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  • 1
    Online Resource
    Online Resource
    Evaluation of Glycosylated PTGS2 in Colorectal Cancer for NSAIDS-Based Adjuvant Therapy
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 3 ( 2020-03-11), p. 683-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 3 ( 2020-03-11), p. 683-
    Abstract: Observational/retrospective studies indicate that prostaglandin-endoperoxide synthase-2 (PTGS2) inhibitors could positively affect colorectal cancer (CRC) patients’ survival after diagnosis. To obtain an acceptable cost/benefit balance, the inclusion of PTGS2 inhibitors in the adjuvant setting needs a selective criterion. We quantified the 72 kDa, CRC-associated, glycosylated form of PTGS2 in 100 frozen CRC specimens and evaluated PTGS2 localization by IHC in the same tumors, scoring tumor epithelial-derived and stroma-derived fractions. We also investigated the involvement of interleukin-1 beta (IL1β) in PTGS2 induction, both in vitro and in CRC lysates. Finally, we used overall survival (OS) as a criterion for patient selection. Glycosylated PTGS2 can be quantified with high sensibility in tissue lysates, but the expression in both tumor and stromal cells limits its use for predictive purposes. Immunohistochemistry (IHC) analysis indicates that stromal PTGS2 expression could exert a protective role on patient OS. Stromal PTGS2 was prevalently expressed by cancer-associated fibroblasts exerting a barrier function near the gut lumen, and it apparently favored the antitumor M1 macrophage population. IL1β was directly linked to gPTGS2 expression both in vitro and in tumors, but its activity was apparently prevalent on the stromal cell population. We suggest that stromal PTGS2 could exert a positive effect on patients OS when expressed in the luminal area of the tumor.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9030683
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 2
    Online Resource
    Online Resource
    A Case of Life-Threatening Bleeding Due to a Locally Advanced Breast Carcinoma Successfully Treated with Transcatheter Arterial Embolization
    MDPI AG ; 2023
    In:  Current Oncology Vol. 30, No. 2 ( 2023-02-09), p. 2187-2193
    Details
    In: Current Oncology, MDPI AG, Vol. 30, No. 2 ( 2023-02-09), p. 2187-2193
    Abstract: Locally advanced breast cancer (LABC) may rarely present with acute severe bleeding. A case report dealing with transcatheter arterial embolization to control acute bleeding in a patient with a voluminous ulcerated breast mass is described. Our findings confirm that the endovascular approach is effective in such patients in order to stabilize the patient whenever conventional treatments have failed or bleeding may be life-threatening.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    URL: Article
    DOI: 10.3390/curroncol30020169
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2270777-3
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  • 3
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    Online Resource
    Urinary Extracellular Vesicles and Salt-Losing Tubulopathies: A Proteomic Approach
    MDPI AG ; 2020
    In:  Proteomes Vol. 8, No. 2 ( 2020-05-09), p. 9-
    Details
    In: Proteomes, MDPI AG, Vol. 8, No. 2 ( 2020-05-09), p. 9-
    Abstract: Renal tubular cells release urinary extracellular vesicles (uEV) that are considered a promising source of molecular markers for renal dysfunction and injury. We investigated uEV proteomes of patients with hereditary salt-losing tubulopathies (SLTs), focusing on those caused by Gitelman and Bartter (BS) syndromes, to provide potential markers for differential diagnosis. Second morning urine was collected from patients with genetically proven SLTs and uEV were isolated by the ultracentrifugation-based protocol. The uEV proteome was run through a diagonal bidimensional electrophoresis (16BAC/SDS-PAGE), to improve hydrophobic protein resolution. Sixteen differential spots from the proteome of two variants (BS2 and BS3) were analysed by nLC-ESI-MS/MS after in-gel tryptic digestion. A total of 167 protein species were identified from 7 BS2 spots and 9 BS3 spot. Most of these proteins were membrane-associated proteins, in particular transmembrane proteins, and were related to typical renal functions. The differential content of some uEV was then validated by immunoblotting. Our work suggests that uEV proteomics represents a promising strategy for the identification of differential SLT proteins. This could play a role in understanding the pathophysiological disease mechanisms and may support the recognition of different syndromes.
