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1.
ACS Omega ; 9(29): 31196-31219, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39072093

RESUMO

Perovskite solar cells (PSCs) are becoming a promising and revolutionary advancement within the photovoltaic field globally. Continuous improvement in efficiency, straightforward processing methods, and use of lightweight and cost-effective materials represent superior features, among other notable aspects. Still, long-term stability and durability are issues to address to facilitate widespread commercial adoption and practical application prospects. Research has focused on overcoming these challenges, and charge transport materials play a critical role in determining charge dynamics, photovoltaic performance, and device stability. Conventional hole-transporting materials (HTMs), spiro-OMeTAD and PTAA, contribute to remarkable power conversion efficiencies owing to high thin-film quality and matched energy alignment. However, they often show a high material cost, low carrier mobility, and poor stability, which greatly limit their practical applications. Now, this review outlines recent advances in synthetic approaches to porphyrin-based HTMs to tune the charge dynamics by optimizing their molecular structures and properties. The main structural features comprise porphyrins of A4-type, trans A2B2-type, and photosynthetic pigment analogues. Strategies include well-established routes to provide the required macrocycles, such as condensation of pyrrole or dipyrromethanes with suitable aldehydes, metalation of the porphyrin inner core, and postfunctionalization of peripheral positions. These functionalizations involve conventional procedures (e.g., halogenation, esterification, transesterification, nucleophilic oxidation, reduction, and nucleophilic substitution) as well as metal-catalyzed ones such as Suzuki-Miyaura, Sonogashira, Buchwald-Hartwig, and Ullmann cross-coupling reactions. As HTMs can also protect the perovskite layer from the external environment, porphyrin structures play a pivotal role in chemical, mechanical, and environmental stability, with their high hydrophobicity ability as the most significant parameter. The impact of porphyrins on the hole hopping of other HTMs while acting as an additive or an interlayer, passivating defects, and improving charge transport is also highlighted to provide real insights into ways to develop efficient and stable porphyrin-based materials for PSCs. This perspective aims to guide the scientific community in the design of new porphyrin molecules to place PSCs as an outperformer in photovoltaic technologies.

2.
Allergy ; 78(10): 2581-2595, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37641384

RESUMO

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

3.
Dalton Trans ; 52(41): 14762-14773, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37548588

RESUMO

A new series of Zn(II) and Cu(II)-based porphyrin complexes 5a and 5b doubly functionalised with carbazole units were developed to be used as hole-transporting materials (HTMs) in perovskite solar cells (PSCs). These complexes were obtained via a nucleophilic substitution reaction mediated by PhI(OAc)2/NaAuCl4·2H2O, or using C-N transition metal-assisted coupling. The hole extraction capability of 5a and 5b was assessed using cyclic voltammetry; this study confirmed the better alignment of the Zn(II) complex 5a with the perovskite valence band level, compared to the Cu(II) complex 5b. The optimised geometry and molecular orbitals of both complexes also corroborate the higher potential of 5a as a HTM. Photoluminescence characterisation showed that the presence of 5a and 5b as HTMs on the perovskite surface resulted in the quenching of the emission, matching the hole transfer phenomenon. The photovoltaic performance was evaluated and compared with those of reference cells made with the standard HTM spiro-OMeTAD. The optimised 5-based devices showed improvements in all photovoltaic characteristics; their open circuit voltage (Voc) reached close to 1 V and short-circuit current density (Jsc) values were 13.79 and 9.14 mA cm-2 for 5a and 5b, respectively, disclosing the effect of the metallic centre. A maximum power conversion efficiency (PCE) of 10.01% was attained for 5a, which is 65% of the PCE generated by using the spiro-OMeTAD reference. This study demonstrates that C-N linked donor-type porphyrin derivatives are promising novel HTMs for developing efficient and reproducible PSCs.

4.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675195

RESUMO

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 ± 0.58 kg/m2) or class 3 (n = 8; BMI 47.79 ± 1.52 kg/m2) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment.


