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1.
Bol. latinoam. Caribe plantas med. aromát ; 23(4): 523-533, jul. 2024. tab
Artigo em Inglês | LILACS | ID: biblio-1538056

RESUMO

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.


De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.


Assuntos
Animais , Ratos , Extratos Vegetais/administração & dosagem , Croton/química , Inflamação/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Fenóis/análise , Extratos Vegetais/química , Folhas de Planta , Modelos Animais de Doenças , Anti-Inflamatórios/química , Antioxidantes/química
2.
Rev Neurosci ; 35(7): 813-838, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38841811

RESUMO

Glioblastoma multiforme (GBM) exhibits genetic alterations that induce the deregulation of oncogenic pathways, thus promoting metabolic adaptation. The modulation of metabolic enzyme activities is necessary to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates essential for fulfilling the biosynthetic needs of glioma cells. Moreover, the TCA cycle produces intermediates that play important roles in the metabolism of glucose, fatty acids, or non-essential amino acids, and act as signaling molecules associated with the activation of oncogenic pathways, transcriptional changes, and epigenetic modifications. In this review, we aim to explore how dysregulated metabolic enzymes from the TCA cycle and oxidative phosphorylation, along with their metabolites, modulate both catabolic and anabolic metabolic pathways, as well as pro-oncogenic signaling pathways, transcriptional changes, and epigenetic modifications in GBM cells, contributing to the formation, survival, growth, and invasion of glioma cells. Additionally, we discuss promising therapeutic strategies targeting key players in metabolic regulation. Therefore, understanding metabolic reprogramming is necessary to fully comprehend the biology of malignant gliomas and significantly improve patient survival.


Assuntos
Neoplasias Encefálicas , Ciclo do Ácido Cítrico , Glioblastoma , Fosforilação Oxidativa , Humanos , Glioblastoma/metabolismo , Neoplasias Encefálicas/metabolismo , Animais
3.
J Med Food ; 27(8): 758-774, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38910556

RESUMO

Chronic noncommunicable diseases are a global health problem causing increased rates of mortality and sick leaves, which can be reduced by controlling dyslipidemia and hyperglycemia. Experimental and clinical studies have demonstrated the antidiabetic, lipid-lowering, antiobesogenic, anti-inflammatory, and antihypertensive properties of cinnamon; therefore, its use in yogurt can help reverse the effects of these diseases. Our study aims to evaluate the effect of a microencapsulated aqueous extract of cinnamon (Cinnamomum zeylanicum) (MCE Cz) incorporated in a yogurt drink on metabolic syndrome (MS) in a rabbit (Oryctolagus cuniculus). Physicochemical, microbiological, and proximal chemical characterization; total phenol, flavonoid, and 2,2-diphenyl-1-picrylhydrazil activity quantification; intestinal bioaccessibility; sensory analysis; MS induction through diet; and treatment with 5, 10, and 20 mg/kg of flavonoids contained in the MCE Cz were performed to help evaluate morphological, biochemical, and lipid peroxidation measurements in the liver and heart. The results show that the addition of MCE Cz in the yogurt modified the yogurt texture, increased its adhesiveness and firmness, and imparted a characteristic cinnamon color and biological value by providing intestinally bioaccessible antioxidants with antioxidant potential by reducing lipoperoxidation in the liver and heart after treatment. MCE Cz reduced the weight of the animals by up to 38.5% and the abdominal circumference by 29%. Biochemically, it decreased glucose levels by 24.38%, total cholesterol levels by 69.2%, triglyceride levels by 72.69%, and low-density lipoprotein levels by 89.25%; it increased high-density lipoprotein levels by 67.08%. Therefore, adding MCE Cz in doses of 5 and 10 mg of flavonoids in drinkable yogurt can be an alternative to preparing functional foods with physicochemical attributes and biological properties that can be consumed at all stages of life without undesirable effects. Moreover, it can act as a potential adjuvant in the treatment of comorbidities related to MS.


