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1.
Nanomaterials (Basel) ; 14(6)2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38535691

ABSTRACT

Second-generation thin-film Cu(In, Ga)Se2 (CIGS) solar cells are a well-established photovoltaic technology with a record power conversion efficiency of 23.6%. However, their reliance on critical raw materials, such as In and Ga, requires new approaches to reduce the amount of critical raw materials employed. The micro-concentrator concept involves the combination of thin-film photovoltaic technology with concentrator photovoltaic technology. This approach reduces the size of the solar cell to the micrometer range and uses optical concentration to collect sunlight from a larger area, focusing it onto micro solar cells. This work is devoted to the development of a process for manufacturing pre-structured substrates with regular arrays of holes with 200 and 250 µm diameters inside a SiOx insulating matrix. Subsequently, a Cu-In-Ga precursor is deposited by sputtering, followed by photoresist lift-off and the application of a Cu-In-Ga thermal annealing at 500 °C to improve precursor quality and assess pre-structured substrate stability under elevated temperatures. Finally, a two-stage selenization process leads to the formation of CIGS absorber micro-dots. This study presents in detail the fabrication process and explores the feasibility of a bottom-up approach using pre-structured substrates, addressing challenges encountered during fabrication and providing insights for future improvements in CIGS absorber materials.

2.
Metabolites ; 14(1)2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38248839

ABSTRACT

This review article compiles critical pre-analytical factors for sample collection and extraction of eight uncommon or underexplored biological specimens (human breast milk, ocular fluids, sebum, seminal plasma, sweat, hair, saliva, and cerebrospinal fluid) under the perspective of clinical metabolomics. These samples are interesting for metabolomics studies as they reflect the status of living organisms and can be applied for diagnostic purposes and biomarker discovery. Pre-collection and collection procedures are critical, requiring protocols to be standardized to avoid contamination and bias. Such procedures must consider cleaning the collection area, sample stimulation, diet, and food and drug intake, among other factors that impact the lack of homogeneity of the sample group. Precipitation of proteins and removal of salts and cell debris are the most used sample preparation procedures. This review intends to provide a global view of the practical aspects that most impact results, serving as a starting point for the designing of metabolomic experiments.

3.
Pediatr Nephrol ; 39(4): 1245-1251, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37796325

ABSTRACT

BACKGROUND: The main objective was to test whether the Renal Angina Index (RAI), calculated on patient admission to the pediatric intensive care unit (PICU), is associated with the risk of acute kidney injury (AKI) based on the Kidney Disease: Improving Global Outcomes (KDIGO) (stage ≥ 2) in 72 h. The specific aim was to analyze the performance of the RAI at a specialized oncology PICU. METHODS: Retrospective cohort study involving two pediatric intensive care units located within a general hospital and an oncology hospital. Children aged ≥ 3 months to < 18 years admitted to the intensive care units in 2017 with a length of stay ≥ 72 h were included. RESULTS: The sample included 249 patients, of which 51% were male (127 patients), with median age of 77 months, and mean ICU stay of 5 days. Of the total admissions, 141 were clinical (57%) and 108 surgical. The rate of AKI was 15% and death rate within 30 days was 13%. Having a positive RAI on admission showed a statistically significant association with AKI at Day 3 (OR = 18.5, 95%CI = 4.3 - 78.9, p < 0.001) and with death (OR = 3.9, 95%CI = 1.6 - 9.9, p = 0.004). The accuracy of the RAI in the cancer population was 0.81 on the ROC curve (95%CI 0.74, 0.88). CONCLUSIONS: The RAI is a useful tool for predicting AKI and death in critically ill children, including in oncology units.


Subject(s)
Acute Kidney Injury , Critical Illness , Child , Humans , Male , Female , Retrospective Studies , Prospective Studies , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/epidemiology , Intensive Care Units, Pediatric
4.
Cureus ; 15(9): e45527, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37868390

ABSTRACT

Budd-Chiari syndrome (BCS) is a rare condition characterized by the obstruction of hepatic venous outflow. It has various potential etiologies, with myeloproliferative neoplasms representing the most prevalent pathogenic association. Here, we present the case of a 51-year-old male who manifested abdominal pain and ascites. Subsequent clinical investigation revealed the presence of BCS secondary to a myeloproliferative syndrome, specifically polycythemia vera. This case emphasizes the importance of diagnosing BCS and conducting a thorough investigation into its underlying etiology.