Assuntos
Glutamina , Gordura Intra-Abdominal , Humanos , Glutamina/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Metabolismo Energético , Piruvatos/metabolismo , Tecido Adiposo/metabolismo
5.
Laryngoscope ; 133(6): 1321-1327, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35912902

RESUMO

OBJECTIVES: Allergic rhinitis (AR) has been associated with anxiety and depression. A possible influence of frequency and intensity of the AR symptoms has remained unclear. Therefore, we evaluated the association between AR, as well as its control, seasonality and severity, and the presence of anxiety and depression. METHODS: Participants were selected from a preexistent national database and consecutively contacted by phone. AR was classified according to Allergic Rhinitis and its Impact on Asthma. Presence of anxiety and depression was identified by Hospital Anxiety and Depression Scale (HADS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II (BDI-II). We built linear regression models assessing the association between any of the assessed anxiety or depression scores and the occurrence, degree of control, seasonality or severity of AR. RESULTS: We analyzed 115 participants with AR and 38 participants with no respiratory symptoms. Patients with AR presented higher scores of anxiety (HADS: 3.1; 95% confidence interval [CI] = 1.9; 4.3; p < 0.001) and depression (HADS: 3.8; 95% CI = 2.5; 5.0; p < 0.001). Poorer AR control was positively associated with higher prevalence and scores of anxiety (HADS: 3.0; 95% CI = 1.5; 4.5; p < 0.001) and depression (HADS: 1.8; 95% CI = 0.2; 3.4; p = 0.031). Similar results were obtained with BAI and BDI-II scales. A moderate/severe presentation of AR were also related with higher scores of anxiety (HADS: 1.7; 95% CI = 0.1; 3.2; p = 0.040) and depression (HADS: 1.7; 95% CI = 0.1; 3.3; p = 0.037). CONCLUSION: The presence of AR, a poorer control, and a moderate/severe presentation of the disease were significantly associated with higher scores of anxiety and depression. Thus, it is important to alert to this association to allow a quick diagnosis of AR-associated pathologies. Laryngoscope, 133:1321-1327, 2023.


Assuntos
Asma , Rinite Alérgica , Humanos , Depressão/epidemiologia , Depressão/etiologia , Depressão/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Ansiedade/diagnóstico , Transtornos de Ansiedade/diagnóstico , Rinite Alérgica/complicações , Rinite Alérgica/epidemiologia , Asma/complicações , Asma/epidemiologia
6.
Foods ; 11(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36496561

RESUMO

Mannans are outstanding polysaccharides that have gained exponential interest over the years. These polysaccharides may be extracted from the cell wall of Saccharomyces cerevisiae, and recovered from the brewing or synthetic biology industries, among others. In this work, several extraction processes-physical, chemical and enzymatic-were studied, all aiming to obtain mannans from spent yeast S. cerevisiae. Their performance was evaluated in terms of yield, mannose content and cost. The resultant extracts were characterized in terms of their structure (FT-IR, PXRD and SEM), physicochemical properties (color, molecular weight distribution, sugars, protein, ash and water content) and thermal stability (DSC). The biological properties were assessed through the screening of prebiotic activity in Lactobacillus plantarum and Bifidobacterium animalis. The highest yield (58.82%) was achieved by using an alkaline thermal process, though the correspondent mannose content was low. The extract obtained by autolysis followed by a hydrothermal step resulted in the highest mannose content (59.19%). On the other hand, the extract obtained through the enzymatic hydrolysis displayed the highest prebiotic activity. This comparative study is expected to lay the scientific foundation for the obtention of well-characterized mannans from yeast, which will pave the way for their application in various fields.

