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71.
Teodolinda Di Risi Mariella Cuomo Roberta Vinciguerra Sara Ferraro Rosa Della Monica Davide Costabile Michela Buonaiuto Federica Trio Ettore Capoluongo Roberta Visconti Eleonora Riccio Antonio Pisani Lorenzo Chiariotti 《International journal of molecular sciences》2022,23(20)
Anderson–Fabry disease (FD) is an X-linked disease caused by a functional deficit of the α-galactosidase A enzyme. FD diagnosis relies on the clinical manifestations and research of GLA gene mutations. However, because of the lack of a clear genotype/phenotype correlation, FD diagnosis can be challenging. Recently, several studies have highlighted the importance of investigating DNA methylation patterns for confirming the correct diagnosis of different rare Mendelian diseases, but to date, no such studies have been reported for FD. Thus, in the present investigation, we analyzed for the first time the genome-wide methylation profile of a well-characterized cohort of patients with Fabry disease. We profiled the methylation status of about 850,000 CpG sites in 5 FD patients, all carrying the same mutation in the GLA gene (exon 6 c.901C>G) and presenting comparable low levels of α-Gal A activity. We found that, although the whole methylome profile did not discriminate the FD group from the unaffected one, several genes were significantly differentially methylated in Fabry patients. Thus, we provide here a proof of concept, to be tested in patients with different mutations and in a larger cohort, that the methylation state of specific genes can potentially identify Fabry patients and possibly predict organ involvement and disease evolution. 相似文献
72.
Eleonora A. Braga Marina V. Fridman Alexey M. Burdennyy Elena A. Filippova Vitaly I. Loginov Irina V. Pronina Alexey A. Dmitriev Nikolay E. Kushlinskii 《International journal of molecular sciences》2022,23(21)
A decrease in the miR-124 expression was observed in various epithelial cancers. Like a classical suppressor, miR-124 can inhibit the translation of multiple oncogenic proteins. Epigenetic mechanisms play a significant role in the regulation of miR-124 expression and involve hypermethylation of the MIR-124-1/-2/-3 genes and the effects of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) according to the model of competing endogenous RNAs (ceRNAs). More than 40 interactomes (lncRNA/miR-124/mRNA) based on competition between lncRNAs and mRNAs for miR-124 binding have been identified in various epithelial cancers. LncRNAs MALAT1, NEAT1, HOXA11-AS, and XIST are the most represented in these axes. Fourteen axes (e.g., SND1-IT1/miR-124/COL4A1) are involved in EMT and/or metastasis. Moreover, eight axes (e.g., OIP5-AS1/miR-124-5p/IDH2) are involved in key pathways, such as Wnt/b-catenin, E2F1, TGF-β, SMAD, ERK/MAPK, HIF-1α, Notch, PI3K/Akt signaling, and cancer cell stemness. Additionally, 15 axes impaired patient survival and three axes reduced chemo- or radiosensitivity. To date, 14 cases of miR-124 regulation by circRNAs have been identified. Half of them involve circHIPK3, which belongs to the exonic ecircRNAs and stimulates cell proliferation, EMT, autophagy, angiogenesis, and multidrug resistance. Thus, miR-124 and its interacting partners may be considered promising targets for cancer therapy. 相似文献
73.
Salvatore Ulisse Enke Baldini Daniele Pironi Federica Gagliardi Domenico Tripodi Augusto Lauro Sabino Carbotta Danilo Tarroni Matteo DArmiento Aldo Morrone Flavio Forte Flaminia Frattaroli Severino Persechino Teresa Odorisio Vito DAndrea Eleonora Lori Salvatore Sorrenti 《International journal of molecular sciences》2022,23(17)
Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic–pituitary–thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients. 相似文献
74.
75.
Maria Antonietta Grignano Stefania Bruno Simona Viglio Maria Antonietta Avanzini Marta Tapparo Marina Ramus Stefania Croce Chiara Valsecchi Eleonora Francesca Pattonieri Gabriele Ceccarelli Federica Manzoni Annalia Asti Carmelo Libetta Vincenzo Sepe Paolo Iadarola Marilena Gregorini Teresa Rampino 《International journal of molecular sciences》2022,23(18)
We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system. 相似文献
76.
Dr. Silvia Fallarini Irene P. Bhela Dr. Silvio Aprile Dr. Enza Torre Alice Ranza Elena Orecchini Dr. Eleonora Panfili Dr. Maria T. Pallotta Prof. Alberto Massarotti Dr. Marta Serafini Prof. Tracey Pirali 《ChemMedChem》2021,16(22):3439-3450
Inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) are considered a promising strategy in cancer immunotherapy as they are able to boost the immune response and to work in synergy with other immunotherapeutic agents. Despite the fact that no IDO1 inhibitor has been approved so far, recent studies have shed light on the additional roles that IDO1 mediates beyond its catalytic activity, conferring new life to the field. Here we present a novel class of compounds originated from a structure-based virtual screening made on IDO1 active site. The starting hit compound is a novel chemotype based on a [1,2,4]triazolo[4,3-a]pyridine scaffold, so far underexploited among the heme binding moieties. Thanks to the rational and in silico-guided design of analogues, an improvement of the potency to sub-micromolar levels has been achieved, with excellent in vitro metabolic stability and exquisite selectivity with respect to other heme-containing enzymes. 相似文献
77.