    Type of Medium: Online Resource
    ISSN: 2227-7382
    URL: Article
    DOI: 10.3390/proteomes8020009
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720995-7
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  • 4
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    Online Resource
    Urinary Extracellular Vesicle Protein Profiles Discriminate Different Clinical Subgroups of Children with Idiopathic Nephrotic Syndrome
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 3 ( 2021-03-06), p. 456-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 3 ( 2021-03-06), p. 456-
    Abstract: Idiopathic nephrotic syndrome (INS) is the most frequent primary glomerular disease in children, displaying high grade proteinuria and oedema. The mainstay of therapy are steroids, and patients are usually classified according to the treatment response (sensitive vs. resistant). The mechanisms involved in INS pathogenesis and treatment responsiveness have not yet been identified. In this context, the analysis of urinary extracellular vesicles (UEv) is interesting, since they represent a molecular snapshot of the parental cells, offering a “fingerprint” for monitoring their status. Therefore, the aim of this study is to verify the feasibility of using UEv of INS patients as indicators of therapy response and its prediction. UEv were isolated from the urine of pediatric patients in remission after therapy; they showed characteristic electrophoresis profiles that matched specific patient subgroups. We then built a statistical model to interpret objectively each patient UEv protein profile: in particular, steroid-resistant patients cluster together with a very distinct pattern from other INS patients and controls. In conclusion, the evaluation of the UEv protein profile looks promising in the investigation of INS, showing a disease signature that might predict clinical evolution.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11030456
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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  • 5
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    Online Resource
    The Role of Polybrominated Diphenyl Ethers in Thyroid Carcinogenesis: Is It a Weak Hypothesis or a Hidden Reality? From Facts to New Perspectives
    MDPI AG ; 2018
    In:  International Journal of Environmental Research and Public Health Vol. 15, No. 9 ( 2018-08-24), p. 1834-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 15, No. 9 ( 2018-08-24), p. 1834-
    Abstract: In the last decades, the incidence of thyroid cancer has increased faster than that of any other malignant tumor type. The cause of thyroid cancer is likely multifactorial and a variety of both exogenous and endogenous has been identified as potential risk factors. Polybrominated diphenyl ethers (PBDEs), used since the 1970s as flame retardants, are still widespread and persistent pollutants today, although their production was definitely phased out in the western countries several years ago. Polybrominated diphenyl ethers are known endocrine disruptors, and the endocrine system is their primary target. Whereas animal studies have ascertained the ability of PBDEs to affect the normal functionality of the thyroid, evidence in humans remains inconclusive, and only a few epidemiological studies investigated the association between exposure to PBDEs and thyroid cancer. However, a number of clues suggest that a prolonged exposure to these chemicals might act a trigger of the most common malignancy of the endocrine system, whereas further studies with an advanced design are suggested.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph15091834
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2175195-X
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  • 6
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    Online Resource
    New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 21 ( 2020-10-24), p. 7787-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 21 ( 2020-10-24), p. 7787-
    Abstract: In recent years, the presence in the environment of chemical compounds with thyroid-disrupting effects is progressively increased. This phenomenon has risen concern for human health as the preservation of thyroid system homeostasis is essential for fetal development and for maintaining psychological and physiological wellbeing. An increasing number of studies explored the role of different classes of toxicants in the occurrence and severity of thyroid diseases, but large epidemiological studies are limited and only a few animal or in vitro studies have attempted to identify the mechanisms of chemical action. Recently, epigenetic changes such as alteration of methylation status or modification of non-coding RNAs have been suggested as correlated to possible deleterious effects leading to different thyroid disorders in susceptible individuals. This review aims to analyze the epigenetic alterations putatively induced by chemical exposures and involved in the onset of frequent thyroid diseases such as thyroid cancer, autoimmune thyroiditis and disruption of fetal thyroid homeostasis.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17217787
