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  • 11
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    In Vitro Evaluation of Postbiotics Produced from Bacterial Isolates Obtained from Rainbow Trout and Nile Tilapia against the Pathogens Yersinia ruckeri and Aeromonas salmonicida subsp. salmonicida
    MDPI AG ; 2023
    In:  Foods Vol. 12, No. 4 ( 2023-02-17), p. 861-
    Details
    In: Foods, MDPI AG, Vol. 12, No. 4 ( 2023-02-17), p. 861-
    Abstract: The use of antibiotics in aquaculture leads to the proliferation of multidrug-resistant bacteria, and an urgent need for developing new alternatives to prevent and control disease has, thus, arisen. In this scenario, postbiotics represent a promising tool to achieve this purpose; thus, in this study, isolation and selection of bacteria to further produce and evaluate their postbiotics antibacterial activity against fish pathogens was executed. In this respect, bacterial isolates from rainbow trout and Nile tilapia were obtained and tested in vitro against Yersinia ruckeri and Aeromonas salmonicida subsp. salmonicida. From 369 obtained isolates, 69 were selected after initial evaluation. Afterwards, additional screening was carried out by spot-on-lawn assay to finally select twelve isolates; four were identified as Pediococcus acidilactici, seven as Weissella cibaria, and one as Weissella paramesenteroides by matrix assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS). Selected bacteria were used to obtain postbiotic products to test their antagonistic activity through coculture challenge and broth microdilution assays. The influence of incubation time prior to postbiotic production on antagonistic behavior was also recorded. Two isolates identified as W. cibaria were able to significantly reduce (p 〈 0.05) A. salmonicida subsp. salmonicida’s growth in the coculture challenge up to 4.49 ± 0.05 Log CFU/mL, and even though the reduction in Y. ruckeri was not as effective, some inhibition on the pathogen’s growth was reported; at the same time, most of the postbiotic products obtained showed more antibacterial activity when obtained from broth cultures incubated for 72 h. Based on the results obtained, the preliminary identification of the isolates that expressed the highest inhibitory activity was confirmed by partial sequencing as W. cibaria. Through our study, it can be concluded that postbiotics produced by these strains are useful to inhibit the growth of the pathogens and could, thereby, be applicable in further research to develop suitable tools as feed additives for disease control and prevention in aquaculture.
    Type of Medium: Online Resource
    ISSN: 2304-8158
    URL: Article
    DOI: 10.3390/foods12040861
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704223-6
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  • 12
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    Cocrystals of Isoniazid with Polyphenols: Mechanochemical Synthesis and Molecular Structure
    MDPI AG ; 2020
    In:  Crystals Vol. 10, No. 7 ( 2020-07-02), p. 569-
    Details
    In: Crystals, MDPI AG, Vol. 10, No. 7 ( 2020-07-02), p. 569-
    Abstract: Isoniazid is used as anti-tuberculosis drug which possesses functional groups capable of forming hydrogen bonds. A series of cocrystals of isoniazid (INH) with polyphenolic coformers such as catechol (CAT), orcinol (ORC), 2-methylresorcinol (MER), pyrogallol (PYR), and phloroglucinol (PLG) were prepared by solvent-assisted grinding. Powder cocrystals were characterized by infrared (IR) spectroscopy and X-ray powder diffraction. The crystal structure of the cocrystals revealed the unexpected hydration of the INH-MER cocrystal and the preference of the (phenol) O–H∙∙∙N (pyridine) and (terminal) N-H∙∙∙O (phenol) heterosynthons in the stabilization of the structures. The supramolecular architecture of the cocrystals is affected by the conformation and the substitution pattern of the hydroxyl groups of the polyphenols.