7.
Oncogene ; 41(32): 3969-3977, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35768547

RESUMO

HORMAD1 expression is usually restricted to germline cells, but it becomes mis-expressed in epithelial cells in ~60% of triple-negative breast cancers (TNBCs), where it is associated with elevated genomic instability (1). HORMAD1 expression in TNBC is bimodal with HORMAD1-positive TNBC representing a biologically distinct disease group. Identification of HORMAD1-driven genetic dependencies may uncover novel therapies for this disease group. To study HORMAD1-driven genetic dependencies, we generated a SUM159 cell line model with doxycycline-inducible HORMAD1 that replicated genomic instability phenotypes seen in HORMAD1-positive TNBC (1). Using small interfering RNA screens, we identified candidate genes whose depletion selectively inhibited the cellular growth of HORMAD1-expressing cells. We validated five genes (ATR, BRIP1, POLH, TDP1 and XRCC1), depletion of which led to reduced cellular growth or clonogenic survival in cells expressing HORMAD1. In addition to the translesion synthesis (TLS) polymerase POLH, we identified a HORMAD1-driven dependency upon additional TLS polymerases, namely POLK, REV1, REV3L and REV7. Our data confirms that out-of-context somatic expression of HORMAD1 can lead to genomic instability and reveals that HORMAD1 expression induces dependencies upon replication stress tolerance pathways, such as translesion synthesis. Our data also suggest that HORMAD1 expression could be a patient selection biomarker for agents targeting replication stress.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas de Ciclo Celular/genética , Dano ao DNA/genética , Reparo do DNA , Replicação do DNA/genética , Proteínas de Ligação a DNA/genética , DNA Polimerase Dirigida por DNA/genética , Instabilidade Genômica/genética , Humanos , Nucleotidiltransferases/genética , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética
8.
Front Psychol ; 12: 596434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868076

RESUMO

Esports, including virtual football, are a worldwide phenomenon. Yet, little is known about the physical activity levels of individuals engaged in virtual football game play. Therefore, we aimed to perform a preliminary evaluation of the levels of physical activity, sedentarism, and habits of physical training of adults engaged with virtual football in Portugal. This was a cross-sectional investigation based on a structured online survey using the International Physical Activity Questionnaire (IPAQ) and a set of questions regarding habits of physical training. The participants (n = 433) reported spending a median of 5,625 MET-min⋅week-1 being physically active. Still, the participants spent 320 min/day sitting, and 150 min/day practicing virtual football. According to the IPAQ scores, high physical activity levels were reported by 84.5% of the participants, and 87.1% were considered physically active considering the WHO guidelines on physical activity and sedentary behavior. Overall, 60.0% of the participants reported planning their own physical training. Maintaining or improving overall physical health was one of the main reasons for doing physical training (66.7%), with only 6.1% responding being active to improve virtual football performance. Overall, the results showed that virtual football players accomplished the standard recommendations for physical activity, with high levels of physical activity, and encompassing regular physical training focused mostly on health promotion, rather than improved virtual football performance.

9.
Allergy ; 76(10): 3041-3052, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33492738

RESUMO

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.


Assuntos
Hipersensibilidade Alimentar , Rinite Alérgica Sazonal , Alérgenos , Reações Cruzadas , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Humanos , Pólen , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/epidemiologia , Testes Cutâneos
10.
ACS Biomater Sci Eng ; 7(2): 451-461, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33492122

RESUMO

The increasing bacterial resistance to antibiotics is driving strong demand for new antimicrobial biomaterials. This work describes the fabrication of free-standing films exhibiting antimicrobial properties by combining, in the same polypeptide chain, an elastin-like recombinamer comprising 200 repetitions of the pentamer VPAVG (A200) and an 18-amino-acid truncated variant of the antimicrobial peptide BMAP-28, termed BMAP-18. The fusion protein BMAP-18A200 was overexpressed and conveniently purified by a simplified and scalable nonchromatographic process. Free-standing films of BMAP-18A200 demonstrated to be stable without requiring cross-linking agents and displayed high antimicrobial activity against skin pathogens including Gram-negative and Gram-positive bacteria as well as unicellular and filamentous fungi. The antimicrobial activity of the films was mediated by direct contact of cells with the film surface, resulting in compromised structural integrity of microbial cells. Furthermore, the BMAP-18A200 films showed no cytotoxicity on normal human cell lines (skin fibroblasts and keratinocytes). All of these results highlight the potential of these biotechnological multifunctional polymers as new drug-free materials to prevent and treat microbial infections.


