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1.
medRxiv ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38699354

ABSTRACT

During the ongoing western equine encephalitis virus (WEEV) outbreak in South America, we described three fatal cases in horses from Rio Grande do Sul, Brazil. We sequenced WEEV strains and identified a novel lineage causing these cases. Continued surveillance and horse immunization are needed to mitigate the WEEV burden.

2.
Sci Total Environ ; 931: 172961, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38705309

ABSTRACT

Whether fresh or salty, water is a unique resource, a continuum interlinked by the hydrological cycle. It forms a complex system connected to the landscape. When the landscape is altered, water flows and their benefits are impacted. Degraded land compromises water resources. The governance and management of landscape and water resources are handled in a fragmented manner and in separate contexts. The Source-to-Sea approach offers an integrative vision based on systems thinking that focuses its concerns on the interaction among parts, flows, and processes. It proposes a framework for the governance and management of freshwater and marine water but does not bring the landscape into the context of the approach. This research used an analytical-deductive method to explore the interactions and connections between the Source-to-sea approach, landscape concepts and approaches, and the guidelines of the European Landscape Convention. The main objective was to identify and assess the feasibility of integrating these elements. The integration resulted in a governance and management approach termed the S2S Landscape approach. It is grounded in systems thinking, practical learning, active participation, and adaptive governance and management, providing an integrated vision between landscape and water. The approach includes four essential steps (Comprehension, Involvement, Planning, and Execution and Monitoring) that address the complex connections that freshwater and marine water maintain in the landscape, considering physical, biological, socio-environmental, and economic aspects across all segments, from the land to the open sea. This S2S Landscape approach may be the path to address the challenges of governance and sustainable management of resources in an interconnected and constantly changing world.

3.
Int J Biol Macromol ; 263(Pt 2): 130279, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38401585

ABSTRACT

Despite ortho-quinones showing several biological and pharmacological activities, there is still a lack of biophysical characterization of their interaction with albumin - the main carrier of different endogenous and exogenous compounds in the bloodstream. Thus, the interactive profile between bovine serum albumin (BSA) with ß-lapachone (1) and its corresponding synthetic 3-sulfonic acid (2, under physiological pH in the sulphonate form) was performed. There is one main binding site of albumin for both ß-lapachones (n ≈ 1) and a static fluorescence quenching mechanism was proposed. The Stern-Volmer constant (KSV) values are 104 M-1, indicating a moderate binding affinity. The enthalpy (-3.41 ± 0.45 and - 8.47 ± 0.37 kJ mol-1, for BSA:1 and BSA:2, respectively) and the corresponding entropy (0.0707 ± 0.0015 and 0.0542 ± 0.0012 kJ mol-1 K-1) values indicate an enthalpically and entropically binding driven. Hydrophobic interactions and hydrogen bonding are the main binding forces. The differences in the polarity of 1 and 2 did not change significantly the affinity to albumin. In addition, the 1,2-naphthoquinones showed a similar binding trend compared with 1,4-naphthoquinones.


Subject(s)
Naphthoquinones , Protein Binding , Spectrometry, Fluorescence , Binding Sites , Thermodynamics , Serum Albumin, Bovine/chemistry , Circular Dichroism
4.
Article in English | MEDLINE | ID: mdl-38111113

