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  • 1
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 7 ( 2022-03-26), p. 3629-
    Abstract: The CD33 gene encodes for a member of the sialic-acid-binding immunoglobulin-type lectin (Siglec) family, and is one of the top-ranked Alzheimer’s disease (AD) risk genes identified by genome-wide association studies (GWAS). Many CD33 polymorphisms are associated with an increased risk of AD, but the function and potential mechanism of many CD33 single-nucleotide polymorphisms (SNPs) in promoting AD have yet to be elucidated. We recently identified the CD33 SNP rs2455069-A 〉 G (R69G) in a familial form of dementia. Here, we demonstrate an association between the G allele of the rs2455069 gene variant and the presence of AD in a cohort of 195 patients from southern Italy. We carried out in silico analysis of the 3D structures of CD33 carrying the identified SNP to provide insights into its functional effect. Structural models of the CD33 variant carrying the R69G amino acid change were compared to the CD33 wild type, and used for the docking analysis using sialic acid as the ligand. Our analysis demonstrated that the CD33-R69G variant may bind sialic acid at additional binding sites compared to the wild type, thus potentially increasing its affinity/specificity for this molecule. Our results led to a new hypothesis of rs2455069-A 〉 G SNP as a risk factor for AD, suggesting that a long-term cumulative effect of the CD33-R69G variant results from the binding of sialic acid, acting as an enhancer of the CD33 inhibitory effects on amyloid plaque degradation.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 7 ( 2019-03-28), p. 1548-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 7 ( 2019-03-28), p. 1548-
    Abstract: EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications. Here we describe the identification of a splicing isoform for the human EGR1 gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 6 ( 2022-05-30), p. 1167-
    Abstract: During an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as Fusarium spp. and yeasts, such as Candida spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species. Fusarium oxysporum is responsible for approximately 20% of human fusariosis, while Candida albicans is responsible for superficial mucosal and dermal infections and for disseminated bloodstream infections with a mortality rate above 40%. This study aims to investigate the interactions between C. albicans and F. oxysporum dual-species biofilm, considering variable formation conditions. Further, the ability of the WMR peptide, a modified version of myxinidin, to eradicate the mixed biofilm when used alone or in combination with fluconazole (FLC) was tested, and the efficacy of the combination of WMR and FLC at low doses was assessed, as well as its effect on the expression of some biofilm-related adhesin and hyphal regulatory genes. Finally, in order to confirm our findings in vivo and explore the synergistic effect of the two drugs, we utilized the Galleria mellonella infection model. We concluded that C. albicans negatively affects F. oxysporum growth in mixed biofilms. Combinatorial treatment by WMR and FLC significantly reduced the biomass and viability of both species in mature mixed biofilms, and these effects coincided with the reduced expression of biofilm-related genes in both fungi. Our results were confirmed in vivo since the synergistic antifungal activity of WMR and FLC increased the survival of infected larvae and reduced tissue invasion. These findings highlight the importance of drug combinations as an alternative treatment for C. albicans and F. oxysporum mixed biofilms.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 4
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 23 ( 2021-11-24), p. 12335-
    Abstract: Adolescent idiopathic scoliosis (AIS) has an incidence of 2–3% in the general population and a multifactorial etiology. The present study aims to analyze modifiable risk factors and their interactions in the development of AIS in order to increase knowledge about the disease and to prevent the evolution of AIS in young students with tailored public health strategies. A cross-sectional study was conducted over two consecutive school years among students attending 11 first-grade secondary schools in the province of Palermo, Italy. A self-administered questionnaire that investigated socio-demographical, physical and anamnestic characteristics and habits, focusing on possible risk factors associated with idiopathic scoliosis, was administered. In addition, a clinical evaluation was performed with Adams’ test and Bunnel’s inclinometer. Suspected AIS cases were associated with the practice of high-risk sports (p 〈 0.05), weekly physical activity lasting ≥3 h (p 〈 0.05), lower back pain (p 〈 0.001), posture disorders (p 〈 0.01) and having had no contact with a physician (p 〈 0.01). Practice of high-risk sports (adj OR = 1.83; CI 95% 1.11–4.76) and suffering of posture disorders (adj OR = 1.67; CI 95% 1.12–3.60) showed a significant association with a confirmed diagnosis of AIS (Cobb angle ≥ 10° at X-ray). The risk factors associated with AIS are still unclear. Therefore, it is crucial to identify early modifiable and multiple risk factors to prevent the evolution of scoliosis in school-age children.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
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  • 5
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 15 ( 2020-07-25), p. 5362-
    Abstract: In recent years, vaccination coverage rates against Human Papilloma Virus (HPV) in Europe have shown a decreasing trend and remain below the required standard. The present study aims to assess knowledge and attitudes regarding HPV infection and vaccination among a representative sample of preadolescents of Palermo, Italy. A survey was carried out throughout two questionnaires, before and after carrying out an educational intervention scheduled during school hours. A total of 1702 students attending first-grade secondary schools of the province of Palermo were enrolled (response rate 68.9%). Students attending third classes (adj OR = 1.18; CI 95% 1.03–1.36), being of higher socioeconomic status (adj OR = 1.35; CI 95% 1.05–1.73), who had previously received information about sexually transmitted diseases (STDs) at home (adj OR = 1.62; CI 95% 1.27–2.07) or at school (adj OR = 2.15; CI 95% 1.70–2.71) and who had ever heard in the past about HPV (adj OR = 1.80; CI 95% 1.42–2.29) showed a significantly higher baseline level of knowledge regarding HPV. Willingness to receive HPV vaccination, in a 10-point Likert scale, significantly increased between the pre- (8.51; SD ± 1.79) and post- (9.01 SD ± 1.52) intervention questionnaires (p 〈 0.001). A total of 188 out of 272 (69.1%) preadolescents attending five out eighteen schools involved in the project, who had not previously received the HPV vaccine, were vaccinated. During past years, education campaigns on HPV were mainly dedicated to adult women, excluding teenagers and omitting young males. It should therefore be of primary importance that school-based education and vaccination programmes be standardized.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2020
    In:  Non-Coding RNA Vol. 6, No. 4 ( 2020-11-12), p. 46-
    In: Non-Coding RNA, MDPI AG, Vol. 6, No. 4 ( 2020-11-12), p. 46-
    Abstract: Immediate early genes play an essential role in cellular responses to different stimuli. Many of them are transcription factors that regulate the secondary response gene expression. Non-coding RNAs may also be involved in this regulatory cascade. In fact, they are emerging as key actors of gene expression regulation, and evidence suggests that their dysregulation may underly pathological states. We previously took a snapshot of both coding and long non-coding RNAs differentially expressed in neuronal cells after brain-derived neurotrophic factor stimulation. Among these, the transcription factor EGR1 (a well-known immediate early gene) and LINC00473 (a primate-specific long non-coding RNA) that has emerged as an interesting RNA candidate involved in neuronal function and in cancer. In this work, we demonstrated that LINC00473 gene expression kinetics resembled that of immediate early genes in SH-SY5Y and HEK293T cells under different cell stimulation conditions. Moreover, we showed that the expression of LINC00473 is under the control of the transcription factor EGR1, providing evidence for an interesting functional relationship in neuron function.
    Type of Medium: Online Resource
    ISSN: 2311-553X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2813993-8
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