Assuntos
Anti-Infecciosos , Sequência de Aminoácidos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias Gram-Positivas , Humanos , Proteínas Citotóxicas Formadoras de Poros
11.
J Anal Methods Chem ; 2020: 8821809, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32953194

RESUMO

Zinc is an essential trace element for animals in several biological processes, particularly in energy production, and it is acquired from food ingestion. In this context, a microplate-based fluorimetric assay was developed for simple, fast, and low-cost determination of zinc in pet food using 2,2'-((4-(2,7-difluoro-3,6-dihydroxy-4aH-xanthen-9-yl)-3-methoxyphenyl)azanediyl)diacetic acid (FluoZin-1) as fluorescent probe. Several aspects were studied, namely, the stability of the fluorescent product over time, the FluoZin-1 concentration, and the pH of reaction media. The developed methodology provided a limit of detection of 1 µg L-1 in sample acid digests, with a working range of 10 to 200 µg L-1, corresponding to 100-2000 mg of Zn per kg of dry dog food samples. Intraday repeatability and interday repeatability were assessed, with relative standard deviation values < 3.4% (100 µg L-1) and <11.7% (10 µg L-1). Sample analysis indicated that the proposed fluorimetric assay provided results consistent with ICP-MS analysis. These results demonstrated that the developed assay can be used for rapid determination of zinc in dry dog food.

12.
Eur J Pharmacol ; 885: 173390, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32735983

RESUMO

Erythrinian alkaloids ((+)-erythravine and (+)-11-α-hydroxy-erythravine) have been pointed as the main responsible agents for the anticonvulsant and anxiolytic properties of Erythrina mulungu Mart ex Benth. The present work provides a new set of information about the mode of action of these alkaloids by the use of a complementary approach of neurochemical and electrophysiological assays. We propose here that the antiepileptic and anxiolytic properties exhibited by both alkaloids appear not to be related to the inhibition of glutamate binding or GABA uptake, or even to the increase of glutamate uptake or GABA binding, as investigated here by the use of rat cortical synaptosomes. Similarly, and even in a high concentration, (+)-erythravine and (+)-11-α-hydroxy-erythravine did not modulate the main sodium and potassium channel isoforms checked by the use of voltage-clamp studies on Xenopus laevis oocytes. However, unlike (+)-11-α-hydroxy-erythravine, which presented a little effect, it was possible to observe that the (+)-erythravine alkaloid produced a significant inhibitory modulation on α4ß2, α4ß4 and α7 isoforms of nicotinic acetylcholine receptors also checked by the use of voltage-clamp studies, which could explain at least partially its anxiolytic and anticonvulsant properties. Since (+)-11-α-hydroxy-erythravine and (+)-erythravine modulated nicotinic acetylcholine receptors to different extents, it is possible to reinforce that small differences between the chemical structure of these alkaloids can affect the selectivity and affinity of target-ligand interactions, conferring distinct potency and/or pharmacological properties to them, as previously suggested by differential experimental comparison between different erythrinian alkaloids.


Assuntos
Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Erythrina/química , Ácido Glutâmico/metabolismo , Antagonistas Nicotínicos/farmacologia , Oócitos , Técnicas de Patch-Clamp , Potássio/metabolismo , Receptores Nicotínicos/efeitos dos fármacos , Canais de Sódio/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Xenopus laevis , Ácido gama-Aminobutírico/metabolismo
13.
Obes Surg ; 30(10): 4019-4028, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32564307

RESUMO

PURPOSE: Biliopancreatic diversion with duodenal switch (BPD-DS) is an effective weight loss surgical procedure. Yet, BPD-DS is technically difficult to perform and carries a higher risk of nutrient deficiencies as compared with other surgical interventions. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modified BPD-DS procedure conceived with the aim of decreasing the technical complexity, while retaining the weight loss efficiency. Whether the two surgical procedures diverge in nutrient absorption rates and malnutrition risk is still matter of debate. Our aim was to determine if postprandial nutrient absorption rates are different in patients subjected to BPD-DS or SADI-S for weight loss. MATERIALS AND METHODS: Plasma amino acid metabolomic profiling during mixed-meal tolerance test (MMTT) was performed in subjects (N = 18) submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.6 ± 0.1 years earlier. RESULTS: Patients submitted to SADI-S or BPD-DS presented distinct postprandial metabolomic profiles. Postprandial excursions of total and essential amino acids-leucine, isoleucine, and valine-were higher after SADI-S as compared with BPD-DS. CONCLUSION: Our study demonstrates that a simplified malabsorptive bariatric surgery procedure SADI-S results in greater essential branched-chain amino acid absorption when compared with the classical BPD-DS intervention. These findings suggest that SADI-S can potentially lower lifetime risk of postoperative protein malnutrition, as well as have a positive impact on systemic metabolism and glucose homeostasis.


