco-2 Cells ,business - Abstract
Background Inflammatory bowel disease (IBD) is an inflammatory condition of the gastrointestinal tract, characterized by chronic and relapsing immune system activation, often diagnosed in adolescence, with a rising incidence in pediatric populations. IBD results from altered interactions between gut microbes and the intestinal immune system which induce an aberrant immune response, thus anti-inflammatory or immunosuppressive therapies are generally used. Recent interest has been given to the identification of integrative and complementary approaches that could be able to restore and preserve the intestinal barrier function. Methods In this work, we tested the effect of a fixed combination of probiotics and herbal extract (ColikindGocce®, CKG) in an in vitro model of intestinal inflammation. CaCo-2cells stimulated with LPS-conditioned monocytes culture medium was used as a paradigm of intestinal inflammation. The possible effect of CKG in maintaining the homeostasis of the intestinal epithelial barrier was investigated by measurement of the trans- epithelial electrical resistance, the paracellular permeability, and the release of inflammatory cytokines (TNF-α, IL8, and IL10). Results Results obtained in this work demonstrated that CKG is able to prevent the impairment of intestinal barrier function induced by inflammation, ameliorating the transepithelial electrical resistance and the paracellular permeability of the Caco-2 monolayer; moreover, CKG is able to counteract the increased release of TNF-a and IL-8 induced by inflammatory stimulus, thus reducing the intestinal inflammation. Conclusions This work underlines the protective effect of CKG on intestinal barrier, reducing the damages induced by inflammatory stimulus. This suggests CKG as an interesting product in the management of intestinal inflammatory conditions.
- Published
- 2022
37. Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling
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Vittoria, Borgonetti, Cristina, Benatti, Paolo, Governa, Giovanni, Isoldi, Federica, Pellati, Silvia, Alboni, Fabio, Tascedda, Monica, Montopoli, Nicoletta, Galeotti, Fabrizio, Manetti, Elisabetta, Miraldi, Marco, Biagi, and Giovanna, Rigillo
- Subjects
Lipopolysaccharides ,Receptor, Cannabinoid, CB2 ,cannabidiol ,Cannabis sativa L ,inflammation ,microglia ,phytocomplex ,β-Caryophyllene ,NF-kappa B ,Cytokines ,Cannabis ,Endocannabinoids - Abstract
Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD- and terpenes-enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV-2 microglial cells, compared with CBD and β-caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS-induced upregulation of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was significantly attenuated by CSE and only partially by CBD, whereas CAR was ineffective. In BV-2 cells, these anti-inflammatory effects exerted by CSE phytocomplex were only partially dependent on CB2r modulation and they were mediated by the regulation of enzymes responsible for the endocannabinoids metabolism, by the inhibition of reactive oxygen species release and the modulation of JNK/p38 cascade with consequent NF-κB p65 nuclear translocation suppression. Our data suggest that C. sativa phytocomplex and its multitarget mechanism could represent a novel therapeutic strategy for neuroinflammatory-related diseases.
- Published
- 2022
38. Clinical evidence of interaction between nutraceutical supplementation and platinum-based chemotherapy
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Monica Montopoli, Veronica Cocetta, Mattia Tinazzi, Isabella Giacomini, Benedetta Rosato, Eugenio Ragazzi, and Massimiliano Berretta
- Subjects
Pharmacology ,nutraceuticals ,clinical evidence ,chemotherapy ,interaction ,nutraceutical supplementation ,platinum-agents ,toxicity ,Drug Discovery ,Organic Chemistry ,Molecular Medicine ,Biochemistry - Abstract
Abstract: Platinum agents, which include cisplatin, oxaliplatin and carboplatin, are chemotherapeutic drugs that represent the first-line treatment for different types of solid tumors, such as ovarian, head and neck, testicular, and bladder cancers. Their beneficial effect is limited by the onset of drug resistance and severe toxicities, involving mainly ototoxicity, neurotoxicity and nephrotoxicity. Recent studies highlight the supplementation of herbal products, vitamins and minerals with antioxidant properties to prevent and protect from side effects. In particular, the introduction of nutraceuticals associated with chemotherapy has improved the patients’ quality of life. However, if from one side, complementary and alternative medicine ameliorates chemotherapeutics-induced toxicities, from the other side, it is important to take into consideration the possible interference with drug metabolism. This review aims to consider the current literature focusing on clinical trials that report an association between nutraceutical supplementation and platinum- based chemotherapy to prevent toxicities, highlighting both beneficial and side effects.
