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  • 1
    Online Resource
    Online Resource
    Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
    MDPI AG ; 2023
    In:  Pharmaceutics Vol. 15, No. 6 ( 2023-06-05), p. 1661-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 15, No. 6 ( 2023-06-05), p. 1661-
    Abstract: Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient’s response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics15061661
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Characterization of Resveratrol, Oxyresveratrol, Piceatannol and Roflumilast as Modulators of Phosphodiesterase Activity. Study of Yeast Lifespan
    MDPI AG ; 2020
    In:  Pharmaceuticals Vol. 13, No. 9 ( 2020-08-30), p. 225-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 13, No. 9 ( 2020-08-30), p. 225-
    Abstract: Our desire to live longer has led to an ever-increasing number of novel antiaging products. However, few molecules have any real effect and new ones need to be studied before they can be used commercially. In this contribution, activation of the caloric restriction (CR) pathway was studied using different three (resveratrol, oxyresveratrol and piceatannol)—a family with demonstrated bioactivity on phosphodiesterase activity. The high-affinity phosphodiesterase type 2 (PDE2) of Saccharomyces cerevisiae was expressed in Escherichia coli, purified and characterized. The activity and the inhibitory activity of each stilbene was studied, and the findings were compared in vitro and in silico with those obtained with roflumilast—a human PDE4 inhibitor widely used in chronic obstructive pulmonary diseases. Finally, an in vivo chronological lifespan assay using WT S. cerevisiae and ΔPDE2 S. cerevisiae strains was carried out. It was demonstrated that stilbenes can modulate yPDE2 activity, increasing the lifespan of the yeast by 18% over a control (in combination with other pathways). In addition, roflumilast increased the lifespan in the WT strain. The findings as a whole would increase the range of lifespan products available and suggest novel uses for approved drugs.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph13090225
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Interference of Meteorological Variables on Night Sky Observation in Rural and Urban Zones of South-Western Spain
    MDPI AG ; 2023
    In:  Sustainability Vol. 15, No. 14 ( 2023-07-11), p. 10887-
    Details
    In: Sustainability, MDPI AG, Vol. 15, No. 14 ( 2023-07-11), p. 10887-
    Abstract: Several factors affect the visibility of the night sky, most significantly artificial light at night (ALAN), meteorological conditions and Moon illumination. There are few studies that analyse the effect of meteorological conditions and Moon illumination, especially in rural areas (where the ALAN level is lower). An analysis of these variables could be relevant for sky observation, especially for astronomical observatories, usually located in rural areas with low ALAN. Knowledge of the relevant variables in the observation allows for the correct planning of the observation. The observer can consult meteorological agencies for forecasts of these variables, allowing him to know in advance whether the observation will be carried out under optimal conditions. In this study, a photometer and a weather station were installed in various municipalities located in rural areas of south-western Spain. This equipment was also installed in the city of Badajoz (urban area with high ALAN). These devices carried out simultaneous measurements of night sky darkness (NSB) and meteorological conditions for a period of approximately 6 months. A statistical analysis of the recorded data was carried out. Only the Moon illumination was slightly correlated with NSB in both cases (−0.3 in rural areas and −0.35 in urban areas). Sky temperature only proved a correlation with NSB in the urban area (−0.41). The correlations indicated are significant at the 0.01 level. The results obtained in the urban area were confirmed by a second analysis using meteorological data provided by a meteorological agency, obtaining similar results. A web application was developed that allows for real-time consultation of NSB and meteorological data for each area, which can help observe the starry sky. Globally, the results obtained in this study could help in the planning of stargazing in both urban and rural areas, allowing one to know in advance if weather conditions would affect the perception capacity.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su151410887
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518383-7
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  • 4
    Online Resource
    Online Resource
    Digital Pregnancy Test Powered by an Air-Breathing Paper-Based Microfluidic Fuel Cell Stack Using Human Urine as Fuel
    MDPI AG ; 2022
    In:  Sensors Vol. 22, No. 17 ( 2022-09-02), p. 6641-
    Details
    In: Sensors, MDPI AG, Vol. 22, No. 17 ( 2022-09-02), p. 6641-
    Abstract: The direct integration of paper-based microfluidic fuel cells (μFC’s) toward creating autonomous lateral flow assays has attracted attention. Here, we show that an air-breathing paper-based μFC could be used as a power supply in pregnancy tests by oxidizing the human urine used for the diagnosis. We present an air-breathing paper-based μFC connected to a pregnancy test, and for the first time, as far as we know, it is powered by human urine without needing any external electrolyte. It uses TiO2-Ni as anode and Pt/C as cathode; the performance shows a maximum value of voltage and current and power densities of ∼0.96 V, 1.00 mA cm−2, and 0.23 mW cm−2, respectively. Furthermore, we present a simple design of a paper-based μFC’s stack powered with urine that shows a maximum voltage and maximum current and power densities of ∼1.89 V, 2.77 mA cm−2 and 1.38 mW cm−2, respectively, which powers the display of a pregnancy test allowing to see the analysis results.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    URL: Article
