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  • 1
    Online Resource
    Online Resource
    Neurosensory Alterations in Retinopathy of Prematurity: A Window to Neurological Impairments Associated to Preterm Birth
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 7 ( 2022-07-06), p. 1603-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 7 ( 2022-07-06), p. 1603-
    Abstract: Retinopathy of prematurity (ROP) is one of the main blinding diseases affecting preterm newborns and is classically considered a vascular disorder. The premature exposure to the extrauterine environment, which is hyperoxic in respect to the intrauterine environment, triggers a cascade of events leading to retinal ischemia which, in turn, makes the retina hypoxic thus setting off angiogenic processes. However, many children with a history of ROP show persistent vision impairment, and there is evidence of an association between ROP and neurosensory disabilities. This is not surprising given the strict relationship between neuronal function and an adequate blood supply. In the present work, we revised literature data evidencing to what extent ROP can be considered a neurodegenerative disease, also taking advantage from data obtained in preclinical models of ROP. The involvement of different retinal cell populations in triggering the neuronal damage in ROP was described along with the neurological outcomes associated to ROP. The situation of ROP in Italy was assessed as well.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10071603
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 2
    Online Resource
    Online Resource
    A Comprehensive Comparison of Bovine and Porcine Decellularized Pericardia: New Insights for Surgical Applications
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 3 ( 2020-02-28), p. 371-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 3 ( 2020-02-28), p. 371-
    Abstract: Xenogeneic pericardium-based substitutes are employed for several surgical indications after chemical shielding, limiting their biocompatibility and therapeutic durability. Adverse responses to these replacements might be prevented by tissue decellularization, ideally removing cells and preserving the original extracellular matrix (ECM). The aim of this study was to compare the mostly applied pericardia in clinics, i.e., bovine and porcine tissues, after their decellularization, and obtain new insights for their possible surgical use. Bovine and porcine pericardia were submitted to TRICOL decellularization, based on osmotic shock, detergents and nuclease treatment. TRICOL procedure resulted in being effective in cell removal and preservation of ECM architecture of both species’ scaffolds. Collagen and elastin were retained but glycosaminoglycans were reduced, significantly for bovine scaffolds. Tissue hydration was varied by decellularization, with a rise for bovine pericardia and a decrease for porcine ones. TRICOL significantly increased porcine pericardial thickness, while a non-significant reduction was observed for the bovine counterpart. The protein secondary structure and thermal denaturation profile of both species’ scaffolds were unaltered. Both pericardial tissues showed augmented biomechanical compliance after decellularization. The ECM bioactivity of bovine and porcine pericardia was unaffected by decellularization, sustaining viability and proliferation of human mesenchymal stem cells and endothelial cells. In conclusion, decellularized bovine and porcine pericardia demonstrate possessing the characteristics that are suitable for the creation of novel scaffolds for reconstruction or replacement: differences in water content, thickness and glycosaminoglycans might influence some of their biomechanical properties and, hence, their indication for surgical use.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10030371
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 3
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    Online Resource
    Similarities and Differences between Vestibular Migraine and Recurrent Vestibular Symptoms—Not Otherwise Specified (RVS-NOS)
    MDPI AG ; 2023
    In:  Audiology Research Vol. 13, No. 3 ( 2023-06-08), p. 466-472
    Details
    In: Audiology Research, MDPI AG, Vol. 13, No. 3 ( 2023-06-08), p. 466-472
    Abstract: Menière’s disease and vestibular migraine (VM) are two common inner ear disorders whose diagnoses are based on clinical history and audiometric exams. In some cases, patients have been reporting different episodes of vertigo for years but not fulfilling the Bárány Society criteria for either. These are called Recurrent Vestibular Symptoms—Not Otherwise Specified (RVS-NOS). It is still under debate if this is a single disease entity or a part of the spectrum of already established disorders. The purpose of our work was to establish similarities and differences with VM in terms of clinical history, bedside examination, and family history. We enrolled 28 patients with RVS-NOS who were followed for at least 3 years with stable diagnosis; results were compared with those of 34 subjects having a diagnosis of definite VM. The age of onset of vertigo was lower in VM than in RVS-NOS (31.2 vs. 38.4 years). As for the duration of attacks and symptoms, we detected no differences other than subjects with RVS-NOS reporting milder attacks. Cochlear accompanying symptoms were more frequently reported by VM subjects (one subject reporting tinnitus and another one reported tinnitus and fullness). Motion sickness was equally reported by subjects across two samples (around 50% for both). Bipositional long-lasting, non-paroxysmal nystagmus was the most common finding in the two groups, with no significant difference. Finally, the percentage of familial cases of migrainous headache and episodic vertigo did not differ between the two samples. In conclusion, RVS-NOS shares some common aspects with VM, including the temporal profile of attacks, motion sickness (commonly considered a migraine precursor), bedside examination, and family history. Our results are not inconsistent with the possibility that RVS-NOS may be a heterogeneous disorder, even if some of these subjects may share common pathophysiological mechanisms with VM.