    Type of Medium: Online Resource
    ISSN: 2073-4352
    URL: Article
    DOI: 10.3390/cryst10070569
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661516-2
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  • 13
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    The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study
    MDPI AG ; 2018
    In:  Journal of Clinical Medicine Vol. 7, No. 12 ( 2018-11-23), p. 473-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 7, No. 12 ( 2018-11-23), p. 473-
    Abstract: Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm7120473
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2662592-1
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  • 14
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    New Actors Driving the Epithelial–Mesenchymal Transition in Cancer: The Role of Leptin
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 12 ( 2020-12-15), p. 1676-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 12 ( 2020-12-15), p. 1676-
    Abstract: Leptin is a hormone secreted mainly by adipocytes; physiologically, it participates in the control of appetite and energy expenditure. However, it has also been linked to tumor progression in different epithelial cancers. In this review, we describe the effect of leptin on epithelial–mesenchymal transition (EMT) markers in different study models, including in vitro, in vivo, and patient studies and in various types of cancer, including breast, prostate, lung, and ovarian cancer. The different studies report that leptin promotes the expression of mesenchymal markers and a decrease in epithelial markers, in addition to promoting EMT-related processes such as cell migration and invasion and poor prognosis in patients with cancer. Finally, we report that leptin has the greatest biological relevance in EMT and tumor progression in breast, lung, prostate, esophageal, and ovarian cancer. This relationship could be due to the key role played by the enriched tumor microenvironment in adipose tissue. Together, these findings demonstrate that leptin is a key biomolecule that drives EMT and metastasis in cancer.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10121676
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 15
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    Increased 1,25(OH)2-Vitamin D Concentrations after Energy Restriction Are Associated with Changes in Skeletal Muscle Phenotype
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 2 ( 2021-02-12), p. 607-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 2 ( 2021-02-12), p. 607-
    Abstract: The influence of energy restriction (ER) on muscle is controversial, and the mechanisms are not well understood. To study the effect of ER on skeletal muscle phenotype and the influence of vitamin D, rats (n = 34) were fed a control diet or an ER diet. Muscle mass, muscle somatic index (MSI), fiber-type composition, fiber size, and metabolic activity were studied in tibialis cranialis (TC) and soleus (SOL) muscles. Plasma vitamin D metabolites and renal expression of enzymes involved in vitamin D metabolism were measured. In the ER group, muscle weight was unchanged in TC and decreased by 12% in SOL, but MSI increased in both muscles (p 〈 0.0001) by 55% and 36%, respectively. Histomorphometric studies showed 14% increase in the percentage of type IIA fibers and 13% reduction in type IIX fibers in TC of ER rats. Decreased size of type I fibers and reduced oxidative activity was identified in SOL of ER rats. An increase in plasma 1,25(OH)2-vitamin D (169.7 ± 6.8 vs. 85.4 ± 11.5 pg/mL, p 〈 0.0001) with kidney up-regulation of CYP27b1 and down-regulation of CYP24a1 was observed in ER rats. Plasma vitamin D correlated with MSI in both muscles (p 〈 0.001), with the percentages of type IIA and type IIX fibers in TC and with the oxidative profile in SOL. In conclusion, ER preserves skeletal muscle mass, improves contractile phenotype in phasic muscles (TC), and reduces energy expenditure in antigravity muscles (SOL). These beneficial effects are closely related to the increases in vitamin D secondary to ER.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13020607
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 16
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    Increasing Prevalence of HIV-1 Transmitted Drug Resistance in Portugal: Implications for First Line Treatment Recommendations
    MDPI AG ; 2020
    In:  Viruses Vol. 12, No. 11 ( 2020-10-30), p. 1238-
    Details
    In: Viruses, MDPI AG, Vol. 12, No. 11 ( 2020-10-30), p. 1238-
    Abstract: Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p 〈 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p 〈 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p 〈 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p 〈 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p 〈 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v12111238
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2516098-9
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  • 17
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    Caloric Intake in Renal Patients: Repercussions on Mineral Metabolism