5.
Nanomaterials (Basel) ; 13(15)2023 Aug 05.
Article in English | MEDLINE | ID: mdl-37570574

ABSTRACT

The fabrication of Sb2Se3 thin-film solar cells deposited by a pulsed hybrid reactive magnetron sputtering (PHRMS) was proposed and examined for different growth conditions. The influence of growth temperature and Se pulse period were studied in terms of morphology, crystal structure, and composition. The Sb2Se3 growth showed to be dependent on the growth temperature, with a larger crystal size for growth at 270 °C. By controlling the Se pulse period, the crystal structure and crystal size could be modified as a function of the supplied Se amount. The solar cell performance for Sb2Se3 absorbers deposited at various temperatures, Se pulse periods and thicknesses were assessed through current-voltage characteristics. A power conversion efficiency (PCE) of 3.7% was achieved for a Sb2Se3 solar cell with 900 nm thickness, Sb2Se3 deposited at 270 °C and Se pulses with 0.1 s duration and period of 0.5 s. Finally, annealing the complete solar cell at 100 °C led to a further improvement of the Voc, leading to a PCE of 3.8%, slightly higher than the best reported Sb2Se3 solar cell prepared by sputtering without post-selenization.

6.
Cureus ; 15(3): e36804, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37123740

ABSTRACT

A low blood glucose level (less than 55 mg/dL) associated with autonomic and neuroglycopenic signs and symptoms that resolve after glucose administration establishes Whipple's triad, indicating the presence of a hypoglycemic disorder. Insulinoma remains the most common cause of endogenous hyperinsulinemia. We present the case of a 73-year-old male who was brought to the emergency department after losing consciousness. On initial assessment, severe hypoglycemia was identified and treated. No abnormalities were detected on the physical examination, initial blood tests, abdominal ultrasound and computed tomography (CT) thorax, and abdomen and pelvis. The patient had another episode of symptomatic hypoglycemia, and the blood tests performed were compatible with endogenous hyperinsulinism. The patient was started on diazoxide to prevent further hypoglycemia episodes. Magnetic resonance imaging (MRI) showed a nodular area in the cephalic region of the pancreas, and the patient was discharged with diazoxide and flash glucose monitoring. In the follow-up appointment, he presented with signs and symptoms of congestive heart failure. Endoscopic ultrasound was requested, but the patient was at high risk for complications while undergoing the procedure under anesthesia due to congestive heart failure. A 68Gallium-DOTA-NOC positron emission tomography and computed tomography (PET-CT) was requested and confirmed the presence of a nodular area in the cephalic region of the pancreas. He was referred to general surgery for definitive treatment. Insulinoma is still a challenging medical condition. Therefore, management by a multidisciplinary team is essential. This case highlights the impact that side effects of medication used to treat this condition can have. Diazoxide was initiated to stop severe recurrent hypoglycemia; however, the patient developed congestive heart failure and was unable to undergo an endoscopic ultrasound to localize the lesion, resulting in a delay in diagnosis and definitive treatment. Diazoxide is a potent hyperglycemic drug but it can also cause fluid retention, nausea, hypertrichosis, neutropenia, and thrombocytopenia.

7.
Metabolites ; 13(3)2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36984795

ABSTRACT

Current evidence suggests that gut microbiome-derived lipids play a crucial role in the regulation of host lipid metabolism. However, not much is known about the dynamics of gut microbial lipids within the distinct gut biogeographic. Here we applied targeted and untargeted lipidomics to in vitro-derived feces. Simulated intestinal chyme was collected from in vitro gut vessels (V1-V4), representing proximal to distal parts of the colon after 24 and 48 h with/without polydextrose treatment. In total, 44 simulated chyme samples were collected from the in vitro colon simulator. Factor analysis showed that vessel and time had the strongest impact on the simulated intestinal chyme lipid profiles. We found that levels of phosphatidylcholines, sphingomyelins, triacylglycerols, and endocannabinoids were altered in at least one vessel (V1-V4) during simulation. We also found that concentrations of triacylglycerols, diacylglycerols, and endocannabinoids changed with time (24 vs. 48 h of simulation). Together, we found that the simulated intestinal chyme revealed a wide range of lipids that remained altered in different compartments of the human colon model over time.