    Type of Medium: Online Resource
    ISSN: 2039-4349
    URL: Article
    DOI: 10.3390/audiolres13030041
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2612981-4
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  • 4
    Online Resource
    Online Resource
    Tako-Tsubo Syndrome in Amyotrophic Lateral Sclerosis: Single-Center Case Series and Brief Literature Review
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 15 ( 2023-07-28), p. 12096-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 15 ( 2023-07-28), p. 12096-
    Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with variable phenotypic expressions which has been associated with autonomic dysfunction. The cardiovascular system seems to be affected especially in the context of bulbar involvement. We describe four new cases of Tako-Tsubo syndrome (TTS) in ALS patients with an appraisal of the literature. We present a late-stage ALS patient with prominent bulbar involvement that presented TTS during hospitalization. We then retrospectively identify three additional ALS–TTS cases reporting relevant clinical findings. TTS cardiomyopathy has been observed in different acute neurological conditions, and the co-occurrence of ALS and TTS has already been reported. Cardiovascular autonomic dysfunctions have been described in ALS, especially in the context of an advanced diseases and with bulbar involvement. Noradrenergic hyperfunction linked to sympathetic denervation and ventilatory deficits coupled in different instances with a trigger event could play a synergistic role in the development of TTS in ALS. Sympathetic hyperfunctioning and ventilatory deficits in conjunction with cardiac autonomic nerves impairment may play a role in the development of TTS in a context of ALS.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241512096
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Is There a Standard Adjuvant Therapy for Resected Pancreatic Cancer?
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 10 ( 2019-10-12), p. 1547-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 10 ( 2019-10-12), p. 1547-
    Abstract: Surgical resection remains the only treatment that offers a potential chance of long-term survival. Unfortunately, about 80% of patients treated with curative intent will develop recurrence. Since 2001, adjuvant therapy with gemcitabine or 5-fluorouracyle was recommended. This approach allows a median overall survival (OS) of around 23 months, and 5-year survival of 22%. In recent years, two phase-3 trials investigating new chemotherapy regimens resulted in considerably improved survival times. The doublet gemcitabine–capecitabine has shown improvement in OS from 25.5 to 28 months (p = 0.032) compared to gemcitabine, in the ESPAC-4 trial. Later, preliminary results of PRODIGE 24 trial presented at the 2018 ASCO meeting showed a superiority of a combination chemotherapy regimen with fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) when compared to gemcitabine alone, both in terms of median disease-free survival (21.6 vs. 12.8 months, p 〈 0.0001) and OS (54.4 vs. 35 months, p = 0.003). Contrary to chemotherapy, the role of adjuvant radiotherapy is still controversial, even in the case of R1 surgery. A randomized trial exploring the role of chemoradiotherapy in this setting is now ongoing in the US (RTOG-0848). Overall, the management of localized pancreatic adenocarcinoma is evolving. In this review, we summarize the current status and the most up-to-date developments in adjuvant treatment.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11101547
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 6
    Online Resource
    Online Resource
    Involvement of NINJ2 Protein in Inflammation and Blood–Brain Barrier Transmigration of Monocytes in Multiple Sclerosis
    MDPI AG ; 2022
    In:  Genes Vol. 13, No. 11 ( 2022-10-25), p. 1946-
    Details
    In: Genes, MDPI AG, Vol. 13, No. 11 ( 2022-10-25), p. 1946-