ABSTRACT

INTRODUCTION: Mitochondrial oxidative phosphorylation (OXPHOS) diseases are challenging both from clinical and therapeutic perspectives. The advent of next-generation sequencing (NGS) boosted the discovery of new genetic defects affecting OXPHOS, with pathogenic variants identified in >350 genes to date [1]. However, in many patients, novel variants of unknown clinical significance are found. Subsequent functional studies may clarify its pathogenic consequences and modify the variant's classification, establishing a genetic diagnosis [2, 3]. METHODS: Analysis of data obtained from patients (P1-P5) with novel genetic causes and functional genomics' studies performed, namely OXPHOS respiratory/glycolytic rates (Seahorse XF), enzymatic activity and assembly (BN-page), protein levels (SDS-WB), single muscle fiber assay, NGS and bioinformatics. RESULTS/CASE REPORT: P1-Leigh syndrome (40y, male); Complex IV activity deficiency (full assembly absent), homozygous deletion (c.-11_13del, SURF1), not detected by NGS[2]. P2- Epileptic encephalopathy (8y, male); homozygous c.882-1G>A, FASTKD2; OXPHOS decrease; reduced FASTKD2 expression and abnormal respiratory/glycolytic rates. P3-Cardiomyopathy/ nephropathy (39y, male); c.29G>C, FASTKD2; OXPHOS decrease; reduced FASTKD2 levels. P4-CPEO (62y, female); multiple OXPHOS deficiency; mtDNA alterations (m.7486G>A, MTTS1; 4,977bp del); higher levels of mutant mtDNA alterations in COX-deficient fibers [3]. P5- Polyneuropathy (15y, female); heterozygous c.1437C>A, POLG; combined def. or normal OXPHOS activity/respiratory capacity (tissue variable), raised CI assembly; normal POLG levels. Also, proteins' expression levels were reduced (P1-4), confirming pathogenicity. In P5, data do not support pathogenicity. CONCLUSION: If specific functional results are similar to controls, one might inquire about the pathogenicity of the studied variant and more genetic or bioinformatics analyses and family investigations are needed. There are also limitations of NGS in mutation detection that Sanger sequencing can overcome (P1). When performed first, the OXPHOS activity may guide to genetic screening or interpretation, concordant to later assembly results. All cases were solved and data may be crucial for genetic counseling.

6.
Article in English | MEDLINE | ID: mdl-36554567

ABSTRACT

Coastal areas are home to more than 2 billion people around the globe and, as such, are especially vulnerable to climate change consequences. Climate change adaptation has proven to be more effective on a local scale, contributing to a bottom-up approach to the problems related to the changing climate. Portugal has approximately 2000 km of coastline, with 75% of the population living along the coast. Therefore, this research had the main objective of understanding adaptation processes at a local scale, using Portuguese coastal municipalities as a case study. To achieve this goal, document analysis and a questionnaire to coastal municipalities were applied, and the existence of measures rooted in nature-based solutions, green infrastructures, and community-based adaptation was adopted as a variable. The main conclusion from this research is that 87% of the municipalities that answered the questionnaire have climate change adaptation strategies implemented or in development. Moreover, it was possible to conclude that 90% of the municipalities are familiar with the concept of nature-based solutions and all the municipalities with adaptation strategies include green infrastructure. However, it was also possible to infer that community-based adaptation is a concept that most municipalities do not know about or undervalue.


Subject(s)
Acclimatization , Climate Change , Humans , Portugal , Cities
7.
Genes (Basel) ; 13(12)2022 12 19.
Article in English | MEDLINE | ID: mdl-36553678

ABSTRACT

Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes: STAT1, IRF7, ISG15, MX1 and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.


Subject(s)
COVID-19 , Diabetes Mellitus , Diabetic Nephropathies , Humans , Diabetic Nephropathies/genetics , COVID-19/genetics , SARS-CoV-2 , Kidney , Gene Expression
8.
Transbound Emerg Dis ; 69(6): 3449-3456, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36070102

ABSTRACT

Rabies is an encephalitis caused by rabies virus, whose transmission occurs upon contact with infected animals' saliva. The diagnosis is usually performed post-mortem through a direct fluorescent antibody test (DFAT). If the DFAT results are negative, they must be confirmed with an isolation test, usually the mouse inoculation test (MIT), which implies the suffering and death of the animals, high costs and most importantly, up to 28 days to confirm a negative result. Another issue related to rabies diagnosis is the sample collection and storage, which is critical for the rabies virus' RNA genome. Thus, this study aimed to evaluate (i) reverse transcriptase polymerase chain reaction (RT-PCR) and Rabies Tissue Culture Infection Tests (RTCIT) in comparison to DFAT and MIT and (ii) FTA® cards as an alternative sample collection and preservation method. Eighty animal samples were evaluated through DFAT, RTCIT and RT-PCR; MIT was performed only in DFAT-negative samples. FTA® cards were evaluated with a subset of 64 samples, with sufficient material for imprinting. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV), agreement and Cohen's kappa were calculated for each test combination. RTCIT had higher sensitivity (92.5%) and RT-PCR had higher specificity (92.3%) compared to DFAT. The combination of tests enhanced sensitivity, NPV and Cohen's kappa (considering positive results by RTCIT or RT-PCR), and specificity and PPV (when both tests were concordant). The PCR based on FTA® cards as sample source was specific (84.6%-96.2%) but presented lower sensitivity (29.7%-73.0%), although it could detect as positive four DFAT-negative samples. RTCIT and RT-PCR may be used as confirmatory tests in DFAT-negative samples. Moreover, FTA® cards may be helpful for sample collection in field situations where a long time is needed until the sample undergoes laboratory testing.