8.
Integr Zool ; 18(3): 518-529, 2023 May.
Article in English | MEDLINE | ID: mdl-35275446

ABSTRACT

Chemical profiles of non-invasive biological material, such as feces, have great potential to study elusive animals or those with low population densities. Here, we use a metabolomic approach to evaluate Neotropical mustelids as a biological model to describe the diversity of the metabolites present in fecal samples, as well as to evaluate the potential of chemical profiles for taxonomic discrimination. We collected fecal samples from captive individuals of 5 species of mustelids occurring in Brazil and analyzed them by liquid chromatography coupled to high-resolution mass spectrometry. Over 200 compounds have been annotated; "bile acids, alcohols and derivatives" was the most expressive class in the metabolome of all the species. We successfully discriminated 3 taxonomic groups: 1-tayra (Eira barbara); 2-otters (Lontra longicaudis and Pteronura brasiliensis; 1); and 3-grisons (Galictis vittata and Galictis cuja). Several compounds seemed to be associated with food intake and the digestive process, while others were found for the first time in Neotropical mustelids. We concluded that mustelids show high metabolome diversity and that species-specific identification through metabolomic profiles is possible, thus contributing to the development and implementation of additional non-invasive approaches in the study of mustelids.


Subject(s)
Otters , Animals , Metabolome , Feces/chemistry , Brazil/epidemiology , Metabolomics/methods
9.
Cell Rep Med ; 3(10): 100762, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36195095

ABSTRACT

The gut microbiota is crucial in the regulation of bile acid (BA) metabolism. However, not much is known about the regulation of BAs during progression to type 1 diabetes (T1D). Here, we analyzed serum and stool BAs in longitudinal samples collected at 3, 6, 12, 18, 24, and 36 months of age from children who developed a single islet autoantibody (AAb) (P1Ab; n = 23) or multiple islet AAbs (P2Ab; n = 13) and controls (CTRs; n = 38) who remained AAb negative. We also analyzed the stool microbiome in a subgroup of these children. Factor analysis showed that age had the strongest impact on both BA and microbiome profiles. We found that at an early age, systemic BAs and microbial secondary BA pathways were altered in the P2Ab group compared with the P1Ab and CTR groups. Our findings thus suggest that dysregulated BA metabolism in early life may contribute to the risk and pathogenesis of T1D.


Subject(s)
Diabetes Mellitus, Type 1 , Islets of Langerhans , Child , Humans , Autoimmunity , Islets of Langerhans/chemistry , Autoantibodies/analysis , Bile Acids and Salts
10.
Anal Chim Acta ; 1232: 340469, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36257759

ABSTRACT

Several areas such as microbiology, botany, and medicine use genetic information and computational tools to organize, classify and analyze data. However, only recently has it been possible to obtain the chemical ontology of metabolites computationally. The systematic classification of metabolites into classes opens the way for adapting methods that previously used genetic taxonomy to now accept chemical ontology. Community ecology tools are ideal for this adaptation as they have mature methods and enable exploratory data analysis with established statistical tools. This study introduces the Metabology approach, which transforms metabolites into an ecosystem where the metabolites (species) are related by chemical ontology. In the present work, we demonstrate the applicability of this new approach using publicly available data from a metabolomics study of human plasma that searched for prognostic markers of COVID-19, and in an untargeted metabolomics study carried out by our laboratory using Lasiodiplodia theobromae fungal pathogen supernatants.


Subject(s)
COVID-19 , Ecosystem , Humans , Metabolomics/methods
11.
Bioorg Med Chem ; 71: 116952, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35930852

