181 results on '"Fiorenza, Orlando"'
Search Results
2. ER-mitochondria association negatively affects wound healing by regulating NLRP3 activation
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Caterina Licini, Gianluca Morroni, Guendalina Lucarini, Veronica Angela Maria Vitto, Fiorenza Orlando, Sonia Missiroli, Gloria D’Achille, Mariasole Perrone, Tatiana Spadoni, Laura Graciotti, Giorgia Bigossi, Mauro Provinciali, Annamaria Offidani, Monica Mattioli-Belmonte, Oscar Cirioni, Paolo Pinton, Oriana Simonetti, and Saverio Marchi
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Cytology ,QH573-671 - Abstract
Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent of acute bacterial skin and skin-structure infections (ABSSSI), one of the major challenges to the health system worldwide. Although the use of antibiotics as the first line of intervention for MRSA-infected wounds is recommended, important side effects could occur, including cytotoxicity or immune dysregulation, thus affecting the repair process. Here, we show that the oxazolidinone antibiotic linezolid (LZD) impairs wound healing by aberrantly increasing interleukin 1 β (IL-1β) production in keratinocytes. Mechanistically, LZD triggers a reactive oxygen species (ROS)-independent mitochondrial damage that culminates in increased tethering between the endoplasmic reticulum (ER) and mitochondria, which in turn activates the NLR family pyrin domain-containing 3 (NLRP3) inflammasome complex by promoting its assembly to the mitochondrial surface. Downregulation of ER-mitochondria contact formation is sufficient to inhibit the LZD-driven NLRP3 inflammasome activation and IL-1β production, restoring wound closure. These results identify the ER-mitochondria association as a key factor for NLRP3 activation and reveal a new mechanism in the regulation of the wound healing process that might be clinically relevant.
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- 2024
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3. Transfer of the longevity-associated variant of BPIFB4 gene rejuvenates immune system and vasculature by a reduction of CD38+ macrophages and NAD+ decline
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Elena Ciaglia, Valentina Lopardo, Francesco Montella, Albino Carrizzo, Paola Di Pietro, Marco Malavolta, Robertina Giacconi, Fiorenza Orlando, Monica Cattaneo, Paolo Madeddu, Carmine Vecchione, and Annibale Alessandro Puca
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Cytology ,QH573-671 - Abstract
Abstract As we age, our body experiences chronic, systemic inflammation contributing to the morbidity and mortality of the elderly. The senescent immune system has been described to have a causal role in driving systemic aging and therefore may represent a key therapeutic target to prevent pathological consequences associated with aging and extend a healthy lifespan. Previous studies from our group associated a polymorphic haplotype variant in the BPIFB4 gene (LAV-BPIFB4) with exceptional longevity. Transfer of the LAV-BPIFB4 in preclinical models halted the progression of cardiovascular diseases (CVDs) and frailty by counterbalancing chronic inflammation. In the present study, we aimed to delineate the action of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer (AAV-LAV-BPIFB4) on the deleterious age-related changes of the immune system and thereby the senescence-associated events occurring in C57BL/6J mice aged 26 months. Our in vivo data showed that 26-months-old mice had a higher frequency of CD45+SA-beta Gal+ immune cells in peripheral blood than young (4-months-old) C57BL/6J mice. Notably, AAV-LAV-BPIFB4 gene transfer in aged mice reduced the pool of peripheral immunosenescent cells that were shown to be enriched in the spleen. In addition, the proper tuning of the immune secretory phenotype (IL1βlow, IL6low, IL10high) associated with a significant reduction in SA-beta Gal-positive area of aorta from AAV-LAV treated mice. At the functional level, the reduction of senescence-associated inflammation ensured sustained NAD+ levels in the plasma of AAV-LAV-BPIFB4 old mice by preventing the NADase CD38 increase in F4/80+ tissue-resident macrophages and Ly6Chigh pro-inflammatory monocytes of the spleen and bone marrow. Finally, to validate the clinical implication of our findings, we showed that Long-living-individuals (LLIs, >95 years), which delay CVDs onset, especially if LAV-carriers, were characterized by high NAD+ levels. In conclusion, the new senotherapeutic action of LAV-BPIFB4 may offer a valuable therapeutic tool to control aging and reduce the burden of its pathophysiological disorders, such as CVDs.
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- 2022
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4. Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice
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Maria Elisa Giuliani, Veronica Barbi, Giorgia Bigossi, Serena Marcozzi, Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Fiorenza Orlando, Elena Ciaglia, Monica Cattaneo, Alessia Mongelli, Carlo Gaetano, Mauro Provinciali, Annibale Alessandro Puca, and Marco Malavolta
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aging ,epigenetic clock ,frailty ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging. In this study, we show that the systemic gene transfer of LAV-BPIFB4 in aged C57BL/6J mice was associated with a significant reduction in the epigenetic clock-based biological age, as measured by a three CpG clock method. Furthermore, LAV-BPIFB4 gene transfer resulted in an improvement of the Vitality Score with a reduction in the Frailty Index. These findings further support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in aged mice, with potential implications for future therapies to prevent frailty in humans.
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- 2023
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5. Effects of Normoxia, Hyperoxia, and Mild Hypoxia on Macro-Hemodynamics and the Skeletal Muscle Microcirculation in Anesthetised Rats
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Elisa Damiani, Erika Casarotta, Fiorenza Orlando, Andrea Carsetti, Claudia Scorcella, Roberta Domizi, Erica Adrario, Silvia Ciucani, Mauro Provinciali, and Abele Donati
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hyperoxia ,hypoxia ,microcirculation ,oxygen ,hemodymamics ,Medicine (General) ,R5-920 - Abstract
Objectives: Excessive oxygen (O2) administration may have a negative impact on tissue perfusion by inducing vasoconstriction and oxidative stress. We aimed to evaluate the effects of different inhaled oxygen fractions (FiO2) on macro-hemodynamics and microvascular perfusion in a rat model.Methods: Isoflurane-anesthetised spontaneously breathing male Wistar rats were equipped with arterial (carotid artery) and venous (jugular vein) catheters and tracheotomy, and randomized into three groups: normoxia (FiO2 21%, n = 6), hyperoxia (FiO2 100%, n = 6) and mild hypoxia (FiO2 15%, n = 6). Euvolemia was maintained by infusing Lactate Ringer solution at 10 ml/kg/h. At hourly intervals for 4 h we collected measurements of: mean arterial pressure (MAP); stroke volume index (SVI), heart rate (HR), respiratory rate (by means of echocardiography); arterial and venous blood gases; microvascular density, and flow quality (by means of sidestream dark field videomicroscopy on the hindlimb skeletal muscle).Results: MAP and systemic vascular resistance index increased with hyperoxia and decreased with mild hypoxia (p < 0.001 in both cases, two-way analysis of variance). Hyperoxia induced a reduction in SVI, while this was increased in mild hypoxia (p = 0.002). The HR increased under hyperoxia (p < 0.05 vs. normoxia at 3 h). Cardiax index, as well as systemic O2 delivery, did not significantly vary in the three groups (p = 0.546 and p = 0.691, respectively). At 4 h, microvascular vessel surface (i.e., the percentage of tissue surface occupied by vessels) decreased by 29 ± 4% in the hyperoxia group and increased by 19 ± 7 % in mild hypoxia group (p < 0.001). Total vessel density and perfused vessel density showed similar tendencies (p = 0.003 and p = 0.005, respectively). Parameters of flow quality (microvascular flow index, percentage of perfused vessels, and flow heterogeneity index) remained stable and similar in the three groups.Conclusions: Hyperoxia induces vasoconstriction and reduction in skeletal muscle microvascular density, while mild hypoxia has an opposite effect.
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- 2021
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6. Targeting Multiple Mitochondrial Processes by a Metabolic Modulator Prevents Sarcopenia and Cognitive Decline in SAMP8 Mice
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Dario Brunetti, Emanuela Bottani, Agnese Segala, Silvia Marchet, Fabio Rossi, Fiorenza Orlando, Marco Malavolta, Michele O. Carruba, Costanza Lamperti, Mauro Provinciali, Enzo Nisoli, and Alessandra Valerio
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essential amino acids ,aging ,sarcopenia ,cognitive impairment ,tricarboxylic acid cycle ,mitochondrial respiratory chain ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The age-dependent declines of skeletal muscle and cognitive functions often coexist in elderly subjects. The underlying pathophysiological mechanisms share common features of mitochondrial dysfunction, which plays a central role in the development of overt sarcopenia and/or dementia. Dietary supplementation with formulations of essential and branched-chain amino acids (EAA-BCAA) is a promising preventive strategy because it can preserve mitochondrial biogenesis and function. The senescence-accelerated mouse prone 8 (SAMP8) is considered an accurate model of age-related muscular and cognitive alterations. Hence, we aimed to investigate the progression of mitochondrial dysfunctions during muscular and cognitive aging of SAMP8 mice and to study the effects of a novel EAA-BCAA-based metabolic modulator on these changes. We evaluated body condition, motor endurance, and working memory of SAMP8 mice at 5, 9, 12, and 15 months of age. Parallel changes in protein levels of mitochondrial respiratory chain subunits, regulators of mitochondrial biogenesis and dynamics, and the antioxidant response, as well as respiratory complex activities, were measured in the quadriceps femoris and the hippocampus. The same variables were assessed in 12-month-old SAMP8 mice that had received dietary supplementation with the novel EAA-BCAA formulation, containing tricarboxylic acid cycle intermediates and co-factors (PD-0E7, 1.5 mg/kg/body weight/day in drinking water) for 3 months. Contrary to untreated mice, which had a significant molecular and phenotypic impairment, PD-0E7-treated mice showed preserved healthy body condition, muscle weight to body weight ratio, motor endurance, and working memory at 12 months of age. The PD-0E7 mixture increased the protein levels and the enzymatic activities of mitochondrial complex I, II, and IV and the expression of proliferator-activated receptor γ coactivator-1α, optic atrophy protein 1, and nuclear factor, erythroid 2 like 2 in muscles and hippocampi. The mitochondrial amyloid-β-degrading pitrilysin metallopeptidase 1 was upregulated, while amyloid precursor protein was reduced in the hippocampi of PD-0E7 treated mice. In conclusion, we show that a dietary supplement tailored to boost mitochondrial respiration preserves skeletal muscle and hippocampal mitochondrial quality control and health. When administered at the early onset of age-related physical and cognitive decline, this novel metabolic inducer counteracts the deleterious effects of precocious aging in both domains.