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 7
    Online Resource
    Online Resource
    Role of miR-133/Dio3 Axis in the T3-Dependent Modulation of Cardiac mitoK-ATP Expression
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 12 ( 2022-06-11), p. 6549-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 12 ( 2022-06-11), p. 6549-
    Abstract: The opening of the ATP-sensitive mitochondrial potassium channel (mitok-ATP) is a common goal of cardioprotective strategies in the setting of acute and chronic myocardial disease. The biologically active thyroid hormone (TH), 3-5-3-triiodothyronine (T3), has been indicated as a potential activator of mitoK-ATP but the underlying mechanisms are still elusive. Here we describe a novel role of T3 in the transcriptional regulation of mitoK and mitoSur, the recently identified molecular constituents of the channel. To mimic human ischemic heart damage, we used a rat model of a low T3 state as the outcome of a myocardial ischemia/reperfusion event, and neonatal rat cardiomyocytes (NRCM) challenged with hypoxia or H2O2. Either in the in vivo or in vitro models, T3 administration to recover the physiological concentrations was able to restore the expression level of both the channel subunits, which were found to be downregulated under the stress conditions. Furthermore, the T3-mediated transcriptional activation of mitoK-ATP in the myocardium and NRCM was associated with the repression of the TH-inactivating enzyme, deiodinase 3 (Dio3), and an up-regulation of the T3-responsive miR-133a-3p. Mechanistically, the loss and gain of function experiments and reporter gene assays performed in NRCM, have revealed a new regulatory axis whereby the silencing of Dio3 under the control of miR-133a-3p drives the T3-dependent modulation of cardiac mitoK and mitoSur transcription.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23126549
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
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    Online Resource
    Editorial for Special Issue: “MicroRNA in Cardiac Health and Disease”
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 24 ( 2022-12-08), p. 15567-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 24 ( 2022-12-08), p. 15567-
    Abstract: MicroRNAs (miRNAs) are endogenous, evolutionarily conserved, non-coding RNA molecules that influence most, if not all biological events, with cardiovascular development and homeostasis being no exceptions [...]
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232415567
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Online Resource
    T3 Critically Affects the Mhrt/Brg1 Axis to Regulate the Cardiac MHC Switch: Role of an Epigenetic Cross-Talk
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 10 ( 2020-09-24), p. 2155-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 10 ( 2020-09-24), p. 2155-
    Abstract: The LncRNA my-heart (Mhrt) and the chromatin remodeler Brg1 inhibit each other to respectively prevent or favor the maladaptive α-myosin-heavy-chain (Myh6) to β-myosin-heavy-chain (Myh7) switch, so their balance crucially guides the outcome of cardiac remodeling under stress conditions. Even though triiodothyronine (T3) has long been recognized as a critical regulator of the cardiac Myh isoform composition, its role as a modulator of the Mhrt/Brg1 axis is still unexplored. Here the effect of T3 on the Mhrt/Brg1 regulatory circuit has been analyzed in relation with chromatin remodeling and previously identified T3-dependent miRNAs. The expression levels of Mhrt, Brg1 and Myh6/Myh7 have been assessed in rat models of hyperthyroidism or acute myocardial ischemia/reperfusion (IR) treated with T3 replacement therapy. To gain mechanistic insights, in silico analyses and site-directed mutagenesis have been adopted in combination with gene reporter assays and loss or gain of function strategies in cultured cardiomyocytes. Our results indicate a pivotal role of Mhrt over-expression in the T3-dependent regulation of Myh switch. Mechanistically, T3 activates the Mhrt promoter at two putative thyroid hormone responsive elements (TRE) located in a crucial region that is necessary for both Mhrt activation and Brg1-dependent Mhrt repression. This newly identified T3 mode of action requires DNA chromatinization and is critically involved in mitigating the repressive function of the Brg1 protein on Mhrt promoter. In addition, T3 is also able to prevent the Brg1 over-expression observed in the post-IR setting through a pathway that might entail the T3-mediated up-regulation of miR-208a. Taken together, our data evidence a novel T3-responsive network of cross-talking epigenetic factors that dictates the cardiac Myh composition and could be of great translational relevance.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9102155
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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