- Published
- 2022
39. Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy
- Author
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Caterina Vianello, Veronica Cocetta, Daniela Catanzaro, Gerald W Dorn, Angelo De Milito, Flavio Rizzolio, Vincenzo Canzonieri, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli, Vincenzo Quagliariello, Annabella Di Mauro, Simona Losito, Nicola Maurea, Scaffa Cono, Gabriele Sales, Luca Scorrano, Marta Giacomello, Monica Montopoli, Vianello, Caterina, Cocetta, Veronica, Catanzaro, Daniela, Dorn, Gerald W, De Milito, Angelo, Rizzolio, Flavio, Canzonieri, Vincenzo, Cecchin, Erika, Roncato, Rossana, Toffoli, Giuseppe, Quagliariello, Vincenzo, Di Mauro, Annabella, Losito, Simona, Maurea, Nicola, Cono, Scaffa, Sales, Gabriele, Scorrano, Luca, Giacomello, Marta, and Montopoli, Monica
- Subjects
inorganic chemicals ,Cancer Research ,Immunology ,Drug Resistance ,Settore BIO/11 - Biologia Molecolare ,Antineoplastic Agents ,Bone Neoplasms ,Bone Neoplasm ,Carcinoma, Ovarian Epithelial ,Cell Line ,Antineoplastic Agent ,Cellular and Molecular Neuroscience ,Ovarian Epithelial ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Autophagy ,Drug Resistance, Neoplasm ,Female ,Humans ,Membrane Proteins ,Mitochondria ,Cisplatin ,Osteosarcoma ,Ovarian Neoplasms ,Membrane Protein ,neoplasms ,Proto-Oncogene Protein ,Tumor ,Carcinoma ,Cell Biology ,female genital diseases and pregnancy complications ,Neoplasm ,Human - Abstract
Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.
- Published
- 2021
40. Chemotherapy-Induced Hepatotoxicity in HIV Patients
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Vincenzo Quagliarello, Saman Sharifi, Sergio Facchini, Alessandra Pierantoni, Massimiliano Berretta, Silvia Bressan, and Monica Montopoli
- Subjects
medicine.medical_specialty ,drug-drug interactions ,hepatotoxicity ,QH301-705.5 ,medicine.medical_treatment ,Human immunodeficiency virus (HIV) ,Antineoplastic Agents ,HIV Infections ,Review ,medicine.disease_cause ,chemotherapy ,Chemotherapy induced ,Antiretroviral Therapy, Highly Active ,Medicine ,Humans ,Drug Interactions ,Biology (General) ,Intensive care medicine ,Chemotherapy ,business.industry ,Cancer ,HIV ,General Medicine ,Immunotherapy ,medicine.disease ,Discontinuation ,Clinical trial ,Hiv patients ,immunotherapy ,Chemical and Drug Induced Liver Injury ,business ,ART - Abstract
Human immunodeficiency virus (HIV) affects more than 37 million people globally, and in 2020, more than 680,000 people died from HIV-related causes. Recently, these numbers have decrease substantially and continue to reduce thanks to the use of antiretroviral therapy (ART), thus making HIV a chronic disease state for those dependent on lifelong use of ART. However, patients with HIV have an increased risk of developing some type of cancer compared to patients without HIV. Therefore, treatment of patients who are diagnosed with both HIV and cancer represents a complicated scenario because of the risk associated with drug–drug interaction (DDIs) and related toxicity. Selection of an alternative chemotherapy or ART or temporarily discontinuation of ART constitute a strategy to manage the risk of DDIs. Temporarily withholding ART is the less desirable clinical plan but risks and benefits must be considered in each scenario. In this review we focus on the hepatotoxicity associated with a simultaneous treatment with ART and chemotherapeutic drugs and mechanisms behind. Moreover, we also discuss the effect on the liver caused by the association of immunotherapeutic drugs, which have recently been used in clinical trials and also in HIV patients.