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- 2020
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7. A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis
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Andrea Marchesini, Francesco De Francesco, Monica Mattioli-Belmonte, Nicola Zingaretti, Valentina Riccio, Fiorenza Orlando, Barbara Zavan, and Michele Riccio
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pathological fibrosis ,wound model ,animal model ,scar ,talc ,Biology (General) ,QH301-705.5 - Abstract
Fibrosis is a condition that affects the connective tissue in an organ or tissue in the restorative or responsive phase as a result of injury. The consequences of excessive fibrotic tissue growth may lead to various physiological complications of deformity and impairment due to hypertrophic scars, keloids, and tendon adhesion without understating the psychological impact on the patient. However, no method accurately quantifies the rate and pattern of subcutaneous induced hypertrophic fibrosis. We, therefore, devised a rodent excisional model to evaluate the extent of fibrosis with talc. Tissue specimens were set on formalin, and paraffin sections for histological, immunohistochemical, and molecular analysis talc was used to induce the fibroproliferative mechanism typical of hypertrophic scars. This pathway is relevant to the activation of inflammatory and fibrotic agents to stimulate human hypertrophic scarring. This model reproduces morpho-functional features of human hypertrophic scars to investigate scar formation and assess potential anti-scarring therapies.
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- 2020
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8. Erratum: Correction of Affiliation
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Roberto Ghiselli, Guendalina Lucarini, Monica Ortenzi, Eleonora Salvolini, Stefania Saccomanno, Fiorenza Orlando, Mauro Provinciali, Fabio Casciani, and Mario Guerrieri
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Non-steroidal inflammatory drugs ,inflammation ,colo-colic anastomosis ,peritonitis ,wound healing ,MMP9 ,Biology (General) ,QH301-705.5 - Abstract
This corrects the article "Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration " in volume 64(1):3085 In the published article “Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration” Eur J Histochem 2020;64(1):3085, https://doi.org/10.4081/ejh.2020.3085,” one affiliation was published incorrectly. The authors apologize for any inconvenience that it may have caused. Roberto Ghiselli,1 Guendalina Lucarini,2 Monica Ortenzi,1 Eleonora Salvolini,3 Stefania Saccomanno,2 Fiorenza Orlando,4 Mauro Provinciali,4 Fabio Casciani,1 Mario Guerrieri1 1Clinic of Surgery, Marche Polytechnic University, Ancona 2Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona 3Department of Odontostomatologic and Specialized Clinical Sciences, Marche Polytechnic University, Ancona 4Experimental Animal Models for Aging Units, Research Department, Italian National Institute on Aging (INRCA) IRCCS, Ancona, Italy The affiliation should be corrected as follows: 4Experimental Animal Models for Aging Units, Scientific Technological Area, IRCCS INRCA, Ancona, Italy
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- 2020
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9. Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration
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Roberto Ghiselli, Guendalina Lucarini, Monica Ortenzi, Eleonora Salvolini, Stefania Saccomanno, Fiorenza Orlando, Mauro Provinciali, Fabio Casciani, and Mario Guerrieri
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Non-steroidal inflammatory drugs ,inflammation ,colo-colic anastomosis ,peritonitis ,wound healing ,MMP9 ,Biology (General) ,QH301-705.5 - Abstract
The tissue inflammatory response can influence the outcome of anastomotic healing. Anastomotic leakage represents a dreadful complication after gastrointestinal surgery, in particular sepsis and intra-abdominal infections impair the restorative process of colic anastomoses. It has been debated whether the administration of non-steroidal anti-inflammatory drugs (NSAIDs) is a risk factor for dehiscence, since many patients receive NSAIDs in the early postoperative period. Our aim was, for the first time, to analyze the morpho-functional effects of postoperative administration of two commonly used NSAIDs, Diclofenac and Ketorolac, on the healing process of colo-colic anastomoses constructed under condition of fecal peritonitis in a rat model. Sixty adult male rats underwent two surgical procedures: peritonitis induction and colo-colic anastomosis, and were divided into three groups: 20 rats received saline; 20 rats 4 mg/kg Diclofenac and 20 rats 5 mg/kg Ketorolac. We assessed anastomosis strength, morphological features of tissue wound healing, immunohistochemical metalloproteinase 9 (MMP9) expression and collagen deposition and content by Sirius red staining and hydroxyproline level. We found no significant difference in bursting pressure, collagen content and organization and morphological features between the groups, except a significantly reduced presence of inflammatory cells and MMP9 expression in the groups treated with NSAIDs. Our findings showed that Diclofenac and Ketorolac administration did not affect post-surgical healing and did not increase the leakage risk of colo-colic anastomoses during peritonitis.
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- 2020
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10. Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model
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Oriana Simonetti, Oscar Cirioni, Gaia Goteri, Guendalina Lucarini, Elżbieta Kamysz, Wojciech Kamysz, Fiorenza Orlando, Giulio Rizzetto, Elisa Molinelli, Gianluca Morroni, Roberto Ghiselli, Mauro Provinciali, Andrea Giacometti, and Annamaria Offidani
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animal models ,cathelicidin ,LL-37 ,VEGF ,wound ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: LL-37 is the only human antimicrobial peptide that belongs to the cathelicidins. The aim of the study was to evaluate the efficacy of LL-37 in the management of MRSA-infected surgical wounds in mice. Methods: A wound on the back of adult male BALB/c mice was made and inoculated with Staphylococcus aureus. Two control groups were formed (uninfected and not treated, C0; infected and not treated, C1) and six contaminated groups were treated, respectively, with: teicoplanin, LL-37, given topically and /or systemically. Histological examination of VEGF expression and micro-vessel density, and bacterial cultures of wound tissues, were performed. Results: Histological examination of wounds in the group treated with topical and intraperitoneal LL-37 showed increased re-epithelialization, formation of the granulation tissue, collagen organization, and angiogenesis. Conclusions: Based on the mode of action, LL-37 has a potential future role in the management of infected wounds.
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- 2021
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11. Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
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Mauro Provinciali, Alessandra Barucca, Fiorenza Orlando, and Elisa Pierpaoli
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Medicine ,Science - Abstract
Abstract Cancer vaccines are less effective at old than at young age because of immunosenescence. Besides, in preliminary observations we showed that the immunization with HER-2/neu DNA plasmid in transgenic young mice (standard immunization, SI) delays but not abrogate spontaneous mammary tumours progressively appearing during aging. In this study we evaluated whether booster immunizations (BI) of HER-2/neu transgenic mice with HER-2/neu DNA plasmids every 6 (ECD6), 3 (ECD3), or 1.5 (ECD1.5) months after SI induce a protective immunity that could be maintained over life span. The long term BI significantly improved the effect of SI increasing the number of tumour free mice at 110 weeks of age from 13% (SI) to 58% (BI). Both the number and the volume of tumour masses were reduced in BI than in SI groups. The protective effect of BI was associated with increased antibody production with isotype switching to IgG2a, augmented CD4 T cells, and increased in vivo cytotoxicity of HER-2/neu specific cytotoxic T lymphocytes, mainly in ECD1.5 and ECD3 groups. The transfer of sera from ECD1.5 mice to untreated HER-2/neu mice highly protected against tumour development than sera from SI mice. We conclude that BI induce a protective immunity effective over life span.
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- 2017
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12. Antimetastatic and Antitumor Activities of Orally Administered NAX014 Compound in a Murine Model of HER2-Positive Breast Cancer
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Elisa Pierpaoli, Francesco Piacenza, Gaetano Fiorillo, Paolo Lombardi, Fiorenza Orlando, Carmela Salvatore, Cristina Geroni, and Mauro Provinciali
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berberine ,NAX014 ,breast cancer ,HER-2 ,lung metastases ,senescence ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The natural isoquinoline alkaloid Berberine (BBR) has been shown to possess several therapeutic effects, including anticancer activity. Different BBR derivatives have been designed and synthesized in order to obtain new compounds with enhanced anticancer efficacy. We previously showed that intraperitoneal (IP) administration of the BBR-derived NAX014 compound was able to counteract HER-2 overexpressing mammary tumors onset and progression in transgenic mice. However, the IP administration was found to induce organ toxicity at doses higher than 2.5 mg/Kg. In this study, we evaluated the effect of intragastric (IG) administration of 20 mg/kg of NAX014 on both safety and anticancer efficacy in HER-2/neu transgenic mice. Furthermore, cancer cell dissemination and migration, tumor cell senescence and immunological changes were examined. Our results demonstrated that IG NAX014 administration delayed the onset of mammary tumors with no negative effects on health and survival. NAX014 reduced HER-2 overexpressing BC cells migration in vitro and the frequency of lung metastasis in HER-2/neu transgenic mice. A statistically significant increase of senescence-associated p16 expression was observed in tumors from NAX014-treated mice, and the induction of cell senescence was observed in HER-2 overexpressing BC cells after in vitro treatment with NAX014. Although NAX014 did not modulate the presence of tumor-infiltrating lymphocytes, the level of circulating TNF-α and VEGF was found to be reduced in NAX014-treated mice. The overall results address the NAX014 compound as potential tool for therapeutic strategies against HER-2 overexpressing breast cancer.
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- 2021
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13. Comprehensive longitudinal non-invasive quantification of healthspan and frailty in a large cohort (n = 546) of geriatric C57BL/6 J mice
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Serena Marcozzi, Giorgia Bigossi, Maria Elisa Giuliani, Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Fiorenza Orlando, Agnese Segala, Alessandra Valerio, Enzo Nisoli, Dario Brunetti, Annibale Puca, Federico Boschi, Carlo Gaetano, Alessia Mongelli, Fabrizia Lattanzio, Mauro Provinciali, and Marco Malavolta
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Aging ,Biomarkers of aging ,Epigenetic clock ,Biogerontology ,Geriatrics and Gerontology ,Cellular senescence ,Physical performance - Published
- 2023
14. Determination of Antimetastatic and Antitumor Activities of Orally Administered NAX014 Compound in a Murine Model of HER2-Positive Breast Cancer
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Elisa Pierpaoli, Francesco Piacenza, Gaetano Fiorillo, Paolo Lombardi, Fiorenza Orlando, Carmela Salvatore, Cristina Geroni, and Mauro Provinciali
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- 2022
15. Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice.
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Gianluca Moroncini, Chiara Paolini, Fiorenza Orlando, Chiara Capelli, Antonella Grieco, Cecilia Tonnini, Silvia Agarbati, Eleonora Mondini, Stefania Saccomanno, Gaia Goteri, Silvia Svegliati Baroni, Mauro Provinciali, Martino Introna, Nicoletta Del Papa, and Armando Gabrielli
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Medicine ,Science - Abstract
Lung fibrosis is a severe condition resulting from several interstial lung diseases (ILD) with different etiologies. Current therapy of ILD, especially those associated with connective tissue diseases, is rather limited and new anti-fibrotic strategies are needed. In this study, we investigated the anti-fibrotic activity in vivo of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC). Adult immunocompetent C57BL/6 mice (n. = 8 for each experimental condition) were injected intravenously with hUC-MSC (n. = 2.5 × 105) twice, 24 hours and 7 days after endotracheal injection of bleomycin. Upon sacrifice at days 8, 14, 21, collagen content, inflammatory cytokine profile, and hUC-MSC presence in explanted lung tissue were analyzed. Systemic administration of a double dose of hUC-MSC significantly reduced bleomycin-induced lung injury (inflammation and fibrosis) in mice through a selective inhibition of the IL6-IL10-TGFβ axis involving lung M2 macrophages. Only few hUC-MSC were detected from explanted lungs, suggesting a "hit and run" mechanism of action of this cellular therapy. Our data indicate that hUC-MSC possess strong in vivo anti-fibrotic activity in a mouse model resembling an immunocompetent human subject affected by inflammatory ILD, providing proof of concept for ad-hoc clinical trials.