ABSTRACT

The search for new drug candidates against Alzheimer's disease (AD) remains a complex challenge for medicinal chemists due to its multifactorial pathogenesis and incompletely understood physiopathology. In this context, we have explored the molecular hybridization of pharmacophore structural fragments from known bioactive molecules, aiming to obtain a novel molecular architecture in new chemical entities capable of concomitantly interacting with multiple targets in a so-called multi-target directed ligands (MTDLs) approach. This work describes the synthesis of 4-hydroxymethyl)piperidine-N-benzyl-acyl-hydrazone derivatives 5a-l, designed as novel MTDLs, showing improved multifunctional properties compared to the previously reported parent series of N-benzyl-(3-hydroxy)piperidine-acyl-hydrazone derivatives 4. The new improved derivatives were studied in silico, regarding their mode of interaction with AChE enzyme, and in vitro, for evaluation of their effects on the selective inhibition of cholinesterases, cellular antioxidant, and neuroprotective activities as their cytotoxicity in human neuroblastoma (SH-SY5Y) cells. Overall, compound PQM-181 (5 k) showed the best balanced selective and non-competitive inhibition of AChE (IC50 = 5.9 µM, SI > 5.1), with an additional antioxidant activity (IC50 = 7.45 µM) against neuronal t-BOOH-induced oxidative stress and neuroprotective ability against neurotoxicity elicited by both t-BOOH and OAß1-42, and a moderate ability to interfere in Aß1-42 aggregates, with low cytotoxicity and good predictive druggability properties, suggesting a multifunctional pharmacological profile suitable for further drug development against AD.


Subject(s)
Alzheimer Disease , Neuroblastoma , Neuroprotective Agents , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amyloid beta-Peptides , Antioxidants/pharmacology , Cholinesterase Inhibitors/chemistry , Drug Design , Humans , Hydrazones/pharmacology , Hydrazones/therapeutic use , Ligands , Molecular Structure , Neuroblastoma/drug therapy , Neuroprotective Agents/chemistry , Piperidines/chemistry , Structure-Activity Relationship
12.
Int Immunopharmacol ; 110: 108952, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35716482

ABSTRACT

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum (L. infantum). Currently, there are no vaccines and/or prophylactic therapies against VL, and the recentpharmacological approaches come from the drug repositioning strategy. Here, we evaluated the anticancer drug pamidronate (PAM) to identify a new therapeutic option for the treatment of human VL. We assessed its in vitro antileishmanial activity against the promastigote and amastigote forms of L. infantum by evaluating cell cytotoxicity. The antileishmanial and immunomodulatory activities were assessed using human peripheral blood leukocytes ex vivo. PAM induced the formation of vacuoles in the cytoplasm of the promastigotes and alterations in the morphology of the kinetoplast and mitochondria in vitro, which indicates anti-promastigote activity. PAM also reduced the number of infected macrophages and intracellular amastigotes in a concentration-dependent manner, with cell viability above 70%. In ex vivo, PAM reduced the internalized forms of L. infantum in the classical monocyte subpopulation. Furthermore, it enhanced IL-12 and decreased IL-10 and TGF-ß by monocytes and neutrophils. Increased IFN-γ and TNF levels for CD8- and CD8+ T lymphocytes and B lymphocytes, respectively, were observed after the treatment with PAM, as well as a reduction in IL-10 by the lymphocyte subpopulations evaluated. Taken together, our results suggest that PAM may be eligible as a potential therapeutic alternative for drug repurposing to treat human visceral leishmaniasis.


Subject(s)
Antiprotozoal Agents , Leishmania infantum , Leishmaniasis, Visceral , Leishmaniasis , Animals , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Drug Repositioning , Humans , Interleukin-10/therapeutic use , Leishmaniasis/drug therapy , Leishmaniasis, Visceral/drug therapy , Mice , Mice, Inbred BALB C , Pamidronate
13.
PLoS One ; 17(6): e0269447, 2022.
Article in English | MEDLINE | ID: mdl-35666748

ABSTRACT

Leishmaniasis is a public health issue. It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. LASSBio-1736 was described as antileishmanial drug-candidate to cutaneous leishmaniasis, displaying plasma stability and with no preliminary signals of hepatic or renal toxicity. In this paper, we described the in vitro pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is in vitro and in vivo leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low in vitro systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed in vitro and in vivo. It exhibited no cytotoxic effect to mammalian cells and displayed good in -vivo effect against BALB/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime.