- Published
- 2021
41. Novel Adenosine Triphosphate-Based Nutraceutical Formulation to Prevent Non-Steroidal Anti-Inflammatory Drug Enteric Cell Toxicity: Preliminary
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Andrea, Fratter, Damiano, Biagi, Isabella, Giacomini, Monica, Montopoli, and Veronica, Cocetta
- Subjects
Adenosine Triphosphate ,Anti-Inflammatory Agents, Non-Steroidal ,Dietary Supplements ,Intestine, Small ,Humans - Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed and self-prescribed drugs to treat inflammation and pain associated with several conditions. Although their efficacy and overall safety have been recognized when used according to medical prescriptions and for a short period time, their acute impact on enteric physiology has rarely been studied. NSAIDs are known to cause gastrointestinal side effects due to their intrinsic mechanism of action, which involves prostaglandins synthesis, leading to impaired mucopolysaccharide layer production. Despite this well-known and investigated side effect, the short- and long-term influences of acute administration of these drugs on the biochemical environment of enteric cells are not well understood. This study investigates the rate of adenosine triphosphate (ATP) loss and permeability alterations occurring in a model of human enteric cells, as a consequence of acute administration of NSAIDs as major perpetrators of enteric toxicity. For the first time, we investigate the ability of a novel ATP-containing formulation to prevent ATP hydrolysis in the stomach and ensure its delivery at the proximal duodenal site.
- Published
- 2021
42. Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression
- Author
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R Taibi, Monica Montopoli, Simona Buccolo, Andrea Paccone, Ernesta Cavalcanti, Martina Iovine, Gerardo Botti, Vincenzo Quagliariello, Massimiliano Berretta, and Nicola Maurea
- Subjects
0301 basic medicine ,Cancer Research ,Chemokine ,cardio-oncology ,sunitinib ,medicine.disease_cause ,urologic and male genital diseases ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,polydatin ,Medicine ,RC254-282 ,Original Research ,Cardiotoxicity ,biology ,business.industry ,Sunitinib ,chemokine ,microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Inflammasome ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Cancer research ,business ,Tyrosine kinase ,Oxidative stress ,medicine.drug - Abstract
Renal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. Sunitinib, a recently-approved, multi-targeted Tyrosine Kinases Inhibitor (TKi), prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. Polydatin (3,4’,5-trihydroxystilbene-3-β-d-glucoside) is a monocrystalline compound isolated from Polygonum cuspidatum with consolidated anti-oxidant and anti-inflammatory properties, however no studies investigated on its putative cardioprotective and chemosensitizing properties during incubation with sunitinib. We investigated on the effects of polydatin on the oxidative stress, NLRP3 inflammasome and Myd88 expression, highlighting on the production of cytokines and chemokines (IL-1β, IL-6, IL-8, CXCL-12 and TGF-β) during treatment with sunitinib. Exposure of cardiomyocytes and cardiomyoblasts (AC-16 and H9C2 cell lines) and human renal adenocarcinoma cells (769‐P and A498) to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly iROS, MDA and LTB4 compared to only sunitinib-treated cells (Pin vitro, indicate that polydatin, besides reducing oxidative stress, reduces key chemokines involved in cancer cell survival, chemoresistance and cardiac damages of sunitinib through downregulation of NLRP3-MyD88 pathway, applying as a potential nutraceutical agent in preclinical studies of preventive cardio-oncology.