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- 2018
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16. Identification and Characterization of Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma Cell Lines
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Valentina Pozzi, Davide Sartini, Romina Rocchetti, Andrea Santarelli, Corrado Rubini, Stefano Morganti, Rachela Giuliante, Stefania Calabrese, Giulia Di Ruscio, Fiorenza Orlando, Mauro Provinciali, Franca Saccucci, Lorenzo Lo Muzio, and Monica Emanuelli
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Nicotinamide N-Methyltransferase ,Cancer stem cells ,Head and neck squamous cell carcinoma ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Background/Aims: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. Methods: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. Results: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Conclusion: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy.
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- 2015
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17. Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression
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Oriana, Simonetti, Guendalina, Lucarini, Oscar, Cirioni, Antonio, Zizzi, Fiorenza, Orlando, Mauro, Provinciali, Roberto, Di Primio, Andrea, Giacometti, and Annamaria, Offidani
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- 2013
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18. The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcal Infection
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Andrea Giacometti, Annamaria Offidani, Erika Fornasari, Marco Vivarelli, Pamela Castelli, Mauro Provinciali, Fiorenza Orlando, Leonardo Baldassarre, Carmela Silvestri, Ivana Cacciatore, Oriana Simonetti, Oscar Cirioni, and Federico Mocchegiani
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lipopeptides ,tigecycline ,FS8 ,vascular graft infection ,bacterial biofilm ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.
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- 2013
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19. Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats.
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Elisa Damiani, Can Ince, Fiorenza Orlando, Elisa Pierpaoli, Oscar Cirioni, Andrea Giacometti, Federico Mocchegiani, Paolo Pelaia, Mauro Provinciali, and Abele Donati
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Medicine ,Science - Abstract
BACKGROUND:Sepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis. METHODS:Adult male Wistar rats were equipped with arterial and venous catheters and received an intravenous infusion of lipopolysaccharide (LPS, serotype O127:B8, 10 mg/kg over 30 minutes) or vehicle (SHAM, n = 6). Two hours later, endotoxemic animals were randomized to receive 10 mL/kg of either 4% HSA (LPS+4%HSA, n = 6), 20% HSA (LPS+20%HSA, n = 6) or 0.9% NaCl (LPS+0.9%NaCl, n = 6). No fluids were given to an additional 6 animals (LPS). Vessel density and perfusion were assessed in the skeletal muscle microcirculation with sidestream dark field videomicroscopy at baseline (t0), 2 hours after LPS injection (t1), after HSA infusion (t2) and 1 hour later (t3). The mean arterial pressure (MAP) and heart rate were recorded. Serum endothelin-1 was measured at t2. RESULTS:MAP was stable over time in all groups. The microcirculatory parameters were significantly altered in endotoxemic animals at t1. The infusion of both 4% and 20% HSA similarly increased the perfused vessel density and blood flow velocity and decreased the flow heterogeneity to control values. Microvascular perfusion was preserved in the LPS+20%HSA group at t3, whereas alterations reappeared in the LPS+4%HSA group. CONCLUSIONS:In a rat model of normotensive endotoxemia, the infusion of 4% or 20% HSA produced a similar acute improvement in the microvascular perfusion in otherwise unresuscitated animals.
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- 2016
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20. Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound.
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Oriana Simonetti, Oscar Cirioni, Ivana Cacciatore, Leonardo Baldassarre, Fiorenza Orlando, Elisa Pierpaoli, Guendalina Lucarini, Elena Orsetti, Mauro Provinciali, Erika Fornasari, Antonio Di Stefano, Andrea Giacometti, and Annamaria Offidani
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Medicine ,Science - Abstract
In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x107 CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models.
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- 2016
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21. Potential application of berberine in the treatment of Escherichia coli sepsis
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Paolo Lombardi, Mauro Provinciali, Oriana Simonetti, Andrea Giacometti, Fiorenza Orlando, Elisa Pierpaoli, and Oscar Cirioni
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medicine.drug_class ,medicine.medical_treatment ,Antibiotics ,Population ,Plant Science ,Pharmacology ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,Sepsis ,chemistry.chemical_compound ,Berberine ,In vivo ,Intensive care ,Medicine ,education ,Cause of death ,education.field_of_study ,010405 organic chemistry ,business.industry ,Organic Chemistry ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,business ,Adjuvant - Abstract
Gram-negative sepsis ranks as the leading cause of death in intensive care units. Despite the development of new antibiotics, mortality from gram-negative sepsis remains high. The present study aims to investigate the in vivo effects of berberine (BBR) administration on septic death induced by intraperitoneal Escherichia coli injection. The results showed that (i) single 5 mg/kg dose of BBR increases the survival of septic mice, (ii) BBR administration improves the antimicrobial efficacy of antibiotic drug, (iii) BBR pre-treatment prevents improvements of BBR therapy without affecting the pro-survival effects of antibiotic drug. The effects of BBR administration were associated with immunological alterations represented by changes in CD4+ and CD8+ lymphocytes population and IL-6 and TNF-α production. This study highlighted the benefits of berberine administration as antibiotic adjuvant in E. coli sepsis. Furthermore, information about berberine-induced immunological perturbations and their influence on host response to infection and therapy has been shown.
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- 2020
22. HER2-Displaying M13 Bacteriophages induce Therapeutic Immunity against Breast Cancer
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Junbiao Wang, Alessia Lamolinara, Laura Conti, Mara Giangrossi, Lishan Cui, Maria Beatrice Morelli, Consuelo Amantini, Maurizio Falconi, Caterina Bartolacci, Cristina Andreani, Fiorenza Orlando, Mauro Provinciali, Francesco Domenico Del Pizzo, Francesca Russo, Barbara Belletti, Federica Riccardo, Elisabetta Bolli, Elena Quaglino, Federica Cavallo, Augusto Amici, Manuela Iezzi, and Cristina Marchini
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Cancer Research ,bacteriophages ,breast cancer ,Oncology ,HER2 ,anti-tumor immunity ,Δ16HER2 ,cancer vaccines - Abstract
The advent of trastuzumab has significantly improved the prognosis of HER2-positive (HER2+) breast cancer patients; nevertheless, drug resistance limits its clinical benefit. Anti-HER2 active immunotherapy represents an attractive alternative strategy, but effective immunization needs to overcome the patient’s immune tolerance against the self-HER2. Phage display technology, taking advantage of phage intrinsic immunogenicity, permits one to generate effective cancer vaccines able to break immune tolerance to self-antigens. In this study, we demonstrate that both preventive and therapeutic vaccination with M13 bacteriophages, displaying the extracellular (EC) and transmembrane (TM) domains of human HER2 or its Δ16HER2 splice variant on their surface (ECTM and Δ16ECTM phages), delayed mammary tumor onset and reduced tumor growth rate and multiplicity in ∆16HER2 transgenic mice, which are tolerant to human ∆16HER2. This antitumor protection correlated with anti-HER2 antibody production. The molecular mechanisms underlying the anticancer effect of vaccine-elicited anti-HER2 antibodies were analyzed in vitro against BT-474 human breast cancer cells, sensitive or resistant to trastuzumab. Immunoglobulins (IgG) purified from immune sera reduced cell viability mainly by impairing ERK phosphorylation and reactivating retinoblastoma protein function in both trastuzumab-sensitive and -resistant BT-474 cells. In conclusion, we demonstrated that phage-based HER2 vaccines impair mammary cancer onset and progression, opening new perspectives for HER2+ breast cancer treatment.
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- 2022
23. Preliminary ex vivo and in vivo evaluation of laser bonding in dura mater
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Francesca Rossi, Giada Magni, Roberto Colasanti, Martina Banchelli, Maurizio Iacoangeli, Erika Carrassi, Denis Aiudi, Alessandro Di Rienzo, Alessandra Marini, Luca Giannoni, Laura Pieri, Fiorenza Orlando, Mauro Provinciali, Stefano Dallari, and Paolo Matteini
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- 2022
24. Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model
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Mauro Provinciali, Elisa Molinelli, Oriana Simonetti, Gaia Goteri, Elżbieta Kamysz, Guendalina Lucarini, Annamaria Offidani, Giulio Rizzetto, Fiorenza Orlando, Andrea Giacometti, Wojciech Kamysz, Oscar Cirioni, Roberto Ghiselli, and Gianluca Morroni
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Microbiology (medical) ,Pathology ,medicine.medical_specialty ,Microbiological culture ,Angiogenesis ,medicine.medical_treatment ,wound ,RM1-950 ,medicine.disease_cause ,Biochemistry ,Microbiology ,Article ,Cathelicidin ,cathelicidin ,medicine ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Teicoplanin ,business.industry ,Granulation tissue ,LL-37 ,Surgical wound ,Antimicrobial ,VEGF ,animal models ,Infectious Diseases ,medicine.anatomical_structure ,Staphylococcus aureus ,Therapeutics. Pharmacology ,business ,medicine.drug - Abstract
Background: LL-37 is the only human antimicrobial peptide that belongs to the cathelicidins. The aim of the study was to evaluate the efficacy of LL-37 in the management of MRSA-infected surgical wounds in mice. Methods: A wound on the back of adult male BALB/c mice was made and inoculated with Staphylococcus aureus. Two control groups were formed (uninfected and not treated, C0, infected and not treated, C1) and six contaminated groups were treated, respectively, with: teicoplanin, LL-37, given topically and /or systemically. Histological examination of VEGF expression and micro-vessel density, and bacterial cultures of wound tissues, were performed. Results: Histological examination of wounds in the group treated with topical and intraperitoneal LL-37 showed increased re-epithelialization, formation of the granulation tissue, collagen organization, and angiogenesis. Conclusions: Based on the mode of action, LL-37 has a potential future role in the management of infected wounds.