Subject(s)
Rabies virus , Rabies , Rodent Diseases , Animals , Mice , Rabies/diagnosis , Rabies/veterinary , Polymerase Chain Reaction/veterinary , Specimen Handling/veterinary , RNA, Viral/analysis , Sensitivity and Specificity , Reverse Transcriptase Polymerase Chain Reaction/veterinary
9.
Int J Biol Macromol ; 160: 1114-1129, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32450323

ABSTRACT

The present work reports the biological assays between synthetic BF2-naphtyridine complexes and four proteins: human serum albumin (HSA), calf-thymus DNA (CT-DNA), tyrosinase and acetylcholinesterase enzymes via spectroscopic analysis at physiological conditions, combined with molecular docking simulations. The BF2-complexes presented spontaneous and moderate binding ability to HSA through the ground-state association (static fluorescence quenching mechanism). The main binding site is Sudlow's site I (subdomain IIA) and the binding does not perturb significantly both secondary and surface structure of HSA. Despite BF2-complexes showed good binding ability with HSA, these compounds presented weak intercalative ability with CT-DNA (the most conventional and simple model to preliminary studies), except in the case of 1 h, which suggested that the presence of electronic donor groups in both aromatic ring moieties of BF2-complex structure can increase the intercalative ability for DNA strands. Competitive binding displacement assays in the presence of methyl green and molecular docking calculations indicated that the studied compounds interact preferentially in the major groove of DNA. In addition, the assayed compounds presented the ability to activate or inhibit both tyrosinase (the decontrolled activity can induce melanoma carcinoma) or AChE (involved in reactions related to the function of neurotransmitters) enzymes.


Subject(s)
Acetylcholinesterase/chemistry , Boron Compounds/chemistry , Cholinesterase Inhibitors/chemical synthesis , Monophenol Monooxygenase/chemistry , Naphthyridines/chemistry , Acetylcholinesterase/metabolism , Binding Sites , Cholinesterase Inhibitors/pharmacology , DNA/chemistry , DNA/metabolism , Humans , Molecular Docking Simulation , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Protein Binding , Serum Albumin/chemistry , Serum Albumin/metabolism
10.
Epilepsia ; 61(2): 216-227, 2020 02.
Article in English | MEDLINE | ID: mdl-31876960

ABSTRACT

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures.


Subject(s)
Epilepsy/surgery , Neurosurgery/trends , Neurosurgical Procedures/trends , Adolescent , Age Factors , Child , Child, Preschool , Electroencephalography , Epilepsy/epidemiology , Epilepsy/pathology , Europe/epidemiology , Female , Humans , Magnetic Resonance Imaging , Male , Neurosurgery/statistics & numerical data , Neurosurgical Procedures/statistics & numerical data , Retrospective Studies , Seizures/epidemiology , Temporal Lobe/diagnostic imaging , Temporal Lobe/surgery , Treatment Outcome
11.
Arq. Inst. Biol ; 87: e0692018, 2020. tab
Article in English | LILACS, VETINDEX | ID: biblio-1118049