- Published
- 2021
43. ApoE-TREM2 axis induces pathogenic senescent-like myeloid cells in prostate cancer
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Christina Guo, Andrea Alimonti, Emiliano Pasquini, Rydell Arzola, Angela Rita Elia, Clarissa Spataro, Andrea Rinaldi, Monica Montopoli, Arianna Calcinotto, Rita de Cássia Pereira, Bora Gurel, Ricardo Pereira Mestre, Mateus Crespo, Bianca Calì, D'ambrosio Mariantonietta, Nicolò Bancaro, Simone Mosole, Marco Bolis, Giuseppe Attanasio, Simona Di Lascio, Johann S. de Bono, Elena Zagato, Martina Troiani, and Francesco Meani
- Subjects
Apolipoprotein E ,Prostate cancer ,Text mining ,business.industry ,TREM2 ,Myeloid cells ,medicine ,Cancer research ,medicine.disease ,business - Abstract
The authors have requested that this preprint be removed from Research Square.
- Published
- 2021
44. Hereditary Spastic Paraplegia and Future Therapeutic Directions: Beneficial Effects of Small Compounds Acting on Cellular Stress
- Author
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Genny Orso, Chiara Vantaggiato, Monica Montopoli, and Sentiljana Gumeni
- Subjects
N-acetyl cysteine ,Hereditary spastic paraplegia ,naringenin ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Review ,Bioinformatics ,Salubrinal ,guanabenz ,chemistry.chemical_compound ,cell stress ,salubrinal ,medicine ,Spasticity ,hereditary spastic paraplegia ,Zebrafish ,biology ,Mechanism (biology) ,business.industry ,rapamycin ,General Neuroscience ,biology.organism_classification ,medicine.disease ,chemistry ,Progressive spasticity ,methylene blue ,Animal studies ,medicine.symptom ,Guanabenz ,business ,medicine.drug ,Neuroscience ,RC321-571 - Abstract
Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative conditions that share a characteristic feature of degeneration of the longest axons within the corticospinal tract, which leads to progressive spasticity and weakness of the lower limbs. Mutations of over 70 genes produce defects in various biological pathways: axonal transport, lipid metabolism, endoplasmic reticulum (ER) shaping, mitochondrial function, and endosomal trafficking. HSPs suffer from an adequate therapeutic plan. Currently the treatments foreseen for patients affected by this pathology are physiotherapy, to maintain the outgoing tone, and muscle relaxant therapies for spasticity. Very few clinical studies have been conducted, and it’s urgent to implement preclinical animal studies devoted to pharmacological test and screening, to expand the rose of compounds potentially attractive for clinical trials. Small animal models, such asDrosophila melanogasterand zebrafish, have been generated, analyzed, and used as preclinical model for screening of compounds and their effects. In this work, we briefly described the role of HSP-linked proteins in the organization of ER endomembrane system and in the regulation of ER homeostasis and stress as a common pathological mechanism for these HSP forms. We then focused our attention on the pharmacodynamic and pharmacokinetic features of some recently identified molecules with antioxidant property, such as salubrinal, guanabenz, N-acetyl cysteine, methylene blue, rapamycin, and naringenin, and on their potential use in future clinical studies. Expanding the models and the pharmacological screening for HSP disease is necessary to give an opportunity to patients and clinicians to test new molecules.