Subject(s)
Antiprotozoal Agents , Leishmania major , Leishmaniasis, Cutaneous , Animals , Antiprotozoal Agents/pharmacokinetics , Antiprotozoal Agents/therapeutic use , Leishmaniasis, Cutaneous/drug therapy , Mammals , Mice , Mice, Inbred BALB C , Neglected Diseases/drug therapy
14.
Psicol. ciênc. prof ; 42: e240111, 2022. tab
Article in Portuguese | LILACS, Index Psychology - journals | ID: biblio-1422374

ABSTRACT

Este trabalho tem por objetivo problematizar o agenciamento entre a psicologia e o aparelho judiciário. Para tanto, tomamos a escala Psychopathy Checklist Revised (PCL-R) - criada por Robert Hare para avaliar e mensurar a psicopatia - como um acontecimento analisador. Realizamos uma pesquisa de natureza qualitativa que fez uso da pesquisa bibliográfica e documental como estratégias metodológicas. Os dados produzidos foram analisados à luz das obras de Foucault e de autores da criminologia crítica. Pensamos a psicologia e o aparelho judiciário como marcados por lógicas normativas que produzem práticas de controle sobre os modos de existir. Por este viés, ao se agenciar com dispositivos do sistema penal, determinadas práticas psi podem instrumentalizar os artefatos de controle e repressão. Em nosso percurso de pesquisa, realizamos uma revisão de literatura da produção acadêmica brasileira relativa à utilização da escala no país (2005-2018). Partindo da análise das publicações encontradas constatou-se que a maioria das pesquisas enfatizam as propriedades psicométricas da escala e reforçam a sua eficácia em predizer a reincidência criminal. Ademais, verificou-se que as publicações levantadas não analisam as implicações ético-políticas da aplicação da escala na execução penal, assim como não consideram a instituição prisional como produtora e mantenedora da delinquência. Por fim, questionamos se a escala PCL-R seria utilizada como mais um dispositivo de controle e gestão da vida das populações que são alvo do sistema penal brasileiro.(AU)


This essay aims to problematize the agency between Psychology and the court system. For this purpose, we take the Psychopathy Checklist Revised scale (PCL-R ) - created by Robert Hare to assess and measure psychopathy - as an analyzer event. We conducted a qualitative research that used bibliographic and documentary research as methodological strategies. The data produced were analyzed considering the works of Foucault and authors of critical criminology. We think psychology and the judiciary as marked by normative logics that produce control practices over the ways of existence. By this perspective, when used with devices of the penal system, certain psychological practices instrumentalize the artifacts of control and repression. In our research course, we conducted a literature review of the Brazilian academic production related to use of the scale in the country (2005-2018). Based on the analysis of the publications found, most studies emphasize the psychometric properties of the scale and reinforce its alleged effectiveness in predicting criminal recidivism. Moreover, we verified that the publications do not analyze the ethical-political implications that applying the scale produces in criminal execution, and disregards the prison institution as a producer of delinquency. Finally, we questioned if the PCL-R scale was used more as a device for controlling and administering the lives of populations that are targets of the prison system.(AU)


Este trabajo tiene como objetivo problematizar la agencia entre la psicología y el poder judicial. Para eso, tomamos la Escala Psychopathy Checklist Revised (PCL-R), creada por Robert Hare para evaluar y medir la psicopatía, como un "evento analítico". Realizamos una investigación cualitativa que hizo uso de la investigación bibliográfica y documental como estrategias metodológicas. Los datos producidos se analizaron a raíz de los trabajos de Foucault y autores de criminología crítica. Pensamos en la psicología y en el poder judicial como marcados por lógicas normativas que producen prácticas de control sobre las formas de existir. Debido a este sesgo, cuando se trata con dispositivos del sistema penal, ciertas prácticas "psi" instrumentalizan los artefactos de control y represión. En nuestro camino de investigación, realizamos una revisión de la literatura de la producción académica brasileña con respecto al uso de la escala en el país (2005-2018). Según el análisis de las publicaciones encontradas, se descubrió que la mayoría de los estudios enfatizan las propiedades psicométricas de la Escala y refuerzan su efectividad para predecir la recurrencia criminal. Además, se encontró que las publicaciones planteadas no analizaron las implicaciones ético-políticas que la aplicación de la Escala produce en la ejecución criminal, ni consideraron a la institución penitenciaria como productora y mantenedora de la delincuencia. Finalmente, nos preguntamos si la Escala PCL-R se usaría como otro dispositivo para controlar y administrar las vidas de las poblaciones que son objetivo del sistema penal brasileño.(AU)


