Isabella Gigante  Valeria Tutino  Francesco Russo  Valentina De Nunzio  Sergio Coletta  Raffaele Armentano  Alberto Crovace  Maria Gabriella Caruso  Antonella Orlando  Maria Notarnicola 《International journal of molecular sciences》2021,22(6)

The administration of a ketogenic diet (KD) has been considered therapeutic in subjects with irritable bowel syndrome (IBS). This study aimed to investigate the molecular mechanisms by which a low-carbohydrate diet, such as KD, can improve gastrointestinal symptoms and functions in an animal model of IBS by evaluating possible changes in intestinal tissue expression of endocannabinoid receptors. In rats fed a KD, we detected a significant restoration of cell damage to the intestinal crypt base, a histological feature of IBS condition, and upregulation of CB1 and CB2 receptors. The diet also affected glucose metabolism and intestinal membrane permeability, with an overexpression of the glucose transporter GLUT1 and tight junction proteins in treated rats. The present data suggest that CB receptors represent one of the molecular pathways through which the KD works and support possible cannabinoid-mediated protection at the intestinal level in the IBS rats after dietary treatment.  相似文献   

    

Chiara Camponeschi  Maria De Carluccio  Susanna Amadio  Maria Elisabetta Clementi  Beatrice Sampaolese  Cinzia Volont  Maria Tredicine  Vincenzo Romano Spica  Rosa Di Liddo  Francesco Ria  Fabrizio Michetti  Gabriele Di Sante 《International journal of molecular sciences》2021,22(24)

S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.  相似文献   

    

Stefano Mastrangelo  Serena Rivetti  Silvia Triarico  Alberto Romano  Giorgio Attin  Palma Maurizi  Antonio Ruggiero 《International journal of molecular sciences》2021,22(23)

Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m² are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody–antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.  相似文献   

    

Nicola Caporaso  Alessandro Genovese  Maria Angeles Pérez-Jiménez  Raul Olivero-David  Raffaele Sacchi 《European Journal of Lipid Science and Technology》2021,123(9):2000350

The unique sensory characteristics of extra virgin olive oil (EVOO) depend upon its volatile composition. This work investigates the impact of olive fruit harvesting time and growing location on the volatile composition of the obtained EVOO, on four typical Spanish olive varieties (Cornicabra, Picual, Castellana, Manzanilla Cacereña). Several growing locations within the Madrid region (Spain) are studied to assess the natural variability attributed to the environmental factors. Aroma compounds are analyzed by solid-phase microextraction coupled with gas-chromatography and mass spectrometry, and sensory analysis. A considerable different behavior is observed depending on the olive variety and ripening stage. Statistically significant differences are obtained for volatile compounds biosynthesized from the lipoxygenase pathway and other fatty acid metabolism routes, which results in significant differences in their aroma profiles. Practical applications: These results have practical applicability for the olive oil industry and regulatory bodies. For example, for protected designation of origin EVOOs the aroma profile needs to be consistent over different production lots. The outcome of this research is of interest to the olive oil industry to get a better insight into the expected variability and interactions among cultivars, small pedoclimatic differences within the same broader area, and the harvesting date on the sensory and volatile profile of the resulting EVOO.  相似文献   

    

Stefania Stella  Michele Massimino  Livia Manzella  Maria Stella Pennisi  Elena Tirr  Chiara Romano  Silvia Rita Vitale  Adriana Puma  Cristina Tomarchio  Sandra Di Gregorio  Giuseppe Alberto Palumbo  Paolo Vigneri 《International journal of molecular sciences》2021,22(2)

Hypereosinophilia (HE) is a heterogeneous condition with a persistent elevated eosinophil count of >350/mm³, which is reported in various (inflammatory, allergic, infectious, or neoplastic) diseases with distinct pathophysiological pathways. HE may be associated with tissue or organ damage and, in this case, the disorder is classified as hypereosinophilic syndrome (HES). Different studies have allowed for the discovery of two major pathogenetic variants known as myeloid or lymphocytic HES. With the advent of molecular genetic analyses, such as T-cell receptor gene rearrangement assays and Next Generation Sequencing, it is possible to better characterize these syndromes and establish which patients will benefit from pharmacological targeted therapy. In this review, we highlight the molecular alterations that are involved in the pathogenesis of eosinophil disorders and revise possible therapeutic approaches, either implemented in clinical practice or currently under investigation in clinical trials.  相似文献   

    

Chiara Romano  Federica Martorana  Maria Stella Pennisi  Stefania Stella  Michele Massimino  Elena Tirr  Silvia Rita Vitale  Sandra Di Gregorio  Adriana Puma  Cristina Tomarchio  Livia Manzella 《International journal of molecular sciences》2021,22(14)

Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient’s diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.  相似文献   

    

Vincenza Ylenia Cusenza  Alessandra Bisagni  Monia Rinaldini  Chiara Cattani  Raffaele Frazzi 《International journal of molecular sciences》2021,22(9)