    DOI: 10.3390/s22176641
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2052857-7
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  • 5
    Online Resource
    Online Resource
    Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 3 ( 2020-01-31), p. 964-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 3 ( 2020-01-31), p. 964-
    Abstract: Donation after circulatory death (DCD) could improve donor heart availability; however, warm ischemia-reperfusion injury raises concerns about graft quality. Mechanical postconditioning (MPC) may limit injury, but mechanisms remain incompletely characterized. Therefore, we investigated the roles of glucose metabolism and key signaling molecules in MPC using an isolated rat heart model of DCD. Hearts underwent 20 min perfusion, 30 min global ischemia, and 60 minu reperfusion with or without MPC (two cycles: 30 s reperfusion—30 s ischemia). Despite identical perfusion conditions, MPC either significantly decreased (low recovery = LoR; 32 ± 5%; p 〈 0.05), or increased (high recovery = HiR; 59 ± 7%; p 〈 0.05) the recovery of left ventricular work compared with no MPC (47 ± 9%). Glucose uptake and glycolysis were increased in HiR vs. LoR hearts (p 〈 0.05), but glucose oxidation was unchanged. Furthermore, in HiR vs. LoR hearts, phosphorylation of raptor, a downstream target of AMPK, increased (p 〈 0.05), cytochrome c release (p 〈 0.05) decreased, and TNFα content tended to decrease. Increased glucose uptake and glycolysis, lower mitochondrial damage, and a trend towards decreased pro-inflammatory cytokines occurred specifically in HiR vs. LoR MPC hearts, which may result from greater AMPK activation. Thus, we identify endogenous cellular mechanisms that occur specifically with cardioprotective MPC, which could be elicited in the development of effective reperfusion strategies for DCD cardiac grafts.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21030964
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Shall We Dance? Dancing Modulates Executive Functions and Spatial Memory
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 6 ( 2020-03-17), p. 1960-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 6 ( 2020-03-17), p. 1960-
    Abstract: Background: Aging is generally considered to be related to physical and cognitive decline. This is especially prominent in the frontal and parietal lobes, underlying executive functions and spatial memory, respectively. This process could be successfully mitigated in certain ways, such as through the practice of aerobic sports. With regard to this, dancing integrates physical exercise with music and involves retrieval of complex sequences of steps and movements creating choreographies. Methods: In this study, we compared 26 non-professional salsa dancers (mean age 55.3 years, age-range 49–70 years) with 20 non-dancers (mean age 57.6 years, age-range 49–70 years) by assessing two variables: their executive functions and spatial memory performance. Results: results showed that dancers scored better that non-dancers in our tests, outperforming controls in executive functions-related tasks. Groups did not differ in spatial memory performance. Conclusions: This work suggests that dancing can be a valid way of slowing down the natural age-related cognitive decline. A major limitation of this study is the lack of fitness assessment in both groups. In addition, since dancing combines multiple factors like social contact, aerobic exercise, cognitive work with rhythms, and music, it is difficult to determine the weight of each variable.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17061960
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 7
    Online Resource
    Online Resource
    A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers
    MDPI AG ; 2019
    In:  Polymers Vol. 11, No. 5 ( 2019-05-04), p. 801-
    Details
    In: Polymers, MDPI AG, Vol. 11, No. 5 ( 2019-05-04), p. 801-
    Abstract: Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization may improve treatment and, dismissing any adverse effects, its interaction with cyclodextrins (CDs) was studied. The Higuchi-Connors method was used to determine the complexation constant with different CDs, pH values and temperatures. Molecular docking was used to predict interaction between the complexes. An in vitro digestion experiment was carried out to test roflumilast protection. Finally, the photostability of the complex was evaluated. The complex formed with β-CD had the highest K11 value (646 ± 34 M−1), although this value decreased with increasing temperature. Similarly, K11 decreased as the pH increased. In vitro digestion showed that CDs protect the drug during digestion and even improve its bioaccessibility. Finally, CDs reduced the drug’s extreme photosensitivity, originating a fluorescence signal, which is described for first time. The kinetic parameters of the reaction were obtained. This study not only completes the complexation study of roflumilast-CD, but also points to the need to protect roflumilast from light, suggesting that tablets containing the drug might be reformulated.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym11050801
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527146-5
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  • 8
    Online Resource
    Online Resource
    Influence of Illumination Parameters on Night Sky Observation in Rural Areas
    MDPI AG ; 2023
    In:  Sustainability Vol. 15, No. 12 ( 2023-06-09), p. 9359-
