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  • 1
    Online Resource
    Online Resource
    High Instantaneous Inhibitory Potential of Bictegravir and the New Spiro-β-Lactam BSS-730A for HIV-2 Isolates from RAL-Naïve and RAL-Failing Patients
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 22 ( 2022-11-18), p. 14300-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 22 ( 2022-11-18), p. 14300-
    Abstract: Integrase inhibitors (INIs) are an important class of drugs for treating HIV-2 infection, given the limited number of drugs active against this virus. While the clinical efficacy of raltegravir and dolutegravir is well established, the clinical efficacy of bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of bictegravir against HIV-2 isolates from patients failing raltegravir-based therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from raltegravir-naïve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-β-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined integrase mutations E92A and Q148K conferred high-level resistance to raltegravir, and E92Q and T97A conferred resistance to raltegravir and dolutegravir. The antiviral activity of bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong antiviral synergism with raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of bictegravir and BSS-730A for raltegravir-naïve and raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2 infection. Overall, the results are consistent with the high clinical efficacy of raltegravir and dolutegravir for HIV-2 infection and suggest a promising clinical profile for bictegravir and BSS-730A.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232214300
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
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    A Prime-Boost Immunization Strategy with Vaccinia Virus Expressing Novel gp120 Envelope Glycoprotein from a CRF02_AG Isolate Elicits Cross-Clade Tier 2 HIV-1 Neutralizing Antibodies
    MDPI AG ; 2020
    In:  Vaccines Vol. 8, No. 2 ( 2020-04-07), p. 171-
    Details
    In: Vaccines, MDPI AG, Vol. 8, No. 2 ( 2020-04-07), p. 171-
    Abstract: Development of new immunogens eliciting broadly neutralizing antibodies (bNAbs) is a main priority for the HIV-1 vaccine field. Envelope glycoproteins from non-B-non-C HIV-1clades have not been fully explored as components of a vaccine. We produced Vaccinia viruses expressing a truncated version of gp120 (gp120t) from HIV-1 clades CRF02_AG, H, J, B, and C and examined their immunogenicity in mice and rabbits. Mice primed with the recombinant Vaccinia viruses and boosted with the homologous gp120t or C2V3C3 polypeptides developed antibodies that bind potently to homologous and heterologous envelope glycoproteins. Notably, a subset of mice immunized with the CRF02_AG-based envelope immunogens developed a cross-reactive neutralizing response against tier 2 HIV-1 Env-pseudoviruses and primary isolates. Rabbits vaccinated with the CRF02_AG-based envelope immunogens also generated potent binding antibodies, and one animal elicited antibodies that neutralized almost all (13 of 16, 81.3%) tier 2 HIV-1 isolates tested. Overall, the results suggest that the novel CRF02_AG-based envelope immunogens and prime-boost immunization strategy elicit the type of immune responses required for a preventive HIV-1 vaccine.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines8020171
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2703319-3
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  • 3
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    An HIV-1/HIV-2 Chimeric Envelope Glycoprotein Generates Binding and Neutralising Antibodies against HIV-1 and HIV-2 Isolates
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 10 ( 2023-05-22), p. 9077-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 10 ( 2023-05-22), p. 9077-
    Abstract: The development of immunogens that elicit broadly reactive neutralising antibodies (bNAbs) is the highest priority for an HIV vaccine. We have shown that a prime-boost vaccination strategy with vaccinia virus expressing the envelope glycoprotein gp120 of HIV-2 and a polypeptide comprising the envelope regions C2, V3 and C3 elicits bNAbs against HIV-2. We hypothesised that a chimeric envelope gp120 containing the C2, V3 and C3 regions of HIV-2 and the remaining parts of HIV-1 would elicit a neutralising response against HIV-1 and HIV-2. This chimeric envelope was synthesised and expressed in vaccinia virus. Balb/c mice primed with the recombinant vaccinia virus and boosted with an HIV-2 C2V3C3 polypeptide or monomeric gp120 from a CRF01_AG HIV-1 isolate produced antibodies that neutralised 〉 60% (serum dilution 1:40) of a primary HIV-2 isolate. Four out of nine mice also produced antibodies that neutralised at least one HIV-1 isolate. Neutralising epitope specificity was assessed using a panel of HIV-1 TRO.11 pseudoviruses with key neutralising epitopes disrupted by alanine substitution (N160A in V2; N278A in the CD4 binding site region; N332A in the high mannose patch). The neutralisation of the mutant pseudoviruses was reduced or abolished in one mouse, suggesting that neutralising antibodies target the three major neutralising epitopes in the HIV-1 envelope gp120. These results provide proof of concept for chimeric HIV-1/HIV-2 envelope glycoproteins as vaccine immunogens that can direct the antibody response against neutralising epitopes in the HIV-1 and HIV-2 surface glycoproteins.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24109077
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
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    Online Resource
    Pharyngeal Airspace Alterations after Using the Mandibular Advancement Device in the Treatment of Obstructive Sleep Apnea Syndrome
    MDPI AG ; 2022
    In:  Life Vol. 12, No. 6 ( 2022-06-02), p. 835-