Assuntos
Cinnamomum zeylanicum , Síndrome Metabólica , Extratos Vegetais , Iogurte , Animais , Coelhos , Cinnamomum zeylanicum/química , Síndrome Metabólica/dietoterapia , Iogurte/análise , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Masculino , Alimentos Fortificados/análise , Flavonoides/análise , Flavonoides/administração & dosagem , Composição de Medicamentos , Humanos
4.
Metabolites ; 14(5)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38786726

RESUMO

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations in the hypoxic tumor microenvironment, as well as in transcriptional and signaling networks, which result in changes in global genetic expression. The signaling pathways PI3K/AKT/mTOR and RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, by modulating the transcriptional factors p53, HIF1, and c-Myc. The overexpression of HIF1 and c-Myc, master regulators of cellular metabolism, is a key contributor to the synthesis of bioenergetic molecules that mediate glioma cell transformation, proliferation, survival, migration, and invasion by modifying the transcription levels of key gene groups involved in metabolism. Meanwhile, the tumor-suppressing protein p53, which negatively regulates HIF1 and c-Myc, is often lost in glioblastoma. Alterations in this triad of transcriptional factors induce a metabolic shift in glioma cells that allows them to adapt and survive changes such as mutations, hypoxia, acidosis, the presence of reactive oxygen species, and nutrient deprivation, by modulating the activity and expression of signaling molecules, enzymes, metabolites, transporters, and regulators involved in glycolysis and glutamine metabolism, the pentose phosphate cycle, the tricarboxylic acid cycle, and oxidative phosphorylation, as well as the synthesis and degradation of fatty acids and nucleic acids. This review summarizes our current knowledge on the role of HIF1, c-Myc, and p53 in the genic regulatory network for metabolism in glioma cells, as well as potential therapeutic inhibitors of these factors.

5.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674152

RESUMO

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 µM. These results are promising for potential future therapeutic applications.


Assuntos
Benzimidazóis , Trichomonas vaginalis , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/genética , Trichomonas vaginalis/metabolismo , Benzimidazóis/farmacologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Antiprotozoários/farmacologia , Antitricômonas/farmacologia
6.
Horiz. sanitario (en linea) ; 23(1): 151-158, Jan.-Apr. 2024. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1575013

RESUMO

Resumen Objetivo: Evaluar la eficacia de una intervención familiar en duelo complicado por ruptura de pareja. Materiales y método: Investigación con enfoque mixto de intervención en tres etapas (diagnóstica-implementación-evaluación). En la primera se realizó estudio observacional, transversal, descriptivo, con muestra aleatoria simple con remplazo n=99. Se aplicó "Escala de Distrés por Ruptura Amorosa" de Field y APGAR familiar de Smilkstein, previo consentimiento informado. Se incluyeron cinco familias con duelo complicado y disfunción familiar. Se emplearon métodos y técnicas de trabajo con familia. En la tercera etapa se utilizó diseño cuasi experimental con pretest y postest de duelo complicado y APGAR familiar. Para la captura y análisis de datos se empleó el SPSS V25, con estadística descriptiva y analítica con prueba t de student. Resultados. Fueron mujeres 81.8%, con edad Ⱦ=34,19-29 37.4%, bachillerato 37.4%, separados 59.6%, divorciados 49.4%. Con duelo complicado 14%, disfunción familiar 13%. Las familias con duelo complicado fueron disfuncionales 53.8%. Los factores de riesgo: conflicto en subsistema paterno filial, adicciones, economía. Factores protectores: grupos religiosos, artísticos, educativos y médicos. Las acciones se centraron en intervención cognitivo-conductual-emocional. En evaluación pretest/postest, el duelo complicado presentó diferencia de medias de Ⱦ=8.500, ŝ± 8.925, e IC95%: Li: 3.347 Ls:13.653, con t de student=3.564 y gl=13 y valor de p=0.003, estadísticamente significativo, diferencia de medias para Apgar familiar de Ⱦ= 3.357 con ŝ±1.946, IC95%: Li:2.234, Ls:4.481 con t de student=6.456 y gl=13, valor de p=0.001, estadísticamente significativo. Conclusiones: El efecto de la intervención familiar modificó el duelo complicado y mejoró la dinámica y funcionalidad familiar.