ABSTRACT

Bovines and equines are the domestic animals with the highest incidence of rabies in Brazil. This study evaluated the data input in testing request forms for rabies in herbivores accompanying samples sent to a certified laboratory of rabies diagnosis in the state of Rio Grande do Sul, Brazil. Information was obtained systematically from all forms sent to the laboratory in 2013 and 2014 using a collection instrument that listed variables about the kind of form used, municipality of origin, description of the suspected animal, clinical signs, sample collection, and conservation procedure. The 11 most relevant variables (municipality of origin, geographic coordinates, species, gender, breed, age, herd size, clinical signs, persistence of clinical signs, biological material, and sample conservation) were assessed for the quality of the data entered, and percentage data input was calculated per form. In total, 603 forms were sent to the laboratory. The most used form was the FORM SN, (82.0%, 497/603). "Excellent" and "good" data inputs were observed only for one variable describing the location of suspected rabies cases or outbreaks and animals (species, gender, biological material). Quality of data input of variables describing geographic coordinates, age, breed, herd size, clinical signs, persistence of signs, and sample conservation method varied between "average" and "poor". The data input in testing request forms for herbivores are not dully supplied in suspected cases neurological syndromes, pointing to the need to increase awareness and improve training of field staff.(AU)


Bovinos e equinos são os animais domésticos com maior incidência de raiva no Brasil. Este estudo avaliou formulários de solicitação de testes para raiva em herbívoros acompanhando amostras enviadas a um laboratório certificado de diagnóstico de raiva no estado do Rio Grande do Sul, Brasil. As informações foram obtidas sistematicamente de todos os formulários enviados ao laboratório em 2013 e 2014 utilizando um instrumento de coleta que selecionou variáveis sobre o tipo de formulário utilizado, município de origem, descrição do animal suspeito, sinais clínicos, coleta de amostra e procedimento de conservação. As 11 variáveis mais relevantes (município de origem, coordenadas geográficas, espécie, gênero, raça, idade, tamanho do rebanho, sinais clínicos, persistência de sinais clínicos, material biológico e conservação da amostra) foram avaliadas quanto à qualidade dos dados inseridos, e os dados percentuais foram calculados por formulário. No total, 603 formulários foram enviados para o laboratório. O formulário mais utilizado foi o FORM SN, (82,0%, 497/603). Dados classificados como "excelentes" e "bons" foram observados apenas para uma variável que descreve a localização de casos suspeitos de raiva ou surtos e animais (espécie, gênero, material biológico). A qualidade da entrada dos dados das variáveis que descrevem coordenadas geográficas, idade, raça, tamanho do rebanho, sinais clínicos, persistência de sinais e método de conservação da amostra variou entre "regular" e "ruim". A qualidade dos dados dos formulários de solicitação de testes para herbívoros não foi devidamente fornecida em casos suspeitos de síndromes neurológicas, apontando para a necessidade de aumentar a conscientização e melhorar o treinamento do pessoal de campo.(AU)


Subject(s)
Animals , Cattle , Rabies/diagnosis , Herbivory , Rabies virus , Signs and Symptoms , Cattle , Animals, Domestic
12.
Ginekol Pol ; 90(9): 544-548, 2019.
Article in English | MEDLINE | ID: mdl-31588553

ABSTRACT

OBJECTIVES: Patients' attitudes and expectations of prenatal screening for genetic abnormalities throughout pregnancy arerarely analyzed by researchers as emotions and fears are both important and challenging factors. Prenatal counselling hasnever been so difficult as we live in the era of detailed ultrasound scans, cell-free fetal DNA and detailed microarray testing.The aim of this study was to investigate Polish women's attitudes towards screening for chromosomal abnormalities andfetal defects. MATERIAL AND METHODS: The study was a prospective survey conducted among a population of Polish women. An electronicquestionnaire regarding prenatal diagnostics was distributed to a total number of 1072 female volunteers. RESULTS: 1044 patients (97.30%) stated that they were motivated to undergo prenatal diagnostics and would want to beinformed about fetal abnormalities. Over 90% of the respondents would want to be informed about serious defects witha high mortality rate (including trisomy 13 or 18). More than half the Polish women (54.83%) stated they were willing toconsider terminating pregnancy in the case of a severe abnormality. CONCLUSIONS: Polish women expect prenatal screening. Almost all Polish women would want to be informed about bothgenetic and anatomical abnormalities and over half of them would consider terminating pregnancy in the case of a severeabnormality. Willingness to learn about a defect increased with average household income, and the statement of a will toterminate pregnancy depended mostly on maternal age and type of fetal abnormality.