    Details
    In: Life, MDPI AG, Vol. 12, No. 6 ( 2022-06-02), p. 835-
    Abstract: Background: Mandibular Advancement Devices (MADs), inserted in non-surgical treatments for obstructive sleep apnea and hypopnea syndrome (OSAHS), are used intra-orally during the sleep period, with the aim of promoting mandibular protrusion. The aim of the study is to analyze the changes in the upper airway after the use of an MAD in the treatment of OSAHS. Methods: 60 patients diagnosed with OSAHS, as established by the Sleep Medicine Service, underwent treatment with the Silensor SL device at the Stomatology Service of the University Hospital Center of Coimbra, from January 2018 to January 2019. All patients completed two polysomnographies and two lateral teleradiographies: one before starting treatment (T0) and one after 1 year of treatment (T1). In the lateral teleradiography performed after one year of treatment, the patient had the MAD placed intra-orally. The linear measurements of the airspace proposed by the Arnett/Gunson FAB Surgery cephalometric analysis were measured at four craniometric points: A, MCI, B, Pog. Results: The results demonstrate an anteroposterior airway enlargement in two of the four points studied with the MAD placed intra-orally (B and Pog point). The greatest average increase is observed at point Pog (3 mm), followed by B (1 mm), and finally, point A (0.6 mm). Conclusions: This study proved that there is an improvement in anteroposterior measurements at various points in the upper airways after treatment with MAD.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life12060835
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662250-6
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  • 5
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    The Role of Temperament in Mediating the Association between Adolescence Dating Violence and Early Traumatic Experiences
    MDPI AG ; 2022
    In:  Youth Vol. 2, No. 3 ( 2022-07-27), p. 285-294
    Details
    In: Youth, MDPI AG, Vol. 2, No. 3 ( 2022-07-27), p. 285-294
    Abstract: Violence in adolescent intimate relationships poses a real threat to adolescent well-being and is a risk factor for recurrent violent patterns in adult marital relationships. The present study aimed to understand the relationship between different dimensions of childhood trauma and dating violence perpetration and the mediating role of temperament. The sample was composed of 3497 adolescents (n = 1549 boys, n = 1948 girls; M = 1.56, SD = 0.497) aged between 10 and 22 years (M = 15.15, SD = 1.83). Instruments used in this study included the Social Desirability Scale, the Childhood Trauma Questionnaire (CTQ), and the Early Adolescent Temperament Questionnaire (EATQ). The results show that temperament plays a mediating role in the relationship between dating violence perpetration and emotional, physical, and sexual abuse. Furthermore, the results suggest that adolescents who have been abused in childhood tend to demonstrate more temperamental problems and a greater susceptibility to the perpetration of teen dating violence, but only in the more severe dimensions of childhood trauma.
    Type of Medium: Online Resource
    ISSN: 2673-995X
    URL: Article
    DOI: 10.3390/youth2030021
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 3099310-6
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  • 6
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    Online Resource
    One Step Nucleic Acid Amplification (OSNA) Lysate Samples Are Suitable to Establish a Transcriptional Metastatic Signature in Patients with Early Stage Hormone Receptors-Positive Breast Cancer
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 23 ( 2022-11-28), p. 5855-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 23 ( 2022-11-28), p. 5855-
    Abstract: The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel lymph nodes (SLNs) staging in breast cancer (BC). As major disadvantage, OSNA precludes prognostic information based on structural evaluation of SLNs. Our aim is to identify biomarkers related to tumor-microenvironment interplay exploring gene expression data from the OSNA remaining lysate. This study included 32 patients with early stage hormone receptors-positive BC. Remaining OSNA lysates were prepared for targeted RNA-sequencing analysis. Identification of differentially expressed genes (DEGs) was performed by DESeq2 in R and data analysis in STATA. The results show that, in metastatic SLNs, several genes were upregulated: KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC, NECTIN2, LRG1, CD276, FOXM1 and IGF1R. Hierarchical clustering analysis revealed three different clusters. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. The overexpression of the immune suppressive genes VTCN1 and CD276 may explain that no direct evidence of activation of immune response in metastatic SLNs was found. We show that OSNA results may be improved incorporating microenvironment-related biomarkers that may be useful in the future for prognosis stratification and immunotherapy selection. As OSNA assay is being implemented for SLNs staging in other cancers, this approach could also have a wider utility.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14235855
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 7
    Online Resource
    Online Resource
    Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China
    MDPI AG ; 2016
    In:  Toxins Vol. 8, No. 5 ( 2016-05-05), p. 142-
    Details
    In: Toxins, MDPI AG, Vol. 8, No. 5 ( 2016-05-05), p. 142-
    Type of Medium: Online Resource
    ISSN: 2072-6651
    URL: Article
    DOI: 10.3390/toxins8050142
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2518395-3
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  • 8