Abstract Objective: To evaluate the effectiveness of a family intervention in grief complicated by a couple breakup. Materials and method: Research with a mixed intervention approach in three stages (diagnosis-implementation-evaluation). In the first, an observational, cross-sectional, descriptive study was carried out, with a simple random sample with replacement n=99. Field's "Romantic Breakup Distress Scale" and Smilkstein's family APGAR were applied, with prior informed consent. Five families with complicated grief and family dysfunction were included. Methods and techniques of working with family were used. In the third stage, a quasi-experimental design was used with pretest and posttest of complicated grief and family APGAR. SPSS V25 was used to capture and analyze data, with descriptive and analytical statistics with Student's t test. Results: They were women 81.8%, with age Ⱦ=34.19-29 37.4%, high school 37.4%, separated 59.6%, divorced 49.4%. With complicated grief 14%, family dysfunction 13%. Families with complicated grief were dysfunctional 53.8%. Risk factors: conflict in paternalfilial subsystem, addictions, economy. Protective factors: religious, artistic, educational and medical groups. The actions focused on cognitive-behavioral-emotional intervention. In pretest/posttest evaluation, complicated grief presented a mean difference of Ⱦ=8.500, ŝ± 8.925, and 95% CI: Li: 3.347 Ls:13.653, with student's t=3.564 and df=13 and p value=0.003, statistically significant, mean difference for family Apgar of Ⱦ= 3.357 with ŝ±1.946, 95% CI: Li:2.234, Ls:4.481 with student's t=6.456 and df=13, p value=0.001, statistically significant. Conclusions: The effect of the family intervention modified complicated grief and improved family dynamics and functionality. Conclusions: The effect of the family intervention modified complicated grief and improved family dynamics and functionality.

7.
Horiz. sanitario (en linea) ; 23(1): 203-210, Jan.-Apr. 2024. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1575018

RESUMO

Resumen Objetivo: Determinar la eficacia del trabajo con familias en fase de duelo complicado por COVID-19, para restablecer la homeostasis y dinámica familiar. Material y Métodos: Estudio con enfoque mixto, bajo un diseño cuasi experimental. Se desarrolló en tres etapas: diagnóstica, intervención y evaluación. En la primera se encuestaron 99 personas que perdieron a un familiar durante la pandemia con el test Inventario de duelo complicado (IDC) y el FF.SIL para estudiar la funcionalidad familiar. Se realizó intervención a cinco familias con duelo complicado y disfunción familiar, mediante trece sesiones presenciales y el empleo de técnicas de terapia narrativa y Gestalt, con la finalidad de recuperar la homeostasis familiar. Para evaluar el efecto de la intervención se aplicó un pos-test, así como los comentarios de las familias. Se realizó prueba t de Student para la diferencia pre y pos-test. Resultados: Se encontraron familias con duelo complicado y disfunción familiar en el 25.3%. En el pretest-postest del FF-SIL, la prueba T de Student observó diferencia de medias de Ⱦ=8.571, desviación estándar de s±7.387, intervalo de confianza de IC95% Li: 4.306; Ls: 12.837 y valor de t= 4.341, gl=13 y valor de p=0.0001, estadísticamente significativo. Conclusión: Con la intervención se logró restablecer la homeostasis, dinámica y salud familiar.