Subject(s)
Health Knowledge, Attitudes, Practice/ethnology , Patient Preference , Prenatal Diagnosis , Adult , Female , Humans , Middle Aged , Patient Preference/ethnology , Patient Preference/statistics & numerical data , Poland/ethnology , Pregnancy , Prenatal Diagnosis/psychology , Prenatal Diagnosis/statistics & numerical data , Prospective Studies , Surveys and Questionnaires , Women , Young Adult
13.
Invest New Drugs ; 37(5): 994-1005, 2019 10.
Article in English | MEDLINE | ID: mdl-30661149

ABSTRACT

Thiosemicarbazone is a class of compounds with potential applications in medicine, presenting high capacity to inhibit the growth of cancer cells as well as low toxicity. Because of high interest in anticancer studies involving thiosemicarbazones as new chemotherapeutic agents, a synthetic thiosemicarbazone derivative, 4-N-(2'-methoxy-styryl)-thiosemicarbazone (MTSC) was evaluated in vivo against Ehrlich carcinoma in an animal model. In vivo results demonstrated that MTSC treatment induced the survival of mice and altered significantly the body weight of the surviving mice 12 days after tumor inoculation. Treatment with 30 mg/kg of MTSC exhibited effective cytotoxic activity with T/C values of 150.49% (1 dose) and 278% (2 doses). Its interaction with human serum albumin (HSA), which plays a crucial role in the biodistribution of a wide variety of ligands, was investigated by multiple spectroscopic techniques at 296 K, 303 K, and 310 K, as well as by theoretical calculations. The interaction between HSA and MTSC occurs via ground-state association in the subdomain IIA (Sudlow's site I). The binding is moderate (Ka ≈ 104 M-1), spontaneous, entropically, and enthalpically driven. Molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces. Overall, the interaction HSA:MTSC could provide therapeutic benefits, improving its cytotoxic efficacy and tolerability.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Ehrlich Tumor/pathology , Leukemia, Erythroblastic, Acute/pathology , Serum Albumin, Human/metabolism , Thiosemicarbazones/pharmacology , Animals , Antineoplastic Agents/chemistry , Apoptosis , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/metabolism , Cell Proliferation , Female , Humans , In Vitro Techniques , Leukemia, Erythroblastic, Acute/drug therapy , Leukemia, Erythroblastic, Acute/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Docking Simulation , Protein Binding , Protein Conformation , Serum Albumin, Human/chemistry , Thiosemicarbazones/chemistry , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
14.
RSC Adv ; 9(24): 13386-13397, 2019 Apr 30.
Article in English | MEDLINE | ID: mdl-35519567

ABSTRACT

The photochemical reactivity of the triplet state of pyrano- and furano-1,4-naphthoquinone derivatives (1 and 2) has been examined employing nanosecond laser flash photolysis. The quinone triplets were efficiently quenched by l-tryptophan methyl ester hydrochloride, l-tyrosine methyl ester hydrochloride, N-acetyl-l-tryptophan methyl ester and N-acetyl-l-tyrosine methyl ester, substituted phenols and indole (k q ∼109 L mol-1 s-1). For all these quenchers new transients were formed in the quenching process. These were assigned to the corresponding radical pairs that resulted from a coupled electron/proton transfer from the phenols, indole, amino acids, or their esters, to the excited state of the quinone. The proton coupled electron transfer (PCET) mechanism is supported by experimental rate constants, isotopic effects and theoretical calculations. The calculations revealed differences between the hydrogen abstraction reactions of phenol and indole substrates. For the latter, the calculations indicate that electron transfer and proton transfer occur as discrete steps.