I Millot JP Daures D Bessaoud B Ledésert D Nebbia 《Canadian Metallurgical Quarterly》1997,45(6):483-492
BACKGROUND: Unbiased and reliable data are presently required for health planning concerning end stage renal diseases (ESRD) in Languedoc-Roussillon region of France. METHODS: A comprehensive retrospective study has been carried out on patients with ESRD in 1994 in this area. Information was collected from medical and social documents by physicians. The present report describes the management of patients and their demographic and epidemiologic characteristics. Multiple correspondence analysis was carried out to estimate to what extent mode of renal replacement therapy is determined by patient characteristics. RESULTS: An incidence of 11.4 for new cases of renal replacement therapy was found per 100,000 inhabitants. This represents an increase of 4.8% in the total number of patients. The patients were found to be elderly (25% being over 72 years) and to present with multiple pathologies (32.5% severe cardiac pathology; 20.7% arteritis of the lower limbs; 15.1% diabetes; 11.2% manifesting malignant tumors). Only 57.5% received dialysis within a hospital setting; 30.1% received dialysis at home; 13% perform autodialysis; 1.2% were being trained for home dialysis in December. The renal transplantation rate was 5.5%. No significant relationship was found between choice of therapy and age, renal disease, comorbidities and place of dwelling. CONCLUSIONS: This study demonstrates the great variety in the modes of treatment used, the facilities provided and the evolutive trend, which together make programming planning difficult. 相似文献
78.
Arjeh B. Galun Eleonora Shaubi Arie Markus Sarina Grinberg Jacob Zabicky 《Journal of the American Oil Chemists' Society》1984,61(1):102-103
Jojoba wax solutions were irradiated at wavelengths longer than 366 nm, in the presence of sensitizers, at room temperature.Cis-trans isomerization took place only with sensitizers with triplet energy greater than 68 kcal/mol. Quantum yields were low and
a conversion of up to 25% of thetrans isomer was achieved at the photostationary state. 相似文献
79.
Eleonora Balducci Lorella Ceschini Alessandro Morri Andrea Morri 《Journal of Materials Engineering and Performance》2017,26(8):3802-3812
This study aims to evaluate the effects of prolonged thermal exposure on both microstructural evolution and mechanical properties of the EN AW-4032 T6 piston alloy. For the purpose, the experimental activities have been carried out on samples machined from forged and heat-treated automotive pistons. The effects of overaging have been investigated in the temperature range of 140-290 °C, firstly by evaluating the time-temperature-hardness curves and then by carrying out room-temperature tensile tests on overaged samples. The material softening was substantial and extremely rapid when the soaking temperature exceeded 250 °C. During overaging, both the tensile strength and the residual hardness considerably decreased, and a relationship between these parameters has been established. The alloy behavior in the plastic field has been modeled according to the Hollomon’s equation, showing that both the strain hardening exponent and the strength coefficient are a function of the residual hardness. The results were finally related to the corresponding microstructural changes: OM and FEG-SEM metallographic and fractographic analyses on overaged samples gave evidence of coarsened precipitates along the grain boundaries. 相似文献
80.
Paola Indovina Eleonora Marcelli Francesca Pentimalli Piero Tanganelli Giulio Tarro Antonio Giordano 《Mass spectrometry reviews》2013,32(2):129-142
Lung cancer is the leading cause of cancer death in men and women in Western nations, and is among the deadliest cancers with a 5‐year survival rate of 15%. The high mortality caused by lung cancer is attributable to a late‐stage diagnosis and the lack of effective treatments. So, it is crucial to identify new biomarkers that could function not only to detect lung cancer at an early stage but also to shed light on the molecular mechanisms that underlie cancer development and serve as the basis for the development of novel therapeutic strategies. Considering that DNA‐based biomarkers for lung cancer showed inadequate sensitivity, specificity, and reproducibility, proteomics could represent a better tool for the identification of useful biomarkers and therapeutic targets for this cancer type. Among the proteomics technologies, the most powerful tool is mass spectrometry. In this review, we describe studies that use mass spectrometry‐based proteomics technologies to analyze tumor proteins and peptides, which might represent new diagnostic, prognostic, and predictive markers for lung cancer. We focus in particular on those findings that hold promise to impact significantly on the clinical management of this disease. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:129–142, 2013 相似文献