Assuntos
Cirurgia Bariátrica , Desvio Biliopancreático , Obesidade Mórbida , Aminoácidos , Duodeno , Gastrectomia , Humanos , Obesidade Mórbida/cirurgia
14.
J Nat Prod ; 83(5): 1409-1415, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32372647

RESUMO

Citrus sinensis and Citrus limonia were obtained by germination from seeds, and isotopic-labeling experiments using d-[1-13C]glucose were performed with the seedlings. After 60 days, the seedlings were analyzed by high-performance liquid chromatography-ultraviolet-solid-phase extraction-nuclear magnetic resonance, data and the 13C enrichment patterns of xanthyletin and seselin indicated that the pyran ring was formed by the methylerythritol phosphate pathway and that the coumarin moiety was derived from the shikimate pathway in both compounds. This information regarding the biosynthetic pathway can be used to increase resistance against phytopathogens, because xanthyletin and seselin are reported to have antimicrobial activity on the growth of Xylella fastidiosa, which causes citrus variegated chlorosis in orange.


Assuntos
Marcação por Isótopo/métodos , Piranocumarinas/metabolismo , Isótopos de Carbono , Cromatografia Líquida de Alta Pressão , Citrus/metabolismo , Citrus sinensis/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Doenças das Plantas/microbiologia , Piranocumarinas/química , Piranocumarinas/isolamento & purificação , Ácido Chiquímico/metabolismo , Extração em Fase Sólida , Espectrofotometria Ultravioleta , Xylella/efeitos dos fármacos
15.
J Appl Biomater Funct Mater ; 17(4): 2280800019848923, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31623515

RESUMO

INTRODUCTION: The success of a bioartificial pancreas crucially depends on ameliorating encapsulated beta cells survival and function. By mimicking the cellular in vivo niche, the aim of this study was to develop a novel model for beta cells encapsulation capable of establishing an appropriate microenvironment that supports interactions between cells and extracellular matrix (ECM) components. METHODS: ECM components (Arg-Gly-Asp, abbreviated as RGD) were chemically incorporated in alginate hydrogels (alginate-RGD). After encapsulation, INS-1E beta cells outcome was analyzed in vitro and after their implantation in an animal model of diabetes. RESULTS: Our alginate-RGD model demonstrated to be a good in vitro niche for supporting beta cells viability, proliferation, and activity, namely by improving the key feature of insulin secretion. RGD peptides promoted cell-matrix interactions, enhanced endogenous ECM components expression, and favored the assembly of individual cells into multicellular spheroids, an essential configuration for proper beta cell functioning. In vivo, our pivotal model for diabetes treatment exhibited an improved glycemic profile of type 2 diabetic rats, where insulin secreted from encapsulated cells was more efficiently used. CONCLUSIONS: We were able to successfully introduce a novel valuable function in an old ally in biomedical applications, the alginate. The proposed alginate-RGD model stands out as a promising approach to improve beta cells survival and function, increasing the success of this therapeutic strategy, which might greatly improve the quality of life of an increasing number of diabetic patients worldwide.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Matriz Extracelular/química , Hidrogéis/química , Secreção de Insulina , Oligopeptídeos/química , Pâncreas Artificial , Animais , Linhagem Celular Tumoral , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Ratos
16.
Sci Rep ; 9(1): 12911, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501484

RESUMO

Induced morphology changes of cells and organelles are by far the easiest way to determine precise protein sub-locations and organelle quantities in light microscopy. By using hypotonic solutions to swell mammalian cell organelles we demonstrate that precise membrane, lumen or matrix protein locations within the endoplasmic reticulum, Golgi and mitochondria can reliably be established. We also show the benefit of this approach for organelle quantifications, especially for clumped or intertwined organelles like peroxisomes and mitochondria. Since cell and organelle swelling is reversible, it can be applied to live cells for successive high-resolution analyses. Our approach outperforms many existing imaging modalities with respect to resolution, ease-of-use and cost-effectiveness without excluding any co-utilization with existing optical (super)resolution techniques.


