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  • 1
    Online Resource
    Online Resource
    Circulating Biomarkers of CDK4/6 Inhibitors Response in Hormone Receptor Positive and HER2 Negative Breast Cancer
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 11 ( 2021-05-27), p. 2640-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 11 ( 2021-05-27), p. 2640-
    Abstract: CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are the standard treatment for patients with hormone receptor-positive and HER2 negative (HR+/HER2−) metastatic breast cancer. Patients might show intrinsic and acquired resistance, which leads to treatment failure and progression. Circulating biomarkers have the potential advantages of recognizing patients who might not respond to treatment, monitoring treatment effects and identifying markers of acquired resistance during tumor progression with a simple withdrawal of peripheral blood. Genomic alterations on circulating tumor DNA and serum thymidine kinase activity, but also circulating tumor cells, epigenetic or exosome markers are currently being tested as markers of CDK4/6i treatment response, even though none of these have been integrated into clinical practice. In this review, we discuss the recent advancements in the development of circulating biomarkers of CDK4/6i response in patients with HR+/HER2−breast cancer.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13112640
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Epigenetics as an Evolutionary Tool for Centromere Flexibility
    MDPI AG ; 2020
    In:  Genes Vol. 11, No. 7 ( 2020-07-16), p. 809-
    Details
    In: Genes, MDPI AG, Vol. 11, No. 7 ( 2020-07-16), p. 809-
    Abstract: Centromeres are the complex structures responsible for the proper segregation of chromosomes during cell division. Structural or functional alterations of the centromere cause aneuploidies and other chromosomal aberrations that can induce cell death with consequences on health and survival of the organism as a whole. Because of their essential function in the cell, centromeres have evolved high flexibility and mechanisms of tolerance to preserve their function following stress, whether it is originating from within or outside the cell. Here, we review the main epigenetic mechanisms of centromeres’ adaptability to preserve their functional stability, with particular reference to neocentromeres and holocentromeres. The centromere position can shift in response to altered chromosome structures, but how and why neocentromeres appear in a given chromosome region are still open questions. Models of neocentromere formation developed during the last few years will be hereby discussed. Moreover, we will discuss the evolutionary significance of diffuse centromeres (holocentromeres) in organisms such as nematodes. Despite the differences in DNA sequences, protein composition and centromere size, all of these diverse centromere structures promote efficient chromosome segregation, balancing genome stability and adaptability, and ensuring faithful genome inheritance at each cellular generation.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes11070809
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527218-4
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  • 3
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    Online Resource
    Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 1 ( 2020-01-18), p. 264-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 1 ( 2020-01-18), p. 264-
    Abstract: Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9010264
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 4
    Online Resource
    Online Resource
    Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 14 ( 2023-07-21), p. 4813-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 14 ( 2023-07-21), p. 4813-
    Abstract: (1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017–2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index 〈 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients’ outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12144813
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 5
    Online Resource
    Online Resource
    How Can We Treat Vulvar Carcinoma in Pregnancy? A Systematic Review of the Literature
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 4 ( 2021-02-17), p. 836-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 4 ( 2021-02-17), p. 836-
    Abstract: According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17–41 years). The tumor size range was 0.3–15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5–48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13040836
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 6
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    Online Resource
    Drug Repurposing in Rare Diseases: An Integrative Study of Drug Screening and Transcriptomic Analysis in Nephropathic Cystinosis
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 23 ( 2021-11-27), p. 12829-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 23 ( 2021-11-27), p. 12829-
    Abstract: Diagnosis and cure for rare diseases represent a great challenge for the scientific community who often comes up against the complexity and heterogeneity of clinical picture associated to a high cost and time-consuming drug development processes. Here we show a drug repurposing strategy applied to nephropathic cystinosis, a rare inherited disorder belonging to the lysosomal storage diseases. This approach consists in combining mechanism-based and cell-based screenings, coupled with an affordable computational analysis, which could result very useful to predict therapeutic responses at both molecular and system levels. Then, we identified potential drugs and metabolic pathways relevant for the pathophysiology of nephropathic cystinosis by comparing gene-expression signature of drugs that share common mechanisms of action or that involve similar pathways with the disease gene-expression signature achieved with RNA-seq.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms222312829
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Online Resource
    Impact of a Programme for Water Affordability on Residential Consumption: Implementation of the “Programa Mínimo Vital de Agua Potable” in Bogotá, Colombia
    MDPI AG ; 2018
    In:  Water Vol. 10, No. 2 ( 2018-02-06), p. 158-
    Details
    In: Water, MDPI AG, Vol. 10, No. 2 ( 2018-02-06), p. 158-
    Abstract: Affordability of services is a determinant for people’s level of access to water. In this study, we analyse the effect of a programme aimed at improving the affordability of water services on users’ water consumption. The programme was implemented in 2012 by the local government of the city of Bogotá, Colombia, intending to provide an essential “lifeline” volume of water to poor households free of charge. Our assessment was carried out with secondary data and used difference-in-difference estimators in a panel data analysis of a two-period sample: 2011 and 2014. The unit of analysis was defined based on the city’s administrative divisions and the socio-economic stratification of residences. Over the period analysed, beneficiaries’ household consumption increased, reaching per capita consumption levels closer to those of the upper strata of users. Results suggest that the programme contributes to increased consumption and equity among users.
    Type of Medium: Online Resource
    ISSN: 2073-4441
    URL: Article
    DOI: 10.3390/w10020158
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2521238-2
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  • 8
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    Online Resource
    Chronic Intestinal Failure in Children: An International Multicenter Cross-Sectional Survey
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 9 ( 2022-04-30), p. 1889-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 9 ( 2022-04-30), p. 1889-
    Abstract: Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1–4 and 14–18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores 〈 −2. One-third had %IVSE/REE 〉 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14091889
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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  • 9
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    Online Resource
    Effectiveness of Combination of Tibolone and Lactobacilli Plus Lactoferrin in Postmenopausal Women with Vulvar Vestibular Pain: A Preliminary Report
    MDPI AG ; 2024
    In:  Nutrients Vol. 16, No. 14 ( 2024-07-22), p. 2378-
    Details
    In: Nutrients, MDPI AG, Vol. 16, No. 14 ( 2024-07-22), p. 2378-
    Abstract: Background: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy. Methods: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 109 CFU per capsule) in combination with bovine lactoferrin (Respecta®). Each product was taken once daily for 90 days. Results: After 90 d of therapy with TIB+ Respecta®, in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test. Conclusions: This study provides evidence that the combination of TIB+ Respecta® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu16142378
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
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  • 10
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    Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 5 ( 2021-05-01), p. 647-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 5 ( 2021-05-01), p. 647-
    Abstract: Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13050647
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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