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- 2021
25. LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice
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Antonio D'Amato, Marco Malavolta, Anna Ferrario, Francesco Villa, Francesca Iannone, Paolo Madeddu, Francesco De Rango, Annibale Alessandro Puca, Mauro Provinciali, Elena Ciaglia, Giuseppe Passarino, Albino Carrizzo, Andrea Basso, Serena Dato, Carmine Vecchione, Giuseppina Rose, Anna Maciag, and Fiorenza Orlando
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Longevity-Associated Variant-LAV ,Male ,Genotype ,Aging ,BPIFB4 ,Frailty ,Survival ,Longevity ,Population ,Mice, Transgenic ,frailty ,survival ,Mice ,medicine ,Animals ,Humans ,Endothelial dysfunction ,education ,Inverse correlation ,Gene ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Haplotype ,aging ,Correction ,Cell Biology ,Phosphoproteins ,medicine.disease ,Specific Pathogen-Free Organisms ,Mice, Inbred C57BL ,Gene Expression Regulation ,Genetic marker ,Cohort ,Immunology ,Intercellular Signaling Peptides and Proteins ,Female ,Risk of death ,business ,longevity-associated variant-lav ,Research Paper - Abstract
BACKGROUND:There is an increasing concern about age-related frailty because of the growing number of elderly people in the general population. The Longevity-Associated Variant (LAV) of the human BPIFB4 gene was found to correct endothelial dysfunction, one of the mechanisms underlying frailty, in aging mice whereas the RV-BPIFB4 variant induced opposite effects. Thus, we newly hypothesize that, besides being associated with life expectancy, BPIFB4 polymorphisms can predict frailty.Aim and Results: Here we investigated if the BPIFB4 haplotypes, LAV, wild-type (WT) and RV, differentially associate with frailty in a cohort of 237 elderly subjects from Calabria region in Southern Italy. Moreover, we studied the effect of systemic adeno-associated viral vector-mediated LAV-BPIFB4 gene transfer on the progression of frailty in aging mice. We found an inverse correlation of the homozygous LAV-BPIFB4 haplotype with frailty in elderly subjects. Conversely, carriers of the RV-BPIFB4 haplotype showed an increase in the frailty status and risk of death. Moreover, in old mice, LAV-BPIFB4 gene transfer delayed frailty progression.CONCLUSIONS:These data indicate that specific BPIFB4 haplotypes could represent useful genetic markers of frailty. In addition, horizontal transfer of a healthy gene variant can attenuate frailty in aging organisms.
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- 2019
26. Recovery from mild Escherichia coli O157:H7 infection in young and aged C57BL/6 mice with intact flora estimated by fecal shedding, locomotor activity and grip strength
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Fiorenza Orlando, Marco Malavolta, Maurizio Cardelli, Khadija Benlhassan, Serena Chierichetti, Francesca Leoni, Andrea Basso, Mauro Provinciali, Dorothy Bray, Elisa Pierpaoli, and Robertina Giacconi
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C57BL/6 ,Aging ,Flora ,medicine.drug_class ,Movement ,Immunology ,Antibiotics ,Physiology ,Oxytetracycline ,Escherichia coli O157 ,medicine.disease_cause ,Microbiology ,Foodborne Diseases ,Feces ,Mice ,Grip strength ,medicine ,Animals ,Immunology and Allergy ,Longitudinal Studies ,Pathogen ,Escherichia coli ,Escherichia coli Infections ,Hand Strength ,General Veterinary ,biology ,General Medicine ,biology.organism_classification ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Disease Models, Animal ,Infectious Diseases ,medicine.drug - Abstract
Escherichia coli 0157:H7 is a food-borne pathogen that can cause severe complications in vulnerable populations. Mouse infection models of E. coli 0157:H7 are usually developed under severe animal suffering classification by depleting the normal flora, in which age plays a role. Objective To develop a refined method for longitudinal monitoring of E. coli 0157:H7 in young and old mice with intact flora. Methods We applied discriminant analysis and computed composite standardized scores from 19 variables obtained from physiological parameters, analysis of locomotor activity, grip strength measurement and fecal shedding in 16 aged and 16 young C57BL/6 mice after two mild oral challenges of E. coli 0157:H7. The resulting scores were validated in another experiment performed in 24 aged and 24 young mice including a group (8 aged and 8 young mice) treated with oxytetracycline. Results We show that our scores are significantly affected in the post-infection period and that can be used to measure and compare the recovery time after a treatment. The scores are most sensitive when separately developed in young and aged mice. Conclusions We developed a method that minimizes the level of animal suffering and that can be applied in preclinical testing of new therapies.
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- 2019
27. Antimetastatic and Antitumor Activities of Orally Administered NAX014 Compound in a Murine Model of HER2-Positive Breast Cancer
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Carmela Salvatore, Mauro Provinciali, Gaetano Fiorillo, Paolo Lombardi, Fiorenza Orlando, Cristina Geroni, Elisa Pierpaoli, and Francesco Piacenza
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senescence ,Cell ,Berberine Alkaloids ,Administration, Oral ,p16 ,migration ,lcsh:Chemistry ,chemistry.chemical_compound ,Mice ,Berberine ,Cell Movement ,berberine ,Medicine ,NAX014 ,Neoplasm Metastasis ,lcsh:QH301-705.5 ,Spectroscopy ,Molecular Structure ,Alkaloid ,Brief Report ,lung metastases ,General Medicine ,VEGF ,Computer Science Applications ,Neoplasm Proteins ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Toxicity ,Female ,Genetically modified mouse ,Senescence ,Antineoplastic Agents ,Mice, Transgenic ,Catalysis ,Inorganic Chemistry ,breast cancer ,Cell Line, Tumor ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,business.industry ,Organic Chemistry ,Mammary Neoplasms, Experimental ,Cell Cycle Checkpoints ,Genes, erbB-2 ,In vitro ,Rats ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,HER-2 ,TNF-α ,Cancer cell ,Cancer research ,Drug Screening Assays, Antitumor ,business - Abstract
The natural isoquinoline alkaloid Berberine (BBR) has been shown to possess several therapeutic effects, including anticancer activity. Different BBR derivatives have been designed and synthesized in order to obtain new compounds with enhanced anticancer efficacy. We previously showed that intraperitoneal (IP) administration of the BBR-derived NAX014 compound was able to counteract HER-2 overexpressing mammary tumors onset and progression in transgenic mice. However, the IP administration was found to induce organ toxicity at doses higher than 2.5 mg/Kg. In this study, we evaluated the effect of intragastric (IG) administration of 20 mg/kg of NAX014 on both safety and anticancer efficacy in HER-2/neu transgenic mice. Furthermore, cancer cell dissemination and migration, tumor cell senescence and immunological changes were examined. Our results demonstrated that IG NAX014 administration delayed the onset of mammary tumors with no negative effects on health and survival. NAX014 reduced HER-2 overexpressing BC cells migration in vitro and the frequency of lung metastasis in HER-2/neu transgenic mice. A statistically significant increase of senescence-associated p16 expression was observed in tumors from NAX014-treated mice, and the induction of cell senescence was observed in HER-2 overexpressing BC cells after in vitro treatment with NAX014. Although NAX014 did not modulate the presence of tumor-infiltrating lymphocytes, the level of circulating TNF-α and VEGF was found to be reduced in NAX014-treated mice. The overall results address the NAX014 compound as potential tool for therapeutic strategies against HER-2 overexpressing breast cancer.
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- 2021
28. RNA-mediated gene silencing of nicotinamide N-methyltransferase is associated with decreased tumorigenicity in human oral carcinoma cells.
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Valentina Pozzi, Davide Sartini, Stefano Morganti, Rachela Giuliante, Giulia Di Ruscio, Andrea Santarelli, Romina Rocchetti, Corrado Rubini, Marco Tomasetti, Giovanni Giannatempo, Fiorenza Orlando, Mauro Provinciali, Lorenzo Lo Muzio, and Monica Emanuelli
- Subjects
Medicine ,Science - Abstract
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. Despite progress in the treatment of OSCC, overall survival has not improved substantially in the last three decades. Therefore, identification of reliable biomarkers becomes essential to develop effective anti-cancer therapy. In this study, we focused on the enzyme Nicotinamide N-methyltransferase (NNMT), which plays a fundamental role in the biotransformation of many xenobiotics. Although several tumors have been associated with abnormal NNMT expression, its role in cancer cell metabolism remains largely unknown. In this report, 7 human oral cancer cell lines were examined for NNMT expression by Real-Time PCR, Western blot and HPLC-based catalytic assay. Subsequently, we evaluated the in vitro effect of shRNA-mediated silencing of NNMT on cell proliferation. In vivo tumorigenicity of oral cancer cells with stable knockdown of NNMT was assayed by using xenograft models. High expression levels of NNMT were found in PE/CA PJ-15 cells, in keeping with the results of Western blot and catalytic activity assay. PE/CA PJ-15 cell line was stably transfected with shRNA plasmids against NNMT and analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and soft agar Assays. Transfected and control cells were injected into athymic mice in order to evaluate the effect of NNMT silencing on tumor growth. NNMT downregulation resulted in decreased cell proliferation and colony formation ability on soft agar. In athymic mice, NNMT silencing induced a marked reduction in tumour volume. Our results show that the downregulation of NNMT expression in human oral carcinoma cells significantly inhibits cell growth in vitro and tumorigenicity in vivo. All these experimental data seem to suggest that NNMT plays a critical role in the proliferation and tumorigenic capacity of oral cancer cells, and its inhibition could represent a potential molecular approach to the treatment of oral carcinoma.
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- 2013
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- View/download PDF
29. A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis
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Michele Riccio, Barbara Zavan, Nicola Zingaretti, Valentina Riccio, Andrea Marchesini, Fiorenza Orlando, Monica Mattioli-Belmonte, and Francesco De Francesco
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adhesion (medicine) ,Connective tissue ,scar ,wound model ,Cell and Developmental Biology ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,medicine ,Deformity ,Pathological ,lcsh:QH301-705.5 ,Subcutaneous fibrosis ,Original Research ,business.industry ,animal model ,talc ,Cell Biology ,medicine.disease ,Tendon ,pathological fibrosis ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Immunohistochemistry ,medicine.symptom ,business ,Developmental Biology - Abstract
Fibrosis is a condition that affects the connective tissue in an organ or tissue in the restorative or responsive phase as a result of injury. The consequences of excessive fibrotic tissue growth may lead to various physiological complications of deformity and impairment due to hypertrophic scars, keloids, and tendon adhesion without understating the psychological impact on the patient. However, no method accurately quantifies the rate and pattern of subcutaneous induced hypertrophic fibrosis. We, therefore, devised a rodent excisional model to evaluate the extent of fibrosis with talc. Tissue specimens were set on formalin, and paraffin sections for histological, immunohistochemical, and molecular analysis talc was used to induce the fibroproliferative mechanism typical of hypertrophic scars. This pathway is relevant to the activation of inflammatory and fibrotic agents to stimulate human hypertrophic scarring. This model reproduces morpho-functional features of human hypertrophic scars to investigate scar formation and assess potential anti-scarring therapies.