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    The Spatiotemporal Links between Urban and Rural Regions through the Sale and Consumption of Agri-Food Products
    MDPI AG ; 2023
    In:  Sustainability Vol. 15, No. 15 ( 2023-08-06), p. 12038-
    Details
    In: Sustainability, MDPI AG, Vol. 15, No. 15 ( 2023-08-06), p. 12038-
    Abstract: The asymmetries between rural and urban areas have continued to increase over the last decades, contributing to an imbalance of economic, social, and territorial dimensions between regions. Urban stores specialized in the commercialization of rural provenance agri-food products can have a role in the promotion of interrelations between the countryside and the cities and contribute to publicizing and promoting rural regions among the urban populations and tourists. Thus, this work aims to understand and characterize the growth of these stores in two of the main urban and tourist centers of Oporto and Lisbon. For this purpose, we developed an analytical framework with the support of a spatial analysis using geographic information systems (GIS) to understand their organization as well as the spatiotemporal evolution and distribution. We also investigated the geographical patterns of the supply chains of marketed agri-food products and the spatial relationships between agri-food products from their production to their commercialization and consumption. The results revealed that most of the agri-food products originate in the inland rural regions of the country with a clear geographical connection between the analyzed stores and specific territories. Moreover, we verify an increased interest and consumption of agri-food products and a spontaneous increase in this type of store. Overall, these stores, in addition to selling agri-food products, are also promoters of rural territories in an urban environment.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su151512038
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518383-7
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  • 9
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    Online Resource
    Effect of Quercetin on Mycorrhizal Synthesis between Tuberborchii and Arbutusunedo L. In Vitro Plants
    MDPI AG ; 2021
    In:  Microbiology Research Vol. 12, No. 1 ( 2021-02-23), p. 69-81
    Details
    In: Microbiology Research, MDPI AG, Vol. 12, No. 1 ( 2021-02-23), p. 69-81
    Abstract: Arbutus unedo L. is a Mediterranean species used for fruit production; it is tolerant to drought and shows regeneration ability following forest fires. Mycorrhizal plants with Tuber borchii add resilience and value. This study aims to test the effect of quercetin on mycorrhizal synthesis between T. borchii and A. unedo. Two genotypes selected for fruit production and hydric stress tolerance, were micropropagated for mycorrhizal synthesis, accomplished during ex vitro rooting in perlite, using lyophilized spores of T. borchii suspended in culture media with different quercetin levels (0–10 µM). Six months after inoculation, plants were transferred to pots and maintained in nursery. Ten and 12 months after inoculation, roots were morphological examined and molecularly characterized using ITS1-5.8SITS2 rDNA region and specific primers. Results showed that mycorrhizae establishment was dependent on studied factors (genotype, quercetin level, and culture medium) and their interaction (genotype X culture medium). Quercetin levels up to 2.0 µM favored mycorrhizae establishment and plant growth, although levels superior to 4 µM showed a toxic effect. Quercetin showed to be an efficient factor on inducing mycorrhiza thriving independent of the genotype. Morphological observations and molecular analysis confirmed the permanence of the fungus association 10 and 12 months after inoculation.
    Type of Medium: Online Resource
    ISSN: 2036-7481
    URL: Article
    DOI: 10.3390/microbiolres12010007
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2571057-6
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  • 10
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    Online Resource
    The Polar Lipidome of Cultured Emiliania huxleyi: A Source of Bioactive Lipids with Relevance for Biotechnological Applications
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 10 ( 2020-10-12), p. 1434-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 10 ( 2020-10-12), p. 1434-
    Abstract: Polar lipids from microalgae have aroused greater interest as a natural source of omega-3 (n-3) polyunsaturated fatty acids (PUFA), an alternative to fish, but also as bioactive compounds with multiple applications. The present study aims to characterize the polar lipid profile of cultured microalga Emiliania huxleyi using hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry (HILIC–MS) and fatty acids (FA) analysis by gas chromatography (GC–MS). The lipidome of E. huxleyi revealed the presence of distinct n-3 PUFA (40% of total FA), namely docosahexaenoic acid (22:6n-3) and stearidonic acid (18:4n-3), which give this microalga an increased commercial value as a source of n-3 PUFA present in the form of polar lipids. A total of 134 species of polar lipids were identified and some of these species, particularly glycolipids, have already been reported for their bioactive properties. Among betaine lipids, the diacylglyceryl carboxyhydroxymethylcholine (DGCC) class is the least reported in microalgae. For the first time, monomethylphosphatidylethanolamine (MMPE) has been found in the lipidome of E. huxleyi. Overall, this study highlights the potential of E. huxleyi as a sustainable source of high-value polar lipids that can be exploited for different applications, namely human and animal nutrition, cosmetics, and pharmaceuticals.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10101434
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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