    MDPI AG ; 2020
    In:  Nutrients Vol. 13, No. 1 ( 2020-12-23), p. 18-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 1 ( 2020-12-23), p. 18-
    Abstract: The aim of this paper is to review current knowledge about how calorie intake influences mineral metabolism focussing on four aspects of major interest for the renal patient: (a) phosphate (P) handling, (b) fibroblast growth factor 23 (FGF23) and calcitriol synthesis and secretion, (c) metabolic bone disease, and (d) vascular calcification (VC). Caloric intake has been shown to modulate P balance in experimental models: high caloric intake promotes P retention, while caloric restriction decreases plasma P concentrations. Synthesis and secretion of the phosphaturic hormone FGF23 is directly influenced by energy intake; a direct correlation between caloric intake and FGF23 plasma concentrations has been shown in animals and humans. Moreover, in vitro, energy availability has been demonstrated to regulate FGF23 synthesis through mechanisms in which the molecular target of rapamycin (mTOR) signalling pathway is involved. Plasma calcitriol concentrations are inversely proportional to caloric intake due to modulation by FGF23 of the enzymes implicated in vitamin D metabolism. The effect of caloric intake on bone is controversial. High caloric intake has been reported to increase bone mass, but the associated changes in adipokines and cytokines may as well be deleterious for bone. Low caloric intake tends to reduce bone mass but also may provide indirect (through modulation of inflammation and insulin regulation) beneficial effects on bone. Finally, while VC has been shown to be exacerbated by diets with high caloric content, the opposite has not been demonstrated with low calorie intake. In conclusion, although prospective studies in humans are needed, when planning caloric intake for a renal patient, it is important to take into consideration the associated changes in mineral metabolism.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13010018
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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  • 18
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    Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 8 ( 2023-04-10), p. 1125-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 8 ( 2023-04-10), p. 1125-
    Abstract: Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12081125
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 19
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    Continuous-Flow Hydrogenation of Methyl Levulinate Promoted by Zr-Based Mesoporous Materials
    MDPI AG ; 2019
    In:  Catalysts Vol. 9, No. 2 ( 2019-02-02), p. 142-
    Details
    In: Catalysts, MDPI AG, Vol. 9, No. 2 ( 2019-02-02), p. 142-
    Abstract: Several Zr-based materials, including ZrO2 and Zr-SBA-15, with different silicon/zirconium molar ratios, and ZrO2/Si-SBA-15 (where SBA-15 stands for Santa Barbara Amorphous material no. 15), have been prepared as hydrogenation catalysts. The materials were characterized using different characterization techniques including X-ray diffraction (XRD), N2 porosimetry, scanning electron microscopy (SEM/EDX), diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) of pyridine adsorption and the pulsed chromatographic method using pyridine and 2,6-dimethylpyridine as probe molecules, mainly, have been employed for the characterization of the structural, textural, and acidic properties of the synthesized materials, respectively. The catalysts have been evaluated in the hydrogenation reaction of methyl levulinate using 2-propanol as hydrogen donor solvent. The reaction conditions were investigated and stablished at 30 bar system pressure with a reaction temperature of 200 °C using around 0.1 g of catalyst and a flow rate of 0.2 mL/min flow rate of a 0.3 M methyl levulinate solution in 2-propanol. All catalysts employed in this work exhibited good catalytic activities under the investigated conditions, with conversion values in the 15–89% range and, especially, selectivity to Υ-valerolactone in the range of 76–100% (after one hour time on stream). The highest methyl levulinate conversion and selectivity was achieved by ZrO2/Si-SBA-15 which can be explained by the higher dispersion of ZrO2 particles together with a highest accessibility of the Zr sites as compared with other materials such as Zr-SBA-15, also investigated in this work.
    Type of Medium: Online Resource
    ISSN: 2073-4344
    URL: Article
    DOI: 10.3390/catal9020142
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662126-5
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  • 20
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    Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017
    MDPI AG ; 2020
    In:  Viruses Vol. 12, No. 3 ( 2020-02-28), p. 268-
    Details
    In: Viruses, MDPI AG, Vol. 12, No. 3 ( 2020-02-28), p. 268-
    Abstract: Migration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v12030268
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2516098-9
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