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- 2020
30. New Evidence and Insights on Dalbavancin and Wound Healing in a Mouse Model of Skin Infection
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Lucia Brescini, Mauro Provinciali, Fiorenza Orlando, Raffaella Lazzarini, Oscar Cirioni, Annamaria Offidani, Oriana Simonetti, Andrea Giacometti, Gianluca Morroni, Antonio Zizzi, and Guendalina Lucarini
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Vascular Endothelial Growth Factor A ,Staphylococcus aureus ,medicine.drug_class ,Antibiotics ,Pharmacology ,Skin infection ,medicine.disease_cause ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Vancomycin ,Matrix Metalloproteinase 13 ,Animals ,Surgical Wound Infection ,Medicine ,Pharmacology (medical) ,Mechanisms of Action: Physiological Effects ,030304 developmental biology ,Mice, Inbred BALB C ,Wound Healing ,0303 health sciences ,integumentary system ,030306 microbiology ,business.industry ,Dalbavancin ,Granulation tissue ,medicine.disease ,Bacterial Load ,Anti-Bacterial Agents ,ErbB Receptors ,Vascular endothelial growth factor ,Disease Models, Animal ,Infectious Diseases ,medicine.anatomical_structure ,Matrix Metalloproteinase 9 ,chemistry ,Staphylococcal Skin Infections ,Teicoplanin ,business ,Wound healing ,medicine.drug - Abstract
Dalbavancin is an effective antibiotic that is widely used to treat skin infection. Our aim was to determine the effect of dalbavancin administration on wound healing compared to that of vancomycin and to elucidate if epidermal growth factor receptor (EGFR), matrix metalloproteinase 1 (MMP-1), MMP-9, and vascular endothelial growth factor (VEGF) could be involved in its therapeutic mechanism. A mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection was established. Mice were treated daily with vancomycin (10 mg/kg) and weekly with dalbavancin at day 1 (20 mg/kg) and day 8 (10 mg/kg). After 14 days, wounds were excised, and bacterial counts were performed. Wound healing was assessed by histological and immunohistochemical staining, followed by protein extraction and immunoblotting. Our microbiological results confirmed that both dalbavancin and vancomycin are effective in reducing the bacterial load in wounds. The dalbavancin group showed a strong effect compared with infected untreated animals and the vancomycin-treated group. The wounds treated with dalbavancin showed robust epidermal coverage with reconstitution of the regular and keratinized epidermal lining and well-organized granulation tissue with numerous blood vessels, although slightly less than that in the uninfected group. While in the vancomycin-treated group the epithelium appeared, in general, still hypertrophic, the granulation tissue appeared even less organized. We observed elevated EGFR and VEGF expression in both treated groups, although it was higher in dalbavancin-treated mice. MMP-1 and MMP-9 were decreased in uninfected tissue and in both treated tissues compared with untreated infected wounds. This study showed faster healing with dalbavancin treatment that might be associated with higher EGFR and VEGF levels.
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- 2020
31. Erratum: Correction of Affiliation
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Eleonora Salvolini, Guendalina Lucarini, Mario Guerrieri, Fabio Casciani, Roberto Ghiselli, Mauro Provinciali, Fiorenza Orlando, Stefania Saccomanno, and Monica Ortenzi
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Non-steroidal inflammatory drugs ,medicine.medical_specialty ,Histology ,MMP9 ,business.industry ,General surgery ,colo-colic anastomosis ,Rat model ,Biophysics ,Drug administration ,wound healing ,Review ,Cell Biology ,lcsh:Biology (General) ,inflammation ,Medicine ,peritonitis ,business ,lcsh:QH301-705.5 - Abstract
This corrects the article "Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration " in volume 64(1):3085 In the published article “Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration” Eur J Histochem 2020;64(1):3085, https://doi.org/10.4081/ejh.2020.3085,” one affiliation was published incorrectly. The authors apologize for any inconvenience that it may have caused. Roberto Ghiselli,1 Guendalina Lucarini,2 Monica Ortenzi,1 Eleonora Salvolini,3 Stefania Saccomanno,2 Fiorenza Orlando,4 Mauro Provinciali,4 Fabio Casciani,1 Mario Guerrieri1 1Clinic of Surgery, Marche Polytechnic University, Ancona2Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona3Department of Odontostomatologic and Specialized Clinical Sciences, Marche Polytechnic University, Ancona4Experimental Animal Models for Aging Units, Research Department, Italian National Institute on Aging (INRCA) IRCCS, Ancona, Italy The affiliation should be corrected as follows: 4Experimental Animal Models for Aging Units, Scientific Technological Area, IRCCS INRCA, Ancona, Italy
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- 2020
32. Preliminary ex vivo and in vivo evaluation of laser bonding in dura mater
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Filippo Fagnani, Fiorenza Orlando, Roberto Pini, Massimo Scerrati, Fulvio Ratto, Mauro Provinciali, Luca Giannoni, Erika Carrassi, Alessandro Di Rienzo, Paolo Matteini, Francesca Rossi, Maurizio Iacoangeli, Stefano Dallari, Denis Aiudi, Roberto Colasanti, Laura Pieri, Giada Magni, and Alessandra Marini
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ICG ,musculoskeletal diseases ,Materials science ,integumentary system ,Dura mater ,Thermal effect ,dura mater repair ,chitosan patch ,musculoskeletal system ,Laser ,Laser assisted ,law.invention ,chemistry.chemical_compound ,laser bonding ,medicine.anatomical_structure ,nervous system ,chemistry ,law ,In vivo ,medicine ,Laser bonding ,Indocyanine green ,Ex vivo ,Biomedical engineering - Abstract
Dura mater repair represents a final and crucial step in cranial surgery: an inadequate dural reconstruction determines dreadful consequences that significantly increase morbidity and mortality rates. Different dural substitutes have been used with poor results. To overcome this issue, in previous studies we proposed a laser-based approach to the bonding of porcine dura mater, evidencing the feasibility of the laser assisted procedure. In this work, we present the optimization of the laser bonding approach ex vivo in porcine dura mater and in vivo in rats. An 810 nm cw laser was used to weld the ICG stained chitosan patch to the dura. The ex vivo tests enabled to optimize the laser parameters, using histology and leak pressure evaluation to study the bonding effect. The in vivo tests were performed on 32 adult Wistar rats: laser bonding was carried out in 16 rats, while a collagen matrix was used for duroplasty in the control group. After the treatment, the animals were left to recover and were observed in a 15 and 90 days follow up study. At sacrifice, the rats were anesthetized for fluid leakage pressure test; treated tissue was harvested and underwent standard histology. The results of this study pointed out that the laser bonding procedure can be used to close the dura mater, both ex vivo and in vivo. The thermal effect is limited and spatially confined. The technique can thus be proposed as a valid alternative to standard method for the closuring of dura mater in cranial surgery.
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- 2020
33. Potential application of berberine in the treatment of
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Elisa, Pierpaoli, Oscar, Cirioni, Oriana, Simonetti, Fiorenza, Orlando, Andrea, Giacometti, Paolo, Lombardi, and Mauro, Provinciali
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Mice ,Berberine ,Sepsis ,Escherichia coli ,Animals - Abstract
Gram-negative sepsis ranks as the leading cause of death in intensive care units. Despite the development of new antibiotics, mortality from gram-negative sepsis remains high. The present study aims to investigate the
- Published
- 2020
34. Anastomotic healing in a rat model of peritonitis after non-steroidal anti-inflammatory drug administration
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Mauro Provinciali, Monica Ortenzi, Fiorenza Orlando, Fabio Casciani, Guendalina Lucarini, Stefania Saccomanno, Roberto Ghiselli, Mario Guerrieri, and Eleonora Salvolini
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Diclofenac ,Histology ,colo-colic anastomosis ,Biophysics ,Peritonitis ,Anastomotic Leak ,wound healing ,Anastomosis ,Gastroenterology ,Article ,Sepsis ,03 medical and health sciences ,chemistry.chemical_compound ,Hydroxyproline ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Surgical Wound Dehiscence ,medicine ,Animals ,Rats, Wistar ,peritonitis ,Cecum ,Sirius Red ,lcsh:QH301-705.5 ,Non-steroidal inflammatory drugs ,business.industry ,MMP9 ,Anastomosis, Surgical ,Anti-Inflammatory Agents, Non-Steroidal ,Cell Biology ,medicine.disease ,digestive system diseases ,Ketorolac ,030104 developmental biology ,Matrix Metalloproteinase 9 ,chemistry ,lcsh:Biology (General) ,inflammation ,030220 oncology & carcinogenesis ,business ,Wound healing ,medicine.drug - Abstract
The tissue inflammatory response can influence the outcome of anastomotic healing. Anastomotic leakage represents a dreadful complication after gastrointestinal surgery, in particular sepsis and intra-abdominal infections impair the restorative process of colic anastomoses. It has been debated whether the administration of non-steroidal anti-inflammatory drugs (NSAIDs) is a risk factor for dehiscence, since many patients receive NSAIDs in the early postoperative period. Our aim was, for the first time, to analyze the morpho-functional effects of postoperative administration of two commonly used NSAIDs, Diclofenac and Ketorolac, on the healing process of colo-colic anastomoses constructed under condition of fecal peritonitis in a rat model. Sixty adult male rats underwent two surgical procedures: peritonitis induction and colo-colic anastomosis, and were divided into three groups: 20 rats received saline; 20 rats 4 mg/kg Diclofenac and 20 rats 5 mg/kg Ketorolac. We assessed anastomosis strength, morphological features of tissue wound healing, immunohistochemical metalloproteinase 9 (MMP9) expression and collagen deposition and content by Sirius red staining and hydroxyproline level. We found no significant difference in bursting pressure, collagen content and organization and morphological features between the groups, except a significantly reduced presence of inflammatory cells and MMP9 expression in the groups treated with NSAIDs. Our findings showed that Diclofenac and Ketorolac administration did not affect post-surgical healing and did not increase the leakage risk of colo-colic anastomoses during peritonitis.