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Carolina Giordano  Giovanni Sabatino  Simona Romano  Giuseppe Maria Della Pepa  Martina Tufano  Quintino Giorgio D&#x;Alessandris  Simone Cottonaro  Marco Gessi  Mario Balducci  Maria Fiammetta Romano  Alessandro Olivi  Simona Gaudino  Cesare Colosimo 《International journal of molecular sciences》2021,22(7)

Magnetic resonance imaging (MRI) is the gold standard for glioblastoma (GBM) patient evaluation. Additional non-invasive diagnostic modalities are needed. GBM is heavily infiltrated with tumor-associated macrophages (TAMs) that can be found in peripheral blood. FKBP51s supports alternative-macrophage polarization. Herein, we assessed FKBP51s expression in circulating monocytes from 14 GBM patients. The M2 monocyte phenotype was investigated by qPCR and flow cytometry using antibodies against PD-L1, CD163, FKBP51s, and CD14. MRI assessed morphologic features of the tumors that were aligned to flow cytometry data. PD-L1 expression on circulating monocytes correlated with MRI tumor necrosis score. A wider expansion in circulating CD163/monocytes was measured. These monocytes resulted in a dramatic decrease in patients with an MRI diagnosis of complete but not partial surgical removal of the tumor. Importantly, in patients with residual tumor, most of the peripheral monocytes that in the preoperative stage were CD163/FKBP51s− had turned into CD163/FKBP51s+. After Stupp therapy, CD163/FKBP51s+ monocytes were almost absent in a case of pseudoprogression, while two patients with stable or true disease progression showed sustained levels in such circulating monocytes. Our work provides preliminary but meaningful and novel results that deserve to be confirmed in a larger patient cohort, in support of potential usefulness in GBM monitoring of CD163/FKBP51s/CD14 immunophenotype in adjunct to MRI.  相似文献   

    

Caterina Peggion  Maria Lina Massimino  Raphael Severino Bonadio  Federica Lia  Raffaele Lopreiato  Stefano Cagnin  Tito Calì  Alessandro Bertoli 《International journal of molecular sciences》2021,22(21)

Mitochondria–ER contacts (MERCs), tightly regulated by numerous tethering proteins that act as molecular and functional connections between the two organelles, are essential to maintain a variety of cellular functions. Such contacts are often compromised in the early stages of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). TDP-43, a nuclear protein mainly involved in RNA metabolism, has been repeatedly associated with ALS pathogenesis and other neurodegenerative diseases. Although TDP-43 neuropathological mechanisms are still unclear, the accumulation of the protein in cytoplasmic inclusions may underlie a protein loss-of-function effect. Accordingly, we investigated the impact of siRNA-mediated TDP-43 silencing on MERCs and the related cellular parameters in HeLa cells using GFP-based probes for MERCs quantification and aequorin-based probes for local Ca²⁺ measurements, combined with targeted protein and mRNA profiling. Our results demonstrated that TDP-43 down-regulation decreases MERCs density, thereby remarkably reducing mitochondria Ca²⁺ uptake after ER Ca²⁺ release. Thorough mRNA and protein analyses did not highlight altered expression of proteins involved in MERCs assembly or Ca²⁺-mediated ER–mitochondria cross-talk, nor alterations of mitochondrial density and morphology were observed by confocal microscopy. Further mechanistic inspections, however, suggested that the observed cellular alterations are correlated to increased expression/activity of GSK3β, previously associated with MERCs disruption.  相似文献   

    

Mario R. Romano  Fiammetta Catania  Filippo Confalonieri  Piero Zollet  Davide Allegrini  Jessica Sergenti  Francesco B. Lanza  Mariantonia Ferrara  Martina Angi 《International journal of molecular sciences》2021,22(18)

Toxic tumour syndrome (TTS) is a particularly aggressive form of secondary vasculopathy occurring after radiation therapy of uveal melanoma due to the persistence of the necrotic tumour mass inside the eye. The development of TTS confers a particularly unfavourable functional and anatomical ocular prognosis, ultimately requiring enucleation in most cases if untreated. Vitreoretinal (VR) surgery has been successfully applied for treatment and prevention of TTS using both resecting and non-resecting techniques. In this systematic review, we aim to define characteristics of uveal melanomas benefiting the most from secondary VR surgery and to outline the optimal type and timing of VR intervention in such cases. Analysis of the literature reveals that endoresection should be performed within 3 months after radiotherapy to tumours thicker than 7 mm and with a largest basal diameter between 8 mm and 15 mm with post-equatorial location, especially after proton beam treatment. Alternatively, endodrainage remains a valid therapeutic option in eyes with macula-off retinal detachment, tumour diameter larger than 15 mm or ciliary body involvement. VR surgery can be successful in the management of TTS following radiotherapy for uveal melanoma when timing and indication are appropriately evaluated.  相似文献