Abstract Objective: To determine the effectiveness of working with families in a phase of grief complicated by COVID-19 to restore homeostasis and family dynamics. Material and Methods: Study with a mixed approach, under a quasi-experimental design. It was developed in three stages: diagnosis, intervention and evaluation. In the first, 99 people who lost a family member during the pandemic were surveyed with the Complicated Grief Inventory (IDC) test and the FF.SIL to study family functionality. An intervention was carried out on five families with complicated grief and family dysfunction, through thirteen face-to-face sessions and the use of narrative and Gestalt therapy techniques, with the aim of recovering family homeostasis. To evaluate the effect of the intervention, a post-test was applied, as well as the families' comments. Student's t test was performed for the pre- and post-test difference. Results: Families with complicated grief and family dysfunction were found in 25.3%. In the pretest-posttest of the FF-SIL, the Student's T test observed a mean difference of Ⱦ=8.571, standard deviation of s±7.387, 95% CI confidence interval Li: 4.306; Ls: 12.837 and t value= 4.341, df=13 and p value=.0001, statistically significant. Conclusion: With the intervention, homeostasis, dynamics and family health were restored.

8.
Clin Transl Oncol ; 26(4): 825-835, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37787973

RESUMO

Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.


Assuntos
Neoplasias Retais , Conduta Expectante , Humanos , Consenso , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Quimiorradioterapia/métodos , Resposta Patológica Completa , Resultado do Tratamento
9.
Int J Mol Sci ; 24(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38139462

RESUMO

Glioma cells exhibit genetic and metabolic alterations that affect the deregulation of several cellular signal transduction pathways, including those related to glucose metabolism. Moreover, oncogenic signaling pathways induce the expression of metabolic genes, increasing the metabolic enzyme activities and thus the critical biosynthetic pathways to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates that are essential to accomplish the biosynthetic needs of glioma cells. In this review, we aim to explore how dysregulated metabolic enzymes and their metabolites from primary metabolism pathways in glioblastoma (GBM) such as glycolysis and glutaminolysis modulate anabolic and catabolic metabolic pathways as well as pro-oncogenic signaling and contribute to the formation, survival, growth, and malignancy of glioma cells. Also, we discuss promising therapeutic strategies by targeting the key players in metabolic regulation. Therefore, the knowledge of metabolic reprogramming is necessary to fully understand the biology of malignant gliomas to improve patient survival significantly.


Assuntos
Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Glutamina/metabolismo , Reprogramação Metabólica , Glicólise/fisiologia , Glioma/patologia , Transdução de Sinais , Apoptose , Proliferação de Células/fisiologia
10.
Nutrients ; 15(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37960203

RESUMO

Hyperammonemia is characterized by the excessive accumulation of ammonia in the body as a result of the loss of liver detoxification, leading to the development of hepatic encephalopathy (HE). These metabolic alterations carry cognitive and motor deficits and cause neuronal damage, with no effective treatment at present. In this study, we aimed to evaluate the effect of two subacute oral administrations of flaxseed oil (0.26 and 0.52 mL/kg) on short- and long-term memory, visuospatial memory, locomotor activity, motor coordination, and the neuronal morphology of the prefrontal cortex (PFC) via tests on Wistar rats with hyperammonemia. The goal was to identify its role in the regulation of cerebral edema, without liver damage causing cerebral failure. In contrast with an ammonium-rich diet, flaxseed oil and normal foods did not cause cognitive impairment or motor alterations, as evidenced in the short-term and visuospatial memory tests. Furthermore, the flaxseed oil treatment maintained a regular neuronal morphology of the prefrontal cortex, which represents a neuroprotective effect. We conclude that the oral administration of flaxseed oil prevents cognitive and motor impairments as well as neuronal alterations in rats with hyperammonemia, which supports the potential use of this oil to ameliorate the changes that occur in hepatic encephalopathy.