15.
Bioorg Chem ; 81: 79-87, 2018 12.
Article in English | MEDLINE | ID: mdl-30118988

ABSTRACT

A series of N-aryl-2-phenyl-hydrazinecarbothioamides have been investigated as possible inhibitors of tyrosinase, an enzyme involved in the development of melanomas. The hydrazinecarbothioamides 1-6 were synthesized from the reaction between phenylhydrazine and isothiocyanates, for which three different methods have been employed, namely stirring at room temperature, by microwave irradiation or by mechanochemical grinding. Quantitative yields were obtained for the later technique. Compound 4 showed the best value for tyrosinase inhibition (IC50 = 22.6 µM), which occurs through an uncompetitive mechanism. Molecular docking results suggested that 4 can interact via T-stacking with the substrate L-DOPA and via hydrogen bonding and hydrophobic forces with the amino acid residues Ala-79, His-243, Val-247, Phe-263, Val-282, and Glu-321. The interaction between human serum albumin (HSA) and compound 4 occurs through a ground state association and does not perturb the secondary structure of the albumin as well as the microenvironment around Tyr and Trp residues. The binding is spontaneous, moderate and occurs mainly in the Sudlow's site I. Molecular docking results suggested hydrogen bonding, hydrophobic and electrostatic interactions as the main binding forces between the compound 4 and the amino acid residues Lys-198, Trp-214, Glu-449, Leu-452, and Leu-480.


Subject(s)
Enzyme Inhibitors/pharmacology , Hydrazines/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Serum Albumin, Human/antagonists & inhibitors , Thioamides/pharmacology , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Hydrazines/chemical synthesis , Hydrazines/chemistry , Molecular Docking Simulation , Molecular Structure , Monophenol Monooxygenase/metabolism , Serum Albumin, Human/chemistry , Structure-Activity Relationship , Thioamides/chemical synthesis , Thioamides/chemistry
16.
Biomolecules ; 8(3)2018 08 23.
Article in English | MEDLINE | ID: mdl-30142945

ABSTRACT

The interaction between the main carrier of endogenous and exogenous compounds in the human bloodstream (human serum albumin, HSA) and a potential anticancer compound (the capsaicin analogue RPF101) was investigated by spectroscopic techniques (circular dichroism, steady-state, time-resolved, and synchronous fluorescence), zeta potential, and computational method (molecular docking). Steady-state and time-resolved fluorescence experiments indicated an association in the ground state between HSA:RPF101. The interaction is moderate, spontaneous (ΔG° < 0), and entropically driven (ΔS° = 0.573 ± 0.069 kJ/molK). This association does not perturb significantly the potential surface of the protein, as well as the secondary structure of the albumin and the microenvironment around tyrosine and tryptophan residues. Competitive binding studies indicated Sudlow's site I as the main protein pocket and molecular docking results suggested hydrogen bonding and hydrophobic interactions as the main binding forces.


Subject(s)
Capsaicin/chemistry , Capsaicin/metabolism , Molecular Docking Simulation , Serum Albumin, Human/metabolism , Binding, Competitive , Humans , Protein Binding , Protein Conformation , Serum Albumin, Human/chemistry , Spectrum Analysis
17.
Plant Foods Hum Nutr ; 73(3): 222-227, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29982884

ABSTRACT

This study aimed to evaluate the effect of processing steps on bioactive compounds and physicochemical and rheological characteristics of a juçara, banana and strawberry smoothie. The product was obtained by mixing the pulps of these fruits in previously defined proportions. The mixture was standardized in a pilot disintegrator, homogenized at 60 MPa in continuous mode and pasteurized at 90 °C for 35 s. The homogenization step increased the concentration of cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside, major anthocyanins in the smoothie. However, these anthocyanins, as well as perlagonidin-3-O-glucoside, have been reduced (p<0.05) after the pasteurization step. The pasteurization also affected the instrumental color of the smoothie, expressed by Hue angle (p<0.05). Regarding to the rheological behavior, the smoothie, in all processing steps, presented a non-Newtonian fluid behavior with pseudoplastic characteristics (n<1). After homogenization, the smoothie became more fluid and homogeneous. Thus, despite the negative impact of pasteurization on the smoothie's color, the pasteurized product preserves the bioactive compounds such as flavonoids and phenolic acids that are of great importance to human health. Furthermore, the development of this product contributes to add value to the juçara agro-chain and Atlantic Forest preservation.