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- 2020
35. Increase of n-NOS and i-NOS in Rat Colon After Sacral Neuromodulation
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Guendalina Lucarini, Roberto Ghiselli, Luca Cardinali, Mario Guerrieri, Roberto Di Primio, Monica Ortenzi, Fiorenza Orlando, and Mauro Provinciali
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Sacrum ,Pathology ,medicine.medical_specialty ,Colon ,Nitric Oxide Synthase Type II ,Rectum ,Stimulation ,Nitric Oxide Synthase Type I ,Nitric oxide ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Western blot ,Neuromodulation ,medicine ,Animals ,Myocyte ,medicine.diagnostic_test ,business.industry ,General Medicine ,Electric Stimulation ,Rats ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Neurology ,chemistry ,Mechanism of action ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,030211 gastroenterology & hepatology ,Neurology (clinical) ,medicine.symptom ,business - Abstract
OBJECTIVE Sacral neuromodulation (SNM) is proposed to treat different anorectal dysfunctions but its mechanism of action is not yet known. Our previous study demonstrated how SNM can significantly increase neuronal nitric oxide synthase NOS (n-NOS) and inducible NOS (i-NOS) expression in the anus and rectum of rats. There are no reports regarding the relation between SNM and NOS in colonic cells: our aim was to assess NOS expression in colonic rat model after SNM. MATERIALS AND METHODS Twenty-six female Sprangue-Dawley rats were considered: group I, normal control rats; group II, sham treatment rats, in whom electrodes for electrical stimulation were placed in S1 foramen bilaterally and left in place, without performing neuromodulation; group III, rats in whom SNM was performed. After 14 days, the rats were sacrificed and we evaluated n-NOS and i-NOS in colonic specimens by immunohistochemistry and Western Blot analysis. RESULTS Western Blot analysis showed that levels of n-NOS and i-NOS were higher in colon of the III group rats respect to the others; in particular, immunohistochemistry revealed that, after neuromodulation, n-NOS expression in the muscle cells and i-NOS expression in glandular epithelium and nervous cells were highly represented (p
- Published
- 2017
36. Colistin enhances therapeutic efficacy of daptomycin or teicoplanin in a murine model of multiresistant Acinetobacter baumannii sepsis
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Maria Michela Cappelletti Trombettoni, Mauro Provinciali, Alessandra Barucca, Oriana Simonetti, Fiorenza Orlando, Oscar Cirioni, Maria Pelloni, Annamaria Offidani, Roberto Ghiselli, Mario Guerrieri, Andrea Giacometti, and Elisa Pierpaoli
- Subjects
Acinetobacter baumannii ,Male ,0301 basic medicine ,Microbiology (medical) ,030106 microbiology ,Microbial Sensitivity Tests ,Microbiology ,Sepsis ,03 medical and health sciences ,Daptomycin ,In vivo ,Drug Resistance, Multiple, Bacterial ,polycyclic compounds ,medicine ,Animals ,In vitro study ,Mice, Inbred BALB C ,biology ,Colistin ,Teicoplanin ,business.industry ,Drug Synergism ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Survival Analysis ,Anti-Bacterial Agents ,Disease Models, Animal ,Treatment Outcome ,Infectious Diseases ,Murine model ,bacteria ,Drug Therapy, Combination ,lipids (amino acids, peptides, and proteins) ,business ,Acinetobacter Infections ,medicine.drug - Abstract
We investigated the efficacy of colistin combined with teicoplanin or daptomycin in an experimental mouse model of multiresistant Acinetobacter baumannii infection. Animal received intraperitoneally 1ml saline containing 2×1010CFU of A. baumannii. Colistin, daptomycin, teicoplanin, and colistin plus daptomycin or teicoplanin were given by intraperitoneal administration 2h after bacterial challenge. A control group received sodium chloride solution. In the in vitro study A. baumannii showed to be susceptible only to colistin with MIC of 2mg/l. In the in vivo study, colistin alone showed a good antimicrobial efficacy. When combined with teicoplanin or daptomycin, colistin produced the lowest bacterial and the best survival rates. In immunological studies, when colistin was associated to daptomycin or teicoplanin, both the number and the cytotoxic activity of NK cells increased. In conclusion, colistin combined with teicoplanin or daptomycin may improve the therapy of multiresistant A. baumannii infection.
- Published
- 2016
37. Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin
- Author
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Mauro Provinciali, Silvia Agarbati, Armando Gabrielli, Martino Introna, A. Grieco, Chiara Paolini, Chiara Capelli, Fiorenza Orlando, Gianluca Moroncini, and C. Tonnini
- Subjects
Pathology ,medicine.medical_specialty ,General Chemical Engineering ,Pulmonary Fibrosis ,Lung injury ,Bleomycin ,Mesenchymal Stem Cell Transplantation ,General Biochemistry, Genetics and Molecular Biology ,Umbilical Cord ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Fibrosis ,In vivo ,Pulmonary fibrosis ,Medicine ,Animals ,0303 health sciences ,General Immunology and Microbiology ,business.industry ,General Neuroscience ,030305 genetics & heredity ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Lung Injury ,respiratory system ,medicine.disease ,Pathophysiology ,respiratory tract diseases ,Mice, Inbred C57BL ,Trachea ,Disease Models, Animal ,chemistry ,Systemic administration ,Female ,business - Abstract
Pulmonary fibrosis is a hallmark of several human lung diseases with a different etiology. Since current therapies are rather limited, mouse models continue to be an essential tool for developing new antifibrotic strategies. Here we provide an effective method to investigate in vivo antifibrotic activity of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC) in attenuating bleomycin-induced lung injury. C57BL/6 mice receive a single endotracheal injection of bleomycin (1.5 U/kg body weight) followed by a double infusion of hUC-MSC (2.5 x 105) into the tail vein, 24 h and 7 days after the bleomycin administration. Upon sacrifice at days 8, 14, or 21, inflammatory and fibrotic changes, collagen content, and hUC-MSC presence in explanted lung tissue are analyzed. The injection of bleomycin into the mouse trachea allows the direct targeting of the lungs, leading to extensive pulmonary inflammation and fibrosis. The systemic administration of a double dose of hUC-MSC results in the early blunting of the bleomycin-induced lung injury. Intravenously infused hUC-MSC are transiently engrafted into the mouse lungs, where they exert their anti-inflammatory and antifibrotic activity. In conclusion, this protocol has been successfully applied for the preclinical testing of hUC-MSC in an experimental mouse model of human pulmonary fibrosis. However, this technique can be easily extended both to study the effect of different endotracheally administered substances on the pathophysiology of the lungs and to validate new anti-inflammatory and antifibrotic systemic therapies.
- Published
- 2019
38. Ageing-related expression of Twinfilin-1 regulates cholangiocyte biological response to injury
- Author
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Ibone Labiano, Jesus M. Banales, Stefania Saccomanno, Luciano Trozzi, Malgorzata Milkiewicz, Espen Melum, Debora Maria Giordano, Chiara Rychlicki, Maria Cristina Albertini, Marina Scarpelli, Luca Maroni, Gianluca Svegliati Baroni, Piotr Milkiewicz, Antonio Benedetti, Marco Marzioni, Mauro Provinciali, Daniele Spallacci, Fiorenza Orlando, and C. Pinto
- Subjects
0301 basic medicine ,Senescence ,Aging ,Cholangitis, Sclerosing ,Biology ,Sensitivity and Specificity ,Cholangiocyte ,03 medical and health sciences ,Mice ,Random Allocation ,0302 clinical medicine ,Fibrosis ,In vivo ,microRNA ,medicine ,Animals ,Humans ,Biliary Tract ,Cells, Cultured ,Cellular Senescence ,Cell Proliferation ,Hepatology ,Cell growth ,Microfilament Proteins ,medicine.disease ,Phenotype ,Disease Models, Animal ,MicroRNAs ,030104 developmental biology ,Cancer research ,030211 gastroenterology & hepatology ,Intracellular - Abstract
Disorders of the biliary tree develop and progress differently according to patient age. It is currently not known whether the aging process affects the response to injury of cholangiocytes. The aim of this study was to identify molecular pathways associated with cholangiocyte aging and to determine their effects in the biological response to injury of biliary cells. A panel of microRNAs (miRs) involved in aging processes was evaluated in cholangiocytes of young and old mice (2 months and 22 months of age, respectively) and subjected to a model of sclerosing cholangitis. Intracellular pathways that are common to elevated miRs were identified by in silico analysis. Cell proliferation and senescence were evaluated in Twinfilin-1 (Twf1) knocked-down cells. In vivo, senescence-accelerated prone mice (Samp8, a model for accelerated aging), Twf1-/- , or their respective controls were subjected to DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine). Cholangiocytes from DDC-treated mice showed up-regulation of a panel of aging-related miRs. Twf1 was identified by in silico analysis as a common target of the up-regulated miRs. Twf1 expression was increased both in aged and diseased cholangiocytes, and in human cholangiopathies. Knock-down of Twf1 in cholangiocytes reduced cell proliferation. Senescence and senescence-associated secretory phenotype marker expression increased in Twf1 knocked-down cholangiocytes following pro-proliferative and pro-senescent (10-day lipopolysaccharide) stimulation. In vivo, Samp8 mice showed increased biliary proliferation, fibrosis, and Twf1 protein expression level, whereas Twf1-/- had a tendency toward lower biliary proliferation and fibrosis following DDC administration compared with control animals. Conclusion: We identified Twf1 as an important mediator of both cholangiocyte adaptation to aging processes and response to injury. Our data suggest that disease and aging might share common intracellular pathways.
- Published
- 2019
39. Effect of hyperglycemia on the number of CD117+ progenitor cells and their differentiation toward endothelial progenitor cells in young and old ages
- Author
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Marco Malavolta, Raffaella Moresi, Fiorenza Orlando, Mauro Provinciali, and Elisa Pierpaoli
- Subjects
0301 basic medicine ,Aging ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,medicine ,Progenitor cell ,biology ,CD117 ,business.industry ,Diabetic mouse ,medicine.disease ,Phenotype ,digestive system diseases ,In vitro ,030104 developmental biology ,Endocrinology ,Cell culture ,Immunology ,biology.protein ,business ,Developmental Biology ,Lipoprotein - Abstract
Dysfunction of endothelial progenitor cells (EPCs) has been reported either in aging or diabetes, though the influence of an "old" environment on numerical and functional changes of diabetes associated EPCs is not known. We evaluated the effect of both aging and early stage of streptozotocin-induced diabetes on the number of bone marrow-derived CD117+ progenitor cells, and on their differentiation in vitro toward EPCs. The phenotype of progenitor cells and the uptake of acetylated-low density lipoprotein (Ac-LDL) were evaluated after cell culture in VEGF, FGF-1, and IGF-1 supplemented medium. Hyperglycemia similarly reduced the number of CD117+ cells both in young and old mice. CD117+ cells from young mice differentiated better than those from old animals "in vitro", with a greater reduction of CD117+ cells and an higher increase of CD184+VEGFR-2+ cells. In diabetic mice, in vitro CD117+ cells differentiation was significantly reduced in young animals. Diabetes did not impact on the scarce differentiation of CD117+ cells from old mice. Hyperglycemia reduced the uptake of acLDL by EPCs greatly in young than in old mice. These findings indicate that part of the EPCs functional alterations induced by hyperglicemia in young mice are observed in normal aged mice.