Assuntos
Linho , Encefalopatia Hepática , Hiperamonemia , Ratos , Animais , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/prevenção & controle , Encefalopatia Hepática/metabolismo , Ratos Wistar , Óleo de Semente do Linho/farmacologia , Hiperamonemia/complicações , Cognição
11.
Molecules ; 28(22)2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-38005378

RESUMO

A multi-objective optimization was performed using response surface methodology to obtain a high-value-added product, pectin enriched in polyphenols, from pomegranate peel. For this purpose, a green extraction technique that combines citric acid and ultrasound was carried out considering three variables: time, pH, and temperature. The extraction procedure was optimized using the Box-Behnken design, these being the most suitable conditions, with an extraction time of 34.16 min, a pH of 2.2, and a temperature of 89.87 °C. At this point, the pectin yield was 31.89%, with a total retained polyphenol content of 15.84 mg GAE/g pectin. In addition, the water activity, ash content, equivalent weight, methoxyl content, and degree of esterification were determined for the pectin obtained at the optimal point. This study demonstrates that polyphenol-enriched pectin can be obtained from pomegranate peel via an eco-friendly and efficient method, and that it presents similar properties to commercial pectin, preserving its quality and with potential use as an ingredient or food supplement with a high nutritional value. This work contributes to developing sustainable strategies to valorize pomegranate agro-industrial waste and produce high-value functional ingredients.


Assuntos
Pectinas , Punica granatum , Pectinas/química , Polifenóis , Resíduos Industriais , Temperatura
12.
Rev Alerg Mex ; 70(4): 113-120, 2023 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-37933921

RESUMO

Objective: To assess the reproducibility of symptoms in drug challenge tests. Methods: The study included patients with positive cutaneous or challenge test throughout 2019. For each patient, clinical suspicion according to Karch-Lasagna algorithm was registered. Primary outcome was the reproducibility of symptoms in the provocation tests using a paired analysis of data with McNemar test. Results: Eighty-nine patients were included, 16 of them presented more than one positive test. Thirty were skin tests positive and 75 reacted to provocation tests. Eighty nine percent of patients who reacted in challenge test were probably or possibly reactors according to Karch-Lasagna scale. Symptoms of initial reaction did not differ from those triggered in challenge tests. Conclusions: Karch-Lasagna scale is useful in predicting the response to drug provocation tests. In most of the positive studies, results were suggested by clinical history and no differences were found between symptoms triggered in challenge test and that referred to in the previous reaction.


Objetivo: Evaluar la reproducibilidad de los síntomas en pruebas de exposición con fármacos. Métodos: Estudio retrospectivo, efectuado en pacientes con prueba cutánea o exposición positiva, atendidos en 2019. De cada paciente se registró la sospecha clínica según el algoritmo de Karch-Lasagna. El resultado principal fue la reproducibilidad de síntomas en las pruebas de exposición, mediante el análisis de datos emparejado con prueba de McNemar. Resultados: Se incluyeron 89 pacientes, y de estos 16 reportaron varias pruebas positivas. Se obtuvieron 30 pruebas cutáneas y 75 de exposición positivas. En el 89% de las pruebas de exposición positivas, las reacciones iniciales se clasificaron en probables o posibles, según la escala de Karch-Lasagna. Los síntomas reportados en la reacción inicial no difirieron de los de las pruebas de exposición. Conclusiones: La escala de Karch-Lasagna es un método útil para predecir la respuesta en las pruebas de exposición con fármacos. En la mayor parte de las pruebas positivas, los resultados fueron sugeridos por la historia clínica, sin diferencias entre la manifestación de síntomas en la prueba de exposición versus los referidos en la reacción inicial.


Assuntos
Reprodutibilidade dos Testes , Humanos , Testes Cutâneos
13.
Int J Mol Sci ; 24(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37628871

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, affecting an estimated 500 million people worldwide, is a genetic disorder that causes human enzymopathies. Biochemical and genetic studies have identified several variants that produce different ranges of phenotypes; thus, depending on its severity, this enzymopathy is classified from the mildest (Class IV) to the most severe (Class I). Therefore, understanding the correlation between the mutation sites of G6PD and the resulting phenotype greatly enhances the current knowledge of enzymopathies' phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments for patients with G6PD deficiency. In this review, we analyzed and compared the structural and functional data from 21 characterized G6PD variants found in the Mexican population that we previously characterized. In order to contribute to the knowledge regarding the function and structure of the variants associated with G6PD deficiency, this review aimed to determine the molecular basis of G6PD and identify how these mutations could impact the structure, stability, and function of the enzyme and its relation with the clinical manifestations of this disease.