    Details
    In: Sustainability, MDPI AG, Vol. 15, No. 12 ( 2023-06-09), p. 9359-
    Abstract: Currently, there are concerns about the significant increase in the level of night-time light pollution, which has become more dramatic in recent years. This causes several environmental problems and makes it impossible to observe the starry night sky, especially in rural areas where observatories are often located. Incorrect orientation and arrangement of lighting are often responsible for this pollution. This study quantified the level of interference of lighting parameters in the night sky. The influence of other environmental factors which may interfere with observation was also evaluated. A predictive model was developed to determine the level of darkness in rural areas. It was concluded that the distance from the emission point to the observation site is critical for sky observation. A series of guidelines were proposed for designing the lighting around observatories, which could help reduce light pollution and increase the stars’ perception. The conclusions and guidelines obtained could also be applied to designing the lighting in other areas, such as protected natural areas, historical monuments, urban lighting, and computer tools used for lighting. Globally, the results obtained in this study could help to reduce the level of night-time light pollution in rural areas, leading to improvements in the environment and in the observation of the night sky. This finding is of great relevance for astronomical observatories, which are spread around the world in strategic positions for sky observation, usually in rural areas.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su15129359
    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
    Differential Stomatal Responses to Surface Permeability by Sympatric Urban Tree Species Advance Novel Mitigation Strategy for Urban Heat Islands
    MDPI AG ; 2023
    In:  Sustainability Vol. 15, No. 15 ( 2023-08-03), p. 11942-
    Details
    In: Sustainability, MDPI AG, Vol. 15, No. 15 ( 2023-08-03), p. 11942-
    Abstract: As urbanization draws more people to metropolitan areas, a steadfast increase in impervious surfaces ultimately contributes to a pronounced urban heat island effect. While city greening strategies to mitigate urban thermal effects often tout street-tree cover expansion, many plant species are susceptible to heat stress, limiting survivorship, primary productivity, and ecosystem services. Our research objective was to characterize how urban imperviousness impacted the photosynthetic traits of four sympatric tree species in Old Town La Verne, California. We found that while Camphor trees (Camphora officinarum) and Carrotwood trees (Cupaniopsis anacardioides) did not differ significantly in photosynthetic traits at sites with impervious and pervious surfaces, both Coast Live Oak trees (Quercus agrifolia) and Olive trees (Olea europaea) showed significant differences in leaf stomatal length and density. Our findings suggest that the photosynthetic traits of some exotic tree species may be less susceptible to surface permeability than either native or floristically indigenous tree species. We propose that urban greening initiatives adopt a temporal strategy for mitigating urban heat island effects, starting with an urban canopy composed of exotic trees more resilient to impervious surfaces and later transitioning to a recombinant canopy ecology of floristically relevant tree species suited for the soil permeability native to southern California.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su151511942
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518383-7
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  • 10
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    Online Resource
    HIV Pretreatment Drug Resistance Trends in Mexico City, 2017–2020
    MDPI AG ; 2021
    In:  Pathogens Vol. 10, No. 12 ( 2021-12-08), p. 1587-
    Details
    In: Pathogens, MDPI AG, Vol. 10, No. 12 ( 2021-12-08), p. 1587-
    Abstract: In response to increasing pretreatment drug resistance (PDR), Mexico changed its national antiretroviral treatment (ART) policy, recommending and procuring second-generation integrase strand-transfer inhibitor (INSTI)-based regimens as preferred first-line options since 2019. We present a four-year observational study describing PDR trends across 2017–2020 at the largest HIV diagnosis and primary care center in Mexico City. A total of 6688 baseline protease-reverse transcriptase and 6709 integrase sequences were included. PDR to any drug class was 14.4% (95% CI, 13.6–15.3%). A significant increasing trend for efavirenz/nevirapine PDR was observed (10.3 to 13.6%, p = 0.02). No increase in PDR to second-generation INSTI was observed, remaining under 0.3% across the study period. PDR was strongly associated with prior exposure to ART (aOR: 2.9, 95% CI: 1.9–4.6, p 〈 0.0001). MSM had higher odds of PDR to efavirenz/nevirapine (aOR: 2.0, 95% CI: 1.0–3.7, p = 0.04), reflecting ongoing transmission of mutations such as K103NS and E138A. ART restarters showed higher representation of cisgender women and injectable drug users, higher age, and lower education level. PDR to dolutegravir/bictegravir remained low in Mexico City, although further surveillance is warranted given the short time of ART optimization. Our study identifies demographic characteristics of groups with higher risk of PDR and lost to follow-up, which may be useful to design differentiated interventions locally.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    URL: Article
    DOI: 10.3390/pathogens10121587
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2695572-6
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