Assuntos
Forma Celular , Soluções Hipotônicas , Organelas , Animais , Linhagem Celular , Humanos , Microscopia de Fluorescência , Imagem Óptica , Organelas/metabolismo , Transporte Proteico
17.
Molecules ; 24(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510078

RESUMO

Uncaria tomentosa (Rubiaceae) has a recognized therapeutic potential against various diseases associated with oxidative stress. The aim of this research was to evaluate the antioxidant potential of an aqueous leaf extract (ALE) from U. tomentosa, and its major alkaloids mitraphylline and isomitraphylline. The antioxidant activity of ALE was investigated in vitro using standard assays (DPPH, ABTS and FRAP), while the in vivo activity and mode of action were studied using Caenorhabditis elegans as a model organism. The purified alkaloids did not exhibit antioxidant effects in vivo. ALE reduced the accumulation of reactive oxygen species (ROS) in wild-type worms, and was able to rescue the worms from a lethal dose of the pro-oxidant juglone. The ALE treatment led to a decreased expression of the oxidative stress response related genes sod-3, gst-4, and hsp-16.2. The treatment of mutant worms lacking the DAF-16 transcription factor with ALE resulted in a significant reduction of ROS levels. Contrarily, the extract had a pro-oxidant effect in the worms lacking the SKN-1 transcription factor. Our results suggest that the antioxidant activity of ALE in C. elegans is independent of its alkaloid content, and that SKN-1 is required for ALE-mediated stress resistance.


Assuntos
Antioxidantes/química , Unha-de-Gato/química , Alcaloides Indólicos/farmacologia , Oxindóis/farmacologia , Alcaloides/química , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxindóis/química , Extratos Vegetais/química , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo
18.
Clin Transl Allergy ; 9: 17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918624

RESUMO

BACKGROUND: Half of the adults with current asthma among the US National Health and Nutrition Examination Survey (NHANES) participants could be classified in more than one hypothesis-driven phenotype. A data-driven approach applied to the same subjects may allow a more useful classification compared to the hypothesis-driven one. AIM: To compare previously defined hypothesis-driven with newly derived data-driven asthma phenotypes, identified by latent class analysis (LCA), in adults with current asthma from NHANES 2007-2012. METHODS: Adults (≥ 18 years) with current asthma from the NHANES were included (n = 1059). LCA included variables commonly used to subdivide asthma. LCA models were derived independently according to age groups: < 40 and ≥ 40 years old. RESULTS: Two data-driven phenotypes were identified among adults with current asthma, for both age groups. The proportions of the hypothesis-driven phenotypes were similar among the two data-driven phenotypes (p > 0.05). Class A < 40 years (n = 285; 75%) and Class A ≥ 40 years (n = 462; 73%), respectively, were characterized by a predominance of highly symptomatic asthma subjects with poor lung function, compared to Class B < 40 years (n = 94; 25%) and Class B ≥ 40 years (n = 170; 27%). Inflammatory biomarkers, smoking status, presence of obesity and hay fever did not markedly differ between the phenotypes. CONCLUSION: Both data- and hypothesis-driven approaches using clinical and physiological variables commonly used to characterize asthma are suboptimal to identify asthma phenotypes among adults from the general population. Further studies based on more comprehensive disease features are required to identify asthma phenotypes in population-based studies.