    Abstract: Multiple sclerosis (MS) is an inflammatory neurodegenerative disorder of the central nervous system (CNS). The migration of immune cells into the CNS is essential for its development, and plasma membrane molecules play an important role in triggering and maintaining the inflammation. We previously identified ninjurin2, a plasma membrane protein encoded by NINJ2 gene, as involved in the occurrence of relapse under Interferon-β treatment in MS patients. The aim of the present study was to investigate the involvement of NINJ2 in inflammatory conditions and in the migration of monocytes through the blood–brain barrier (BBB). We observed that NINJ2 is downregulated in monocytes and in THP-1 cells after stimulation with the pro-inflammatory cytokine LPS, while in hCMEC/D3 cells, which represent a surrogate of the BBB, LPS stimulation increases its expression. We set up a transmigration assay using an hCMEC/D3 transwell-based model, finding a higher transmigration rate of monocytes from MS subjects compared to healthy controls (HCs) in the case of an activated hCMEC/D3 monolayer. Moreover, a positive correlation between NINJ2 expression in monocytes and monocyte migration rate was observed. Overall, our results suggest that ninjurin2 could be involved in the transmigration of immune cells into the CNS in pro-inflammatory conditions. Further experiments are needed to elucidate the exact molecular mechanisms.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes13111946
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527218-4
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  • 7
    Online Resource
    Online Resource
    Improvement of Metastatic Colorectal Cancer Patient Survival: Single Institution Experience
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 3 ( 2019-03-15), p. 369-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 3 ( 2019-03-15), p. 369-
    Abstract: The survival rates of patients with metastatic colorectal cancer (mCRC) have improved in recent years. We analysed the survival of mCRC patients followed at a single institution over the last 17 years. We retrospectively collected data from 899 mCRC patients treated from 2001 to 2016. Patients were divided into two groups based on the year of diagnosis: Cohort A (2001–2006) and Cohort B (2007–2014). A total of 788 patients were analysed. The median survival of the whole population was 32.0 months with a significant difference between Cohort A and B (29.2 vs. 33.5 months; p = 0.041). Surgical procedures significantly increased in Cohort B, however, no significant changes in survival were observed in patients undergoing surgery (58.9 months Cohort A vs. 58.2 months Cohort B, p = 0.822). Similarly, we did not demonstrate survival improvement in patients treated with systemic therapy alone (18.9 months Cohort A vs. 20.7 months Cohort B; p = 0.948). At the multivariate analysis, right-sided primary and synchronous metastatic tumour were found to be independent unfavorable prognostic factors. Improvements of mCRC patient survival might relate to integrated approach, with more patients undergoing extra-hepatic surgery. The medical approach seems to have had a more favourable impact on subgroups characterized by a worse prognosis.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11030369
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Online Resource
    Assessment of a High Sensitivity Method for Identification of IDH1 R132x Mutations in Tumors and Plasma of Intrahepatic Cholangiocarcinoma Patients
    MDPI AG ; 2019
    In:  Cancers Vol. 11, No. 4 ( 2019-03-30), p. 454-
    Details
    In: Cancers, MDPI AG, Vol. 11, No. 4 ( 2019-03-30), p. 454-
    Abstract: Hotspot codon 132 mutations (R132xIDH1m) are frequent in intrahepatic cholangiocarcinoma (ICC), are druggable by anti-IDH1m agents, and could represent a marker of disease progression. Developing an assay to identify R132xIDH1m would provide a useful tool to select patients benefitting from targeted treatments. We tested a quantitative real-time allele-specific polymerase chain reaction (qPCR)-based method to detect the main R132xIDH1m in an Italian ICC series (n = 61) of formalin-fixed paraffin-embedded (FFPE) samples, and on circulating-free DNA samples. The outcomes were compared with nested PCR/Sanger sequencing. Reconstitution experiments of plasmids harboring the different R132xIDH1m mixed with wild-type (WT) DNA demonstrated that qPCR is able to detect at least 2% of all mutated allele. High efficiency was also observed on patient-derived mutated DNA mixed with WT DNA (up to 10% and 0.3 ng of mutated template); qPCR detected 16.4% of mutated samples (one R132G, three R132C and six R132L) while nested PCR/Sanger sequencing only 8.2% (four R132L and one R132G). In a single patient with an R132C-mutated tumor, qPCR was also performed on plasma samples collected at four time-points, observing an increase correlating with disease progression. In conclusion, we developed a qPCR assay which could represent a fast, inexpensive and sensitive tool both for detection of R132xIDH1m in ICC samples and monitoring disease progression from liquid biopsy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers11040454