- Published
- 2021
45. A Fixed Combination of Probiotics and Herbal Extracts Attenuates Intestinal Barrier Dysfunction from Inflammatory Stress in an In vitro Model Using Caco-2 Cells
- Author
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Marco Biagi, Maria Cecilia Giron, Veronica Cocetta, Daniela Catanzaro, Vittoria Borgonetti, Eugenio Ragazzi, Monica Montopoli, Paolo Governa, and Ilaria Carnevali
- Subjects
0301 basic medicine ,IBD ,Lactobacillus reuteri ,Inflammation ,adherence junctions proteins ,Pharmacology ,Occludin ,03 medical and health sciences ,0302 clinical medicine ,Lactobacillus acidophilus ,Stress, Physiological ,IBD, Caco-2 cells, Lactobacillus reuteri, Lactobacillus acidophilus, Trans Epithelial Electrical Resistance (TEER) ,medicine ,Humans ,Caco-2 cells ,Barrier function ,biology ,Tight junction ,Plant Extracts ,business.industry ,Probiotics ,General Medicine ,biology.organism_classification ,030104 developmental biology ,Caco-2 ,030220 oncology & carcinogenesis ,Paracellular transport ,Trans Epithelial Electrical Resistance (TEER) ,medicine.symptom ,business - Abstract
Background: Inflammatory Bowel Diseases (IBD), are considered a growing global disease, with about ten million people being affected worldwide. Maintenance of intestinal barrier integrity is crucial for preventing IBD onset and exacerbations. Some recent patents regarding oily formulations containing probiotics (WO2010122107A1 and WO2010103374A9) and the use of probiotics for gastrointestinal complaints (US20110110905A1 and US9057112B2) exist, or are pending application. Objective: In this work, we studied the effect of a fixed combination of registered Lactobacillus reuteri and Lactobacillus acidophilus strains and herbal extracts in an in vitro inflammation experimental model. Methods: Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin Tight Junctions (TJs) were also investigated by mean of immunofluorescence. Results: Pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. Conclusions: In summary, the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBD conditions.
- Published
- 2019
46. Identification of novel therapeutic approaches to selectively target senescent cells in prostate cancer
- Author
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SILVIA BRESSAN, Brina, Daniela, Sara Zumerle, MONICA MONTOPOLI, and Andrea Alimonti
- Published
- 2021
47. Further assessment of Salvia haenkei as an innovative strategy to counteract skin photo-aging and restore the barrier integrity
- Author
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Eugenio Ragazzi, Stefano Dall'Acqua, Stefania Sut, Miriam Saponaro, Veronica Cocetta, Giorgia Miolo, Isabella Giacomini, Monica Montopoli, Jessica Cadau, Genny Orso, Luca Menilli, Daniela Catanzaro, and Andrea Pagetta
- Subjects
chemistry.chemical_classification ,Premature aging ,Aging ,Reactive oxygen species ,integumentary system ,Endogenous Factors ,Tight junction ,skin barrier integrity ,Chemistry ,Salvia haenkei ,wound healing ,Cell Biology ,Skin Aging ,Cell biology ,skin aging ,skin photoaging ,HaCaT ,Cell culture ,Wound healing - Abstract
Skin is the essential barrier of the human body which performs multiple functions. Endogenous factors, in concert with external assaults, continuously affect skin integrity, leading to distinct structural changes that influence not only the skin appearance but also its various physiological functions. Alterations of the barrier functions lead to an increased risk of developing disease and side reactions, thus the importance of maintaining the integrity of the epidermal barrier and slowing down the skin aging process is evident. Salvia haenkei (SH) has been recently identified as a potential anti-senescence agent; its extract is able to decrease the level of senescent cells by affecting the IL1α release and reducing reactive oxygen species (ROS) generation. In this study, SH extract was tested on human keratinocyte cell line (HaCaT) exposed to stress factors related to premature aging of cells such as free radicals and ultraviolet B radiation. We confirmed that SH acts as scavenger of ROS and found its ability to restore the skin barrier integrity by reinforcing the cytoskeleton structure, sealing the tight junctions and increasing the migration rate of cells. Given these results, this work becomes relevant, identifying Salvia haenkei as a compound useful for anti-aging skin treatment in clinical performance.