Subject(s)
Anthocyanins/analysis , Antioxidants/analysis , Euterpe/chemistry , Fragaria/chemistry , Hydroxybenzoates/analysis , Musa/chemistry , Chemical Phenomena , Color , Flavonoids/analysis , Fruit/chemistry , Fruit and Vegetable Juices/analysis , Glucosides/analysis , Pasteurization , Rheology
18.
Eur J Paediatr Neurol ; 22(5): 738-748, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29880258

ABSTRACT

Patients with tuberous sclerosis complex (TSC) are at very high risk for developing epilepsy, and the majority experience seizure onset during the first year of life. Early targeted interventions increase the probability of seizure-freedom and may protect neurodevelopment. In 2012, clinical recommendations for the management of epilepsy in patients with TSC were published by a panel of European experts. Since that time novel studies, reports, and expert opinions in preclinical and clinical TSC-related sciences prompted the need for updated recommendations, including epileptogenesis in TSC, the potential role of predictive biomarkers, the possible benefits of presymptomatic diagnosis and preventive treatment, and new treatment options including mTOR inhibitors. A reconvened panel reviewed the current literature to answer specific questions and five panelists discussed the findings, followed by a general discussion during which all issues were debated to achieve consensus regarding recommendations. A draft manuscript based on these discussions and recommendations was then circulated several times among the panelists, who added their own comments. All the panelists/authors agreed with the final manuscript, which was then submitted for publication. The panel concluded that the need for early diagnosis of TSC-associated seizures is now established, electroencephalographic monitoring has good predictive value for epilepsy before seizure onset in TSC, and, until conclusive data from the EPISTOP trial are available, administration of vigabatrin may be considered in children with subclinical epileptiform EEG discharges. The panel also supported the role of adjunctive everolimus for TSC-associated drug-refractory seizures and emphasized the necessity of early surgical evaluation.


Subject(s)
Epilepsy/etiology , Tuberous Sclerosis/complications , Anticonvulsants , Child , Epilepsy/drug therapy , Epilepsy/prevention & control , Female , Humans , Male
19.
Int J Biol Macromol ; 112: 1062-1072, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29447969

ABSTRACT

A novel series of piperonal mesoionic derivatives (PMI 1-6) was synthesized. Tyrosinase inhibition in the presence of PMI-1, -2, -3, -4, -5 and -6 as well as human serum albumin (HSA) binding studies with PMI-5 and PMI-6 were done by spectroscopic and theoretical methods. The mesoionic compound PMI-5 is the most promising tyrosinase inhibitor with a noncompetitive inhibitory mechanism and an IC50=124µmolL-1. In accordance with the kinetic profile, molecular docking results show that PMI-5 is able to interact favorably with the tyrosinase active site containing the substrate molecule, L-DOPA, interacting with Val-247, Phe-263 and Val-282 residues. The spectroscopic results for the interaction HSA:PMI-5 and HSA:PMI-6 indicated that these mesoionic compounds can associate with HSA in the ground state and energy transfer can occur with high probability. The binding was moderate, spontaneous and can perturb significantly the secondary structure of the albumin. The molecular docking results suggest that PMI-5 and PMI-6 are able to be accommodated inside the Sudlow's site I in HSA, interacting with hydrophobic and hydrophilic amino acid residues.


Subject(s)
Aniline Compounds/chemical synthesis , Aniline Compounds/pharmacology , Benzaldehydes/chemical synthesis , Benzaldehydes/pharmacology , Benzodioxoles/chemical synthesis , Benzodioxoles/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Serum Albumin, Human/metabolism , Aniline Compounds/chemistry , Benzaldehydes/chemistry , Benzodioxoles/chemistry , Binding Sites , Circular Dichroism , Energy Transfer , Humans , Ions , Kinetics , Molecular Docking Simulation , Monophenol Monooxygenase/metabolism , Protein Binding , Protein Structure, Secondary , Serum Albumin, Human/chemistry , Spectrometry, Fluorescence , Thermodynamics
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