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 9
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    Online Resource
    HIF-1-Dependent Induction of β3 Adrenoceptor: Evidence from the Mouse Retina
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 8 ( 2022-04-08), p. 1271-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 8 ( 2022-04-08), p. 1271-
    Abstract: A major player in the homeostatic response to hypoxia is the hypoxia-inducible factor (HIF)-1 that transactivates a number of genes involved in neovessel proliferation in response to low oxygen tension. In the retina, hypoxia overstimulates β-adrenoceptors (β-ARs) which play a key role in the formation of pathogenic blood vessels. Among β-ARs, β3-AR expression is increased in proliferating vessels in concomitance with increased levels of HIF-1α and vascular endothelial growth factor (VEGF). Whether, similarly to VEGF, hypoxia-induced β3-AR upregulation is driven by HIF-1 is still unknown. We used the mouse model of oxygen-induced retinopathy (OIR), an acknowledged model of retinal angiogenesis, to verify the hypothesis of β3-AR transcriptional regulation by HIF-1. Investigation of β3-AR regulation over OIR progression revealed that the expression profile of β3-AR depends on oxygen tension, similar to VEGF. The additional evidence that HIF-1α stabilization decouples β3-AR expression from oxygen levels further indicates that HIF-1 regulates the expression of the β3-AR gene in the retina. Bioinformatics predicted the presence of six HIF-1 binding sites (HBS #1-6) upstream and inside the mouse β3-AR gene. Among these, HBS #1 has been identified as the most suitable HBS for HIF-1 binding. Chromatin immunoprecipitation-qPCR demonstrated an effective binding of HIF-1 to HBS #1 indicating the existence of a physical interaction between HIF-1 and the β3-AR gene. The additional finding that β3-AR gene expression is concomitantly activated indicates the possibility that HIF-1 transactivates the β3-AR gene. Our results are indicative of β3-AR involvement in HIF-1-mediated response to hypoxia.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11081271
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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  • 10
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    The Heart–Brain Interplay in Multiple Sclerosis from Pathophysiology to Clinical Practice: A Narrative Review
    MDPI AG ; 2023
    In:  Journal of Cardiovascular Development and Disease Vol. 10, No. 4 ( 2023-04-01), p. 153-
    Details
    In: Journal of Cardiovascular Development and Disease, MDPI AG, Vol. 10, No. 4 ( 2023-04-01), p. 153-
    Abstract: Multiple sclerosis (MS) is a chronic neurological disorder characterized by inflammation in the central nervous system (CNS) that leads to neurodegeneration. The clinical course is highly variable, but its prevalence is rising worldwide, partly thanks to novel disease-modifying therapies. Additionally, the lifespan of people with MS is increasing, and for this reason, it is fundamental to have a multidisciplinary approach to MS. MS may be associated with cardiovascular diseases (CVD), but there is scarce attention on this issue. In particular, CNS is essential in regulating the autonomic system and heart activity. Moreover, cardiovascular risk factors show a higher prevalence in MS patients. On the other hand, conditions like Takotsubo syndrome are rare complications of MS. The parallelism between MS and myocarditis is also interesting. Finally, cardiac toxicity represents a not infrequent adverse reaction to MS drugs. This narrative review aims to provide an overview of cardiovascular complications in MS and their management to prompt further clinical and pre-clinical research on this topic.
    Type of Medium: Online Resource
    ISSN: 2308-3425
    URL: Article
    DOI: 10.3390/jcdd10040153
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2777082-5
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