- Published
- 2016
40. Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis
- Author
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Andrea Giacometti, Daniele Minardi, Oriana Simonetti, Maria Pelloni, Annamaria Offidani, Mario Guerrieri, Maria Michela Cappelletti Trombettoni, Oscar Cirioni, Elisa Pierpaoli, Mauro Provinciali, Roberto Ghiselli, Fiorenza Orlando, and Alessandra Barucca
- Subjects
Acinetobacter baumannii ,Male ,0301 basic medicine ,medicine.medical_treatment ,030106 microbiology ,Pharmacology ,Critical Care and Intensive Care Medicine ,Bacterial counts ,Immunophenotyping ,Sepsis ,Mice ,03 medical and health sciences ,In vivo ,polycyclic compounds ,medicine ,Animals ,Saline ,Mice, Inbred BALB C ,biology ,Colistin ,business.industry ,Positive interaction ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,030104 developmental biology ,Emergency Medicine ,bacteria ,lipids (amino acids, peptides, and proteins) ,business ,Bacteria ,Antimicrobial Cationic Peptides ,medicine.drug - Abstract
We investigated the efficacy of colistin combined with pexiganan in experimental mouse models of Acinetobacter baumannii infection.Adult male BALB/c mice received intraperitoneally 1 mL saline containing 2 × 10 CFU of susceptible and multiresistant A. baumannii. Two hours after bacterial challenge, animals received 1 mg/kg of colistin, 1 mg/kg of pexiganan, or 1 mg/kg of colistin plus 1 mg/kg of pexiganan.Blood culture positivity, the quantities of bacteria in the intra-abdominal fluid, the rate of lethality and immunological studies, such as immunophenotyping and NK cytotoxicity, were evaluated.In the in vitro study, A. baumannii showed susceptibility to colistin and pexiganan and a strong synergy was observed by testing colistin combined with pexiganan with fractionary inhibitory concentration index of 0.312 for both strains.In the in vivo study colistin or pexiganan alone showed a good antimicrobial efficacy. When colistin was combined with pexiganan, the positive interaction produced low bacterial counts that were statistically significant versus singly treated groups. For both strains the highest rate of survival was observed in combined-treated groups (90%).Pexiganan increased NK cytotoxic activity over the levels of infected and colistin-treated animals.In conclusion, pexiganan combined with colistin was found to be efficacious against A. baumannii infection.
- Published
- 2016
41. Efficacy of Pexiganan Combination with Tigecycline in a Mouse Model of Pseudomonas aeruginosa Sepsis
- Author
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Elżbieta Kamysz, Annamaria Offidani, Mauro Provinciali, Andrea Giacometti, Gianluca Morroni, Lucia Brescini, Fiorenza Orlando, Monia Orciani, Oriana Simonetti, Miriam Caffarini, Claudio Agostinelli, Elisa Pierpaoli, Oscar Cirioni, and Wojciech Kamysz
- Subjects
Male ,medicine.drug_class ,Cell Survival ,Antibiotics ,Antimicrobial peptides ,Tigecycline ,Microbial Sensitivity Tests ,medicine.disease_cause ,Azithromycin ,01 natural sciences ,Microbiology ,Mice ,Structure-Activity Relationship ,Antibiotic resistance ,Drug Resistance, Multiple, Bacterial ,Sepsis ,Drug Discovery ,medicine ,Animals ,Humans ,Cell Proliferation ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,business.industry ,Pseudomonas aeruginosa ,Broth microdilution ,General Medicine ,Antimicrobial ,0104 chemical sciences ,Anti-Bacterial Agents ,010404 medicinal & biomolecular chemistry ,Disease Models, Animal ,Drug Therapy, Combination ,business ,Injections, Intraperitoneal ,medicine.drug ,Antimicrobial Cationic Peptides ,HeLa Cells - Abstract
Background: Pseudomonas aeruginosa is a gram-negative pathogen, associated with a severe mortality rate. It is also difficult to treat due to numerous resistance mechanisms to a wide range of antibiotics. Objective: Evaluate the activity of pexiganan, an antimicrobial peptide, in combination with two clinical antibiotics (azithromycin and tigecycline) that are not active against P. aeruginosa. Methods: Ten clinical P. aeruginosa were isolated from urinary tract infections, blood culture, skin infections and respiratory tract infections. Minimum inhibitory concentrations (MICs) and synergies were evaluated by broth microdilution, checkerboard assays and time-kill studies. In vitro synergy was confirmed with an in vivo experiment using a murine model of sepsis. Results: Pexiganan MICs were included between 2 and 16 mg/L. Tigecycline and azithromycin MICs were high as expected (4-64 mg/L and 32-256 mg/L, respectively). Pexiganan and azithromycin combination resulted to be additive or indifferent while tigecycline and pexiganan combination was synergic against seven out of ten P. aeruginosa and additive against the other strains. In vivo experiment confirmed the in vitro synergy, denoting a significative reduction of bacteria in mice treated with pexiganan and tigecycline combination. Conclusion: Antimicrobial peptides are molecules that could be useful in the fight against infections and pexiganan seems to be one of the most promising. Our results demonstrated that, in association with tigecycline, pexiganan administration could overcome antibiotic resistance and increase the effectiveness of treatment against P. aeruginosa sepsis.
- Published
- 2018
42. In vitro and in vivo activity of fosfomycin alone and in combination with rifampin and tigecycline against Gram-positive cocci isolated from surgical wound infections
- Author
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Gianluca Morroni, Annamaria Offidani, Fiorenza Orlando, Oscar Cirioni, Mario Guerrieri, Andrea Giacometti, Mauro Provinciali, Roberto Ghiselli, Oriana Simonetti, Andrea Brenciani, and Ledia Xhuvelaj
- Subjects
0301 basic medicine ,Microbiology (medical) ,Male ,Methicillin-Resistant Staphylococcus aureus ,030106 microbiology ,Enterococcus faecium ,Minocycline ,Tigecycline ,Microbial Sensitivity Tests ,Biology ,Fosfomycin ,medicine.disease_cause ,Microbiology ,Enterococcus faecalis ,03 medical and health sciences ,Mice ,In vivo ,medicine ,Animals ,Humans ,Surgical Wound Infection ,Mice, Inbred BALB C ,Soft Tissue Infections ,General Medicine ,Skin Diseases, Bacterial ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Antimicrobial ,Anti-Bacterial Agents ,Gram-Positive Cocci ,Staphylococcus aureus ,Rifampin ,Rifampicin ,medicine.drug - Abstract
Complicated skin and soft tissue infections constitute a heterogeneous group of severe disorders, with surgical site infections being the most common hospital-acquired ones. The aim of our study was to investigate the synergistic and bactericidal activities of antimicrobial combinations of fosfomycin with rifampicin and tigecycline against Enterococcus faecalis, Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, and also to evaluate their in vivo effects in a mouse wound infection model. In in vitro studies, the combinations of fosfomycin with rifampicin and tigecycline were both synergistic. These synergies were confirmed in in vivo studies: the drug combinations showed the highest antimicrobial effects compared to monotherapy. In conclusion, the efficacy of fosfomycin combinations, also confirmed in our in vivo model, may suggest new directions in the treatment of infected skin and a possible alternative way to control bacterial skin infection.
- Published
- 2017
43. Metallothioneins, longevity and cancer: Comment on 'Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv mouse strain'
- Author
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Andrea Basso, Elisa Pierpaoli, L. Costarelli, Mauro Provinciali, Guendalina Lucarini, Francesco Piacenza, Robertina Giacconi, Marco Malavolta, and Fiorenza Orlando
- Subjects
Male ,0301 basic medicine ,Aging ,Mice, 129 Strain ,media_common.quotation_subject ,Longevity ,Cellular senescence ,Biology ,Biochemistry ,03 medical and health sciences ,Endocrinology ,Genetics ,medicine ,Animals ,Metallothionein ,Molecular Biology ,Gene ,media_common ,Strain (biology) ,Cancer ,Cell Biology ,medicine.disease ,Cell biology ,030104 developmental biology ,Female ,129/Sv Mouse - Published
- 2016
44. Role of Daptomycin on Burn Wound Healing in an Animal Methicillin-Resistant Staphylococcus aureus Infection Model
- Author
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Mario Guerrieri, Elisa Pierpaoli, Roberto Ghiselli, Andrea Giacometti, Mauro Provinciali, Annamaria Offidani, Oscar Cirioni, Pamela Castelli, Oriana Simonetti, Guendalina Lucarini, Roberto Di Primio, and Fiorenza Orlando
- Subjects
Male ,Methicillin-Resistant Staphylococcus aureus ,0301 basic medicine ,medicine.medical_specialty ,030106 microbiology ,Microbial Sensitivity Tests ,Fibroblast growth factor ,medicine.disease_cause ,Gastroenterology ,Cicatrix ,03 medical and health sciences ,Daptomycin ,In vivo ,Internal medicine ,Animals ,Medicine ,Pharmacology (medical) ,Rats, Wistar ,Mechanisms of Action: Physiological Effects ,Cell Proliferation ,Pharmacology ,Wound Healing ,business.industry ,Teicoplanin ,Epithelial Cells ,Staphylococcal Infections ,Methicillin-resistant Staphylococcus aureus ,Bacterial Load ,Thermal burn ,Anti-Bacterial Agents ,Rats ,ErbB Receptors ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Staphylococcus aureus ,Wound Infection ,Fibroblast Growth Factor 2 ,Burns ,Wound healing ,business ,medicine.drug - Abstract
Prolonged hospitalization and antibiotic therapy are risk factors for the development of methicillin-resistant Staphylococcus aureus (MRSA) infections in thermal burn patients. We used a rat model to study the in vivo efficacy of daptomycin in the treatment of burn wound infections by S. aureus , and we evaluated the wound healing process through morphological and immunohistochemical analysis. A copper bar heated in boiling water was applied on a paraspinal site of each rat, resulting in two full-thickness burns. A small gauze was placed over each burn and inoculated with 5 × 10 7 CFU of S. aureus ATCC 43300. The study included two uninfected control groups with and without daptomycin treatment, an infected control group that did not receive any treatment, and two infected groups treated, respectively, with intraperitoneal daptomycin and teicoplanin. The main outcome measures were quantitative culture, histological evaluation of tissue repair, and immunohistochemical expression of wound healing markers: epidermal growth factor receptor (EGFR) and fibroblast growth factor 2 (FGF-2). The highest inhibition of infection was achieved in the group that received daptomycin, which reduced the bacterial load from 10 7 CFU/ml to about 10 3 CFU/g ( P < 0.01). The groups treated with daptomycin showed better overall healing with epithelialization and significantly higher collagen scores than the other groups, and these findings were also confirmed by immunohistochemical data. In conclusion, our results support the hypothesis that daptomycin is an important modulator of wound repair by possibly reducing hypertrophic burn scar formation.