19.
Int J Obes (Lond) ; 43(12): 2518-2527, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30538284

RESUMO

BACKGROUND/OBJECTIVE: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective bariatric intervention to treat morbid obesity and related disorders. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new bariatric procedure devised with the purpose of simplifying the complexity of the BPD-DS technique while maintaining its efficacy. However, whether BPD-DS and SADI-S result in similar fasting and post-prandial hormone profiles has not yet been studied. Therefore, the purpose of this study was to assess and compare the hormone response to a standardized mixed meal in subjects operated with BPD-DS or SADI-S. SUBJECTS/METHODS: Subjects submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.5 years earlier on average, with no past nor current diabetes diagnosis underwent a liquid mixed-meal tolerance test (MMTT) to assess the baseline and post-prandial profile of glucose, enteropancreatic hormones and total bile acids. RESULTS: Fasting glucose, enteropancreatic hormones and total bile acids levels after BPD-DS and SADI-S were similar. After the MMTT, the response of subjects who underwent SADI-S was characterized by higher glucose (t = 30 min: p < 0.05; iAUC: 156.1 ± 46.2 vs. 103.4 ± 35.8 mmol/L × min, p = 0.02), GLP-1 (t = 30 min: p < 0.05; iAUC: 5388 ± 3010 vs. 2959.0 ± 2146 pmol/L × min, p = 0.02), glucagon (t = 30 min: p < 0.05; iAUC: 678.7 ± 295.2 vs. 376.9 ± 215.7 pmol/L × min, p = 0.02), insulin (t = 30 and 45 min: p < 0.05); and C-peptide levels (t = 30 and 45 min: p < 0.05), when compared to BPD-DS. CONCLUSIONS: The post-prandial hormone secretion profile after SADI-S is characterized by increased GLP-1, glucagon and insulin secretion, when compared to BPD-DS, which suggests the existence of different endocrine driven mechanisms leading to weight loss and metabolic improvement after the two procedures.


Assuntos
Cirurgia Bariátrica/métodos , Desvio Biliopancreático/métodos , Hormônios Gastrointestinais/sangue , Período Pós-Prandial/fisiologia , Adulto , Anastomose Cirúrgica , Estudos de Coortes , Duodeno/cirurgia , Feminino , Gastrectomia , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Adulto Jovem
20.
Allergy ; 74(4): 698-708, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30447164

RESUMO

BACKGROUND: Refined phenotyping of allergic diseases may unravel novel phenotypes. Conjunctivitis as an independent disorder has never been approached. AIM: To identify distinct classes of allergic respiratory diseases using latent class analysis (LCA) and distinguish each class using classification and regression tree (CART) analysis. METHODS: Seven hundred and twenty-eight adults from the Portuguese general population study ICAR had a structured medical interview combined with blood collection, skin prick tests, spirometry with bronchodilation, and exhaled nitric oxide. LCA was applied to 19 variables. The CART algorithm selected the most likely variables distinguishing LCA-classes. RESULTS: A six-class model was obtained. Class 1 (25%): nonallergic participants without bronchial or ocular symptoms. Classes 2 (22%) and 3 (11%): nasal and ocular (low levels) symptoms without nasal impairment, monosensitized (Class 2) or polysensitized (Class 3). Class 4 (13%): polysensitized participants with high levels of nasal and ocular symptoms, and nasal impairment. Classes 5 (16%) and 6 (14%): high level of nasal, bronchial and ocular symptoms with nasal impairment (non-allergic or polysensitized, respectively). Participants in classes 5 and 6 had more bronchial exacerbations and unscheduled medical visits (P < 0.001). Ocular symptoms were significantly higher in classes with nasal impairment, compared to those without impairment (P < 0.001) or no nasal symptom (P < 0.001). CART highlighted ocular symptoms as the most relevant variable in distinguishing LCA-classes. CONCLUSION: Novel severe phenotypes of participants with co-occurrence of ocular, nasal and bronchial symptoms, and exacerbation-prone were identified. The tree algorithm showed the importance of the ocular symptoms in the expression of allergic diseases phenotypes.


Assuntos
Asma/diagnóstico , Oftalmopatias/imunologia , Análise de Classes Latentes , Adulto , Algoritmos , Asma/classificação , Conjuntivite , Oftalmopatias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Portugal
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