Assuntos
Deficiência de Glucosefosfato Desidrogenase , Glucosefosfato Desidrogenase , Humanos , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Genótipo , Mutação , Fenótipo
14.
Int J Mol Sci ; 24(14)2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37511272

RESUMO

Giardiasis, which is caused by Giardia lamblia infection, is a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs are the main options for controlling infection. Evidence has shown that the nitro drug nitazoxanide (NTZ) is a commonly prescribed treatment for giardiasis; however, the mechanisms underlying NTZ's antigiardial activity are not well-understood. Herein, we identified the glucose-6-phosphate::6-phosphogluconate dehydrogenase (GlG6PD::6PGL) fused enzyme as a nitazoxanide target, as NTZ behaves as a GlG6PD::6PGL catalytic inhibitor. Furthermore, fluorescence assays suggest alterations in the stability of GlG6PD::6PGL protein, whereas the results indicate a loss of catalytic activity due to conformational and folding changes. Molecular docking and dynamic simulation studies suggest a model of NTZ binding on the active site of the G6PD domain and near the structural NADP+ binding site. The findings of this study provide a novel mechanistic basis and strategy for the antigiardial activity of the NTZ drug.


Assuntos
Giardia lamblia , Giardíase , Humanos , Giardíase/tratamento farmacológico , Simulação de Acoplamento Molecular , Tiazóis/farmacologia , Tiazóis/uso terapêutico
15.
PLoS One ; 18(6): e0281385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37384745

RESUMO

The gut microbiota-brain axis is a complex communication network essential for host health. Any long-term disruption can affect higher cognitive functions, or it may even result in several chronic neurological diseases. The type and diversity of nutrients an individual consumes are essential for developing the gut microbiota (GM) and the brain. Hence, dietary patterns might influence networks communication of this axis, especially at the age that both systems go through maturation processes. By implementing Mutual Information and Minimum Spanning Tree (MST); we proposed a novel combination of Machine Learning and Network Theory techniques to study the effect of animal protein and lipid intake on the connectivity of GM and brain cortex activity (BCA) networks in children from 5-to 10 years old from an indigenous community in the southwest of México. Socio-ecological conditions in this nonwestern lifestyle community are very homogeneous among its inhabitants but it shows high individual heterogeneity in the consumption of animal products. Results suggest that MST, the critical backbone of information flow, diminishes under low protein and lipid intake. So, under these nonwestern regimens, deficient animal protein and lipid consumption diets may significantly affect the GM-BCA connectivity in crucial development stages. Finally, MST offers us a metric that unifies biological systems of different nature to evaluate the change in their complexity in the face of environmental pressures or disturbances. Effect of Diet on gut microbiota and brain networks connectivity.


Assuntos
Microbioma Gastrointestinal , Múltiplas Afecções Crônicas , Animais , Humanos , México , Encéfalo , Povos Indígenas , Lipídeos
16.
PhytoKeys ; 225: 83-97, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37252323

RESUMO

Two new species of Harpalyce are described from Cuba, H.revolutasp. nov. from a serpentine area in the northern part of E. Cuba and H.marianensissp. nov. from calcareous areas in the southern part of E. Cuba. Both have relatively small flowers, with an up to 6 mm long standard, and 2-3 mm long wings. Harpalycemarianensis is further characterized by strongly suberous (corky) young branches of a spongy consistence, deeply furrowed longitudinally, and by leaflets covered with a particular type of orange, apparently disk-shaped, sessile glands abaxially. Harpalycerevoluta, moreover, has suborbicular or broadly elliptic leaflets with a strongly recurved or sometimes revolute margin, secondary veins inconspicuous on either side; the foliar glands, by their morphology and anatomy, are of a different type. An epitype is designated for the name Harpalyce and its type, H.formosa; the distribution of both new species and their close relatives is mapped, and an updated identification key is offered, to cater for all 16 currently recognised Cuban species.