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Brief Psychiatric Rating Scale , Prisons , Judiciary , Forensic Psychology , Human Rights , Antisocial Personality Disorder , Anxiety , Pain , Psychology , Psychometrics , Psychopathology , Punishment , Social Isolation , Violence , Conscience , Criminology , Aggression , Diagnosis , Ethics , Apathy , Recidivism , Freedom , Homicide , Morale
15.
Cell Rep ; 37(6): 109973, 2021 11 09.
Article in English | MEDLINE | ID: mdl-34758307

ABSTRACT

T cell activation, proliferation, and differentiation involve metabolic reprogramming resulting from the interplay of genes, proteins, and metabolites. Here, we aim to understand the metabolic pathways involved in the activation and functional differentiation of human CD4+ T cell subsets (T helper [Th]1, Th2, Th17, and induced regulatory T [iTreg] cells). Here, we combine genome-scale metabolic modeling, gene expression data, and targeted and non-targeted lipidomics experiments, together with in vitro gene knockdown experiments, and show that human CD4+ T cells undergo specific metabolic changes during activation and functional differentiation. In addition, we confirm the importance of ceramide and glycosphingolipid biosynthesis pathways in Th17 differentiation and effector functions. Through in vitro gene knockdown experiments, we substantiate the requirement of serine palmitoyltransferase (SPT), a de novo sphingolipid pathway in the expression of proinflammatory cytokines (interleukin [IL]-17A and IL17F) by Th17 cells. Our findings provide a comprehensive resource for selective manipulation of CD4+ T cells under disease conditions characterized by an imbalance of Th17/natural Treg (nTreg) cells.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cell Differentiation , Ceramides/metabolism , Glycosphingolipids/metabolism , Metabolome , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , CD4-Positive T-Lymphocytes/metabolism , Genome, Human , Humans , Lymphocyte Activation , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
16.
ACS Med Chem Lett ; 12(9): 1405-1412, 2021 Sep 09.
Article in English | MEDLINE | ID: mdl-34531949

ABSTRACT

5-Nitro-furan nitrones (1) and 5-nitro-thiophene nitrones (2) were synthesized in one step. Compounds 1a-c had the most potent leishmanicidal activity against intracellular amastigote forms of Leishmania amazonensis and L. infantum (from 0.019 to 2.76 µM), with excellent selectivity (from 39 to 5673). The comparison of the leishmanicidal activity in promastigotes of wild type L. donovani with those overexpressing nitroreductases NRT1 or NRT2 shows that 1a,b are activated by both, which could slow the development of resistance. Their redox potential (E redox) obtained by cyclic voltammetry (-0.67 and -0.62 V) shows that the reduction of the nitro group is modulated by the nitrone group. Oral administration of 1b to mice infected by L. infantum reduced the parasite load on the spleen by 76.6 and 95.0% with doses of 50 and 100 mg/kg, respectively, administered twice a day, for 5 days. In the liver, the parasite load suppression was above 75% with either treatment.

17.
Metabolites ; 11(1)2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33467644

ABSTRACT

Various studies aiming to elucidate the role of the gut microbiome-metabolome co-axis in health and disease have primarily focused on water-soluble polar metabolites, whilst non-polar microbial lipids have received less attention. The concept of microbiota-dependent lipid biotransformation is over a century old. However, only recently, several studies have shown how microbial lipids alter intestinal and circulating lipid concentrations in the host, thus impacting human lipid homeostasis. There is emerging evidence that gut microbial communities play a particularly significant role in the regulation of host cholesterol and sphingolipid homeostasis. Here, we review and discuss recent research focusing on microbe-host-lipid co-metabolism. We also discuss the interplay of human gut microbiota and molecular lipids entering host systemic circulation, and its role in health and disease.

18.
Article in English | MEDLINE | ID: mdl-33278596

ABSTRACT

Lipids have many important biological roles, such as energy storage sources, structural components of plasma membranes and as intermediates in metabolic and signaling pathways. Lipid metabolism is under tight homeostatic control, exhibiting spatial and dynamic complexity at multiple levels. Consequently, lipid-related disturbances play important roles in the pathogenesis of most of the common diseases. Lipidomics, defined as the study of lipidomes in biological systems, has emerged as a rapidly-growing field. Due to the chemical and functional diversity of lipids, the application of a systems biology approach is essential if one is to address lipid functionality at different physiological levels. In parallel with analytical advances to measure lipids in biological matrices, the field of computational lipidomics has been rapidly advancing, enabling modeling of lipidomes in their pathway, spatial and dynamic contexts. This review focuses on recent progress in systems biology approaches to study lipids in health and disease, with specific emphasis on methodological advances and biomedical applications.