- Published
- 2021
48. Clinical outcome of SARS-CoV-2 infection in breast and ovarian cancer patients underwent anti-estrogenic therapy
- Author
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Veronica Cocetta, Monica Montopoli, Stefano Guzzinati, Manuel Zorzi, Massimo Rugge, A. Calcinotto, Emanuela Bovo, and Tommaso Prayer-Galetti
- Subjects
Oncology ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,Breast Neoplasms ,Carcinoma, Ovarian Epithelial ,Internal medicine ,Ovarian Epithelial ,Medicine ,Humans ,Letter to the Editor ,Ovarian Neoplasms ,business.industry ,SARS-CoV-2 ,Carcinoma ,COVID-19 ,Estrogens ,Hematology ,medicine.disease ,Female ,business ,Ovarian cancer - Published
- 2021
49. Polydatin reduces cardiotoxicity of tyrosine kinase inhibitor sunitinib by decreasing pro-oxidative stress, pro-inflammatory cytokines and NLRP3 inflammasome expression
- Author
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R Taibi, Martina Iovine, Gerardo Botti, Simona Buccolo, Massimiliano Berretta, Michelino De Laurentiis, Ernesta Cavalcanti, Vincenzo Quagliariello, Nicola Maurea, Monica Montopoli, and Raffaele Di Francia
- Subjects
Cancer Research ,Cardiotoxicity ,medicine.drug_class ,business.industry ,Sunitinib ,Inflammasome ,medicine.disease_cause ,Tyrosine-kinase inhibitor ,Proinflammatory cytokine ,Oncology ,medicine ,Cancer research ,business ,Oxidative stress ,medicine.drug - Abstract
e15065 Background: : Polydatin has anticancer and anti-inflammatory properties, however no studies investigated on its putative cardioprotective effects against anticancer therapies. Sunitinib, a recently-approved, multi-targeted tyrosine kinases inhibitor, prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. We investigated on the reduction of cytokines and growth factors of polydatin resulting in putative cardioprotective effects. Methods: Human fetal cardiomyocytes were untreated (control) or treated for 48 h with polydatin (50,100,200 and 400 µM) or sunitinib (5,10,25 and 50 µM) alone or combined to polydatin. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Exposure of adult cardiomyocytes to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly intracellular reactive oxygen species, lipid peroxidation and cytochrome c release from mitochondria leading to a reduction in cell death compared to cells exposed to sunitinib alone. Polydatin reduces expression of pro-inflammatory cytokines and growth factors involved in myocardial damages and down-regulates the signaling pathway of NLRP3 inflammasome and NF-κB, increasing cellular resistance to sunitinib-mediated damages. Conclusions: Data of the present study, although in vitro, indicate that polydatin, besides reducing oxidative stress, has cardioprotective and anti-inflammatory properties, thus indicating one the mechanism(s) by which this metabolite of resveratrol might decrease sunitinib-mediated cardiotoxicity.
- Published
- 2021
50. The Bladder EpiCheck Test as a Non-Invasive Tool Based on the Identification of DNA Methylation in Bladder Cancer Cells in the Urine: A Review of Published Evidence
- Author
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Filiberto Zattoni, Marialaura Righetto, Mariangela Mancini, Sara Zumerle, and Monica Montopoli
- Subjects
Urinary Bladder ,030232 urology & nephrology ,Context (language use) ,Review ,Catalysis ,Epigenesis, Genetic ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Biomarkers ,Bladder cancer ,DNA methylation ,Biomarkers, Tumor ,Medicine ,Humans ,Epigenetics ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,business.industry ,Organic Chemistry ,Cancer ,biomarkers ,General Medicine ,Methylation ,medicine.disease ,Prognosis ,Computer Science Applications ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Cancer research ,Biomarker (medicine) ,bladder cancer ,business ,DNA - Abstract
Recently, there has been a great effort to develop tests based on non-invasive urinary biomarkers (NMIBCs). These tests are based on the fact that NMIBCs are heterogeneous at the molecular level and can be divided into different molecular groups useful to predict prognosis and response to treatment. The assessment of epigenetic alterations, such as DNA methylation, represents a promising cancer biomarker. DNA methylation is an epigenetic modification that affects gene expression without modifying the DNA sequence. Several studies have highlighted the presence of methylated loci in the context of bladder cancer, indicating its potential application as a diagnostic and prognostic biomarker. One of the novel assays based on a DNA methylation profile, the Bladder EpiCheck, analyzes DNA from spontaneous urine, detecting disease-specific DNA methylation patterns in bladder cancer patients. This test, due to its non-invasive nature and highly promising performance could, in future, become an invaluable tool in the follow-up of bladder cancer patients. Potential new applications could include diagnosis and surveillance of upper-tract disease, for the replacement of invasive testing and ureteroscopy.
- Published
- 2020
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