ResumenSe describen dos nuevas especies de Harpalyce para Cuba oriental, H.revolutasp. nov. de las áreas de serpentina del norte y H.marianensissp. nov. de áreas de formaciones calcáreas del sur. Ambas se caracterizan por tener flores pequeñas, con estandarte de hasta 6 mm de largo y alas de hasta 3 mm de largo. Harpalycemarianensis se distingue además por sus ramas jóvenes fuertemente suberosas, de consistencia esponjosa, profundamente surcadas longitudinalmente, y los folíolos cubiertos abaxialmente por un tipo particular de glándulas sésiles anaranjadas. Harpalycerevoluta, por su parte, tiene folíolos suborbiculares o anchamente ovales, con margen fuertemente recurvado o hasta revoluto, con venas secundarias inconspicuas en ambas caras, y glándulas foliares, por su morphología y anatomía, son de un tipo distinto. Se designa un epitipo para el nombre Harpalyce y su tipo, H.formosa. Se presenta un mapa de distribución de las nuevas especies y las relacionadas con ellas y se ofrece una clave de identificación actualizada, que incluye las 16 especies cubanas actualmente reconocidas.

17.
Plants (Basel) ; 12(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37111811

RESUMO

Gastric ulcers (GU) constitute a disease with a global prevalence ≈ 8.09 million. Of their causes, non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) rank as the second most frequent etiologic agent. The pathogenic process of gastric lesions is given by the overproduction of oxidative stress, promotion of inflammatory processes, and inhibition of prostaglandin synthesis. Spirulina Arthrospira maxima (SP) is a cyanobacterium with a wide variety of substances with high nutritional and health values such as phycobiliproteins (PBPs) that have outstanding antioxidant activity, anti-inflammatories effects, and accelerate the wound healing process. This study aimed to determine the protective effect of PBPs in GU induced by IND 40 mg/kg. Our results show that the PBPs protected against IND-induced damage with a dose-dependent effect. At a dose of 400 mg/kg, a marked decrease in the number of lesions is observed, as well as the recovery of the main markers of oxidative stress damage (MDA) and antioxidant species (SOD, CAT, GPx) at close to baseline levels. The evidence derived from the present investigation suggests that the antioxidant effect of PBPs, together with their reported anti-inflammatory effects to accelerate the wound healing process, is the most reliable cause of their antiulcerogenic activity in this GU model.

18.
Microorganisms ; 11(3)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36985142

RESUMO

Laccases are valuable enzymes as an excellent ecological alternative for bioremediation issues because they can oxidize persistent xenobiotic compounds. The production and characterization of extracellular laccases from saprotrophic fungi from disturbed environments have been scarcely explored, even though this could diversify their functional characteristics and expand the conditions in which they carry out their catalysis. Agrocybe pediades, isolated from a disturbed forest, produces an extracellular laccase in liquid culture. The enzyme was purified, identified and characterized. Copper and hexachlorobenzene do not function as inducers for the laccase produced. Partial amino acid sequences were obtained by LC-MS/MS that share similarity with laccases from other fungi. Purified laccase is a monomer with a molecular mass between 55-60 kDa and had an optimum activity at pH 5.0 and the optimum temperature at 45 °C using 2,6-dimethoxyphenol (2,6-DMP) as substrate. The Km and Vmax also determined with 2,6-DMP were 100 µM and 285 µmol∙min-1∙mg-1, respectively, showing that the laccase of A. pediades has a higher affinity for this substrate than that of other Agaricales. These features could provide a potential catalyst for different toxic substrates and in the future laccase could be