Subject(s)
Biomedical Research/methods , Lipid Metabolism/physiology , Lipidomics/methods , Systems Biology/methods , Biomedical Research/trends , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/therapy , Humans , Lipid Metabolism/drug effects , Lipidomics/trends , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/therapy , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/therapy , Obesity/diagnosis , Obesity/metabolism , Obesity/therapy , Psychotic Disorders/diagnosis , Psychotic Disorders/metabolism , Psychotic Disorders/therapy , Systems Biology/trends
19.
Front Med (Lausanne) ; 7: 275, 2020.
Article in English | MEDLINE | ID: mdl-32656216

ABSTRACT

Continuous climate changes associated with the disorderly occupation of urban areas have exposed Latin American populations to the emergence and reemergence of arboviruses transmitted by Aedes aegypti. The magnitude of the financial and political problems these epidemics may bring to the future of developing countries is still ignored. Due to the lack of effective antiviral drugs and vaccines against arboviruses, the primary measure for preventing or reducing the transmission of diseases depends entirely on the control of vectors or the interruption of human-vector contact. In Brazil the first attempt to control A. aegypti took place in 1902 by eliminating artificial sites of eproduction. Other strategies, such as the use of oviposition traps and chemical control with dichlorodiphenyltrichlorethane and pyrethroids, were successful, but only for a limited time. More recently, biotechnical approaches, such as the release of transgenics or sterile mosquitoes and the, development of transmission blocking vaccines, are being applied to try to control the A. aegypti population and/or arbovirus transmission. Endemic countries spend about twice as much to treat patients as they do on the prevention of mosquito-transmitted diseases. The result of this strategy is an explosive outbreak of arboviruses cases. This review summarizes the social impacts caused by A. aegypti-transmitted diseases, mainly from a biotechnological perspective in vector control aimed at protecting Latin American populations against arboviruses.

20.
J Pineal Res ; 69(3): e12685, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32702775

ABSTRACT

Melatonin and its indoles derivatives are central in the synchronization of malaria parasites. In this research, we discovered that melatonin is unable to increase the parasitemia in the human malaria Plasmodium falciparum that lacks the kinase PfeIK1. The PfeIK1 knockout strain is a valuable tool in the screening of indol-related compound that blocks the melatonin effect in wild-type (WT) parasite development. The assays were performed by using flow cytometry with simultaneous labeling for mitochondria viability with MitoTracker Deep Red and nucleus staining with SYBR Green. We found that Melatotosil leads to an increase in parasitemia in P. falciparum and blocks melatonin effect in the WT parasite. Using microscopy imaging system, we found that Melatotosil at 500 nM is able to induce cytosolic calcium rise in transgenic PfGCaMP3 parasites. On the contrary, the compound Triptiofen blocks P. falciparum cell cycle with IC50 9.76 µM ± 0.6, inhibits melatonin action, and does not lead to a cytosolic calcium rise in PfGCaMP3 parasites. We also found that the synthetic indol-related compounds arrested parasite cycle for PfeIK1 knockout and (WT) P. falciparum (3D7) in 72 hours culture assays with the IC50 values slighting lower for the WT strain. We concluded that the kinase PfeIK1 is central for melatonin downstream signaling pathways involved in parasite cell cycle progression. More importantly, the indol-related compounds block its cycle as an upstream essential mechanism for parasite survival. Our data clearly show that this class of compounds emerge as an alternative for the problem of resistance with the classical antimalarials.


Subject(s)
Antimalarials/pharmacology , Cell Cycle , Malaria, Falciparum/enzymology , Plasmodium falciparum/enzymology , Signal Transduction , ets-Domain Protein Elk-1/antagonists & inhibitors , Antimalarials/chemistry , Humans , Malaria, Falciparum/drug therapy , Melatonin , ets-Domain Protein Elk-1/metabolism
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