- Published
- 2017
45. Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
- Author
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Fiorenza Orlando, Mauro Provinciali, Alessandra Barucca, and Elisa Pierpaoli
- Subjects
0301 basic medicine ,Genetically modified mouse ,Receptor, ErbB-2 ,Science ,Transgene ,Immunization, Secondary ,Mice, Transgenic ,Adaptive Immunity ,Biology ,Cancer Vaccines ,Article ,Mice ,03 medical and health sciences ,Plasmid ,Antigens, Neoplasm ,030502 gerontology ,medicine ,Animals ,Cytotoxic T cell ,Immunity, Cellular ,Multidisciplinary ,Mammary Neoplasms, Experimental ,Cancer ,Immunosenescence ,medicine.disease ,Immunity, Humoral ,030104 developmental biology ,Immunization ,Immunoglobulin class switching ,Immunology ,Cancer research ,Medicine ,Female ,Immunotherapy ,0305 other medical science ,Plasmids - Abstract
Cancer vaccines are less effective at old than at young age because of immunosenescence. Besides, in preliminary observations we showed that the immunization with HER-2/neu DNA plasmid in transgenic young mice (standard immunization, SI) delays but not abrogate spontaneous mammary tumours progressively appearing during aging. In this study we evaluated whether booster immunizations (BI) of HER-2/neu transgenic mice with HER-2/neu DNA plasmids every 6 (ECD6), 3 (ECD3), or 1.5 (ECD1.5) months after SI induce a protective immunity that could be maintained over life span. The long term BI significantly improved the effect of SI increasing the number of tumour free mice at 110 weeks of age from 13% (SI) to 58% (BI). Both the number and the volume of tumour masses were reduced in BI than in SI groups. The protective effect of BI was associated with increased antibody production with isotype switching to IgG2a, augmented CD4 T cells, and increased in vivo cytotoxicity of HER-2/neu specific cytotoxic T lymphocytes, mainly in ECD1.5 and ECD3 groups. The transfer of sera from ECD1.5 mice to untreated HER-2/neu mice highly protected against tumour development than sera from SI mice. We conclude that BI induce a protective immunity effective over life span.
- Published
- 2017
46. Supplementation with tocotrienols from Bixa orellana improves the in vivo efficacy of daptomycin against methicillin-resistant Staphylococcus aureus in a mouse model of infected wound
- Author
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Oriana Simonetti, Mauro Provinciali, Oscar Cirioni, Andrea Giacometti, Elisa Pierpaoli, and Fiorenza Orlando
- Subjects
0301 basic medicine ,Methicillin-Resistant Staphylococcus aureus ,medicine.drug_class ,medicine.medical_treatment ,030106 microbiology ,Antibiotics ,Pharmaceutical Science ,Microbial Sensitivity Tests ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Adjuvants, Immunologic ,Daptomycin ,In vivo ,Drug Discovery ,Medicine ,Animals ,030212 general & internal medicine ,Pharmacology ,Mice, Inbred BALB C ,business.industry ,Vitamin E ,Tocotrienols ,Bixaceae ,Staphylococcal Infections ,Methicillin-resistant Staphylococcus aureus ,Anti-Bacterial Agents ,Disease Models, Animal ,Complementary and alternative medicine ,Staphylococcus aureus ,Wound Infection ,Molecular Medicine ,business ,Wound healing ,medicine.drug - Abstract
Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of skin and soft-tissue infection worldwide. An adequate immune response acts as a first line of defence against infections and therefore plays an essential role in the maintenance of health. Tocotrienols (T3s), the lesser known isomers of vitamin E, possess many biological properties and have been recognized as immunomodulators. Purpose The aim of this study was to investigate whether the in vivo supplementation with a mixture of 87.1% δ- and 12.9% γ-T3s extract from seeds of Bixa orellana, (T3s) could be effective in increasing the effect of daptomycin (DAP) in a mouse model of wound infection due to MRSA. Study design/methods Bacteria were inoculated onto full-thickness wound on the dorsal side of BALB/c mice at 5 × 106 CFU per mouse. Mice were randomized into five groups: an uninfected group, an infected-untreated group, a T3s-pretreated group with no antibiotics given after challenge, a T3s-pretreated group plus DAP given after challenge, a group only given DAP after challenge. Main outcome measures were: bacterial load on the wounds, analysis of Natural Killer (NK) cytotoxicity, immunological phenotype and markers of tissue repair. Results Our results showed that bacterial load in wounds from mice receiving T3s or DAP alone was 1- or 3-log10 lower, respectively, compared with the infected-untreated group. T3s plus daptomycin showed the highest efficacy, achieving a 4-log10 decrease in bacterial load. This higher antimicrobial effect was associated with increased levels of NK cytotoxicity and markers of wound repair. Conclusion These data suggest that treatment with T3s may be useful for the management of infected wounds as immune adjuvants in combination with DAP.
- Published
- 2017
47. In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria
- Author
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Carmela Silvestri, Oriana Simonetti, Andrea Giacometti, Elżbieta Kamysz, Susanna Mazzocato, Annamaria Offidani, Mauro Provinciali, Wojciech Kamysz, Fiorenza Orlando, Mario Guerrieri, Roberto Ghiselli, and Oscar Cirioni
- Subjects
Acinetobacter baumannii ,Imipenem ,Gram-negative bacteria ,Physiology ,medicine.drug_class ,Administration, Topical ,Antibiotics ,Microbial Sensitivity Tests ,medicine.disease_cause ,Biochemistry ,Microbiology ,Cellular and Molecular Neuroscience ,Endocrinology ,In vivo ,Escherichia coli ,polycyclic compounds ,medicine ,Animals ,Humans ,Mice, Inbred BALB C ,biology ,Colistin ,Pseudomonas aeruginosa ,Pseudomonas ,biology.organism_classification ,Anti-Bacterial Agents ,Disease Models, Animal ,Klebsiella pneumoniae ,Drug Therapy, Combination ,Gram-Negative Bacterial Infections ,Injections, Intraperitoneal ,Antimicrobial Cationic Peptides ,medicine.drug - Abstract
The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections.
- Published
- 2014
48. Correction for: LAV-BPIFB4 associates with reduced frailty in humans and its transfer prevents frailty progression in old mice
- Author
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Anna Maciag, Mauro Provinciali, Antonio D'Amato, Giuseppe Passarino, Fiorenza Orlando, Francesco Villa, Annibale Alessandro Puca, Elena Ciaglia, Marco Malavolta, Francesco De Rango, Paolo Madeddu, Andrea Basso, Serena Dato, Albino Carrizzo, Anna Ferrario, Carmine Vecchione, Giuseppina Rose, and Francesca Iannone
- Subjects
Oncology ,Aging ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,Cell Biology ,business - Published
- 2019
49. Effect of annatto-tocotrienols supplementation on the development of mammary tumors in HER-2/neu transgenic mice
- Author
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Elisa Pierpaoli, Mauro Provinciali, Francesco Galli, Alessandra Barucca, Valentina Viola, and Fiorenza Orlando
- Subjects
Cancer Research ,Receptor, ErbB-2 ,medicine.medical_treatment ,Apoptosis ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Mice ,Tissue Distribution ,Breast ,Cellular Senescence ,chemistry.chemical_classification ,Mammary tumor ,Tocotrienols ,Food Coloring Agents ,General Medicine ,Gene Expression Regulation, Neoplastic ,Female ,Cell aging ,Genetically modified mouse ,medicine.medical_specialty ,Breast Neoplasms ,Mammary Neoplasms, Animal ,Mice, Transgenic ,Adenocarcinoma ,Biology ,Chemoprevention ,In vivo ,Physiology (medical) ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,RNA, Messenger ,Cell Proliferation ,Reactive oxygen species ,Plant Extracts ,Cell growth ,Vitamin E ,Bixaceae ,Mammary Neoplasms, Experimental ,Carotenoids ,Oxidative Stress ,Endocrinology ,chemistry ,Dietary Supplements ,Cancer research ,Reactive Oxygen Species ,Oxidative stress - Abstract
Tocotrienols (T3), the lesser known isomers of vitamin E, have been reported to possess anticancer activity both in in vitro and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of dietary supplementation with annatto-T3 (90% δ-T3 and 10% γ-T3) on the spontaneous development of mammary tumors in HER-2/neu transgenic mice. Underlying mechanisms of the antitumor effect were evaluated by studying apoptosis, senescent-like growth arrest, immune modulation, oxidative effect and the expression of HER-2/neu in tumoral mammary glands of transgenic mice and in vitro in human and mice tumor cell lines. Annatto-T3 supplementation delayed the development of mammary tumors, reducing the number and size of mammary tumor masses and those of lung metastases. In annatto-T3-supplemented mice, both apoptosis and senescent-like growth arrest of tumor cells were increased in mammary glands while no immune modulation was observed. In vitro, a dose-dependent inhibition of cell growth, increased apoptosis and senescent-like growth arrest and a time-dependent accumulation of reactive oxygen species were observed in tumor cells treated with annatto-T3 or purified δ-T3. Annatto-T3 reduced both HER-2/neu mRNA and p185(HER-2/neu) protein in tumors and in tumor cell lines. The results show that the antitumor effect of annatto-T3 supplementation in HER-2/neu transgenic mice is mainly related to the direct induction of oxidative stress, senescent-like growth arrest and apoptosis of tumor cells rather than to an immune modulation.
- Published
- 2013
50. Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound
- Author
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Mauro Provinciali, Annamaria Offidani, Erika Fornasari, Oriana Simonetti, Leonardo Baldassarre, Antonio Di Stefano, Ivana Cacciatore, Andrea Giacometti, Fiorenza Orlando, Elena Orsetti, Elisa Pierpaoli, Oscar Cirioni, and Guendalina Lucarini
- Subjects
0301 basic medicine ,Physiology ,Staphylococcus ,lcsh:Medicine ,Minocycline ,Tigecycline ,medicine.disease_cause ,Biochemistry ,Mice ,Microbial Physiology ,lcsh:Science ,Pathology and laboratory medicine ,Multidisciplinary ,Pharmaceutics ,Granulation tissue ,Quorum Sensing ,Animal Models ,Medical microbiology ,Staphylococcal Infections ,Anti-Bacterial Agents ,medicine.anatomical_structure ,Staphylococcus aureus ,Connective Tissue ,Pathogens ,Anatomy ,Oligopeptides ,Subcutaneous tissue ,medicine.drug ,Research Article ,Methicillin-Resistant Staphylococcus aureus ,030106 microbiology ,Mouse Models ,Biology ,Staphylococcal infections ,Research and Analysis Methods ,Microbiology ,03 medical and health sciences ,Model Organisms ,Drug Therapy ,In vivo ,Tissue Repair ,medicine ,Animals ,Humans ,Animal Models of Disease ,Medicine and health sciences ,Wound Healing ,Biology and life sciences ,Bacteria ,lcsh:R ,Organisms ,Proteins ,medicine.disease ,Methicillin-resistant Staphylococcus aureus ,Microbial pathogens ,Animal Models of Infection ,Disease Models, Animal ,030104 developmental biology ,Biological Tissue ,Animal Studies ,Granulation Tissue ,Wound Infection ,lcsh:Q ,Bacterial pathogens ,Wound healing ,Physiological Processes ,Collagens - Abstract
In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x107 CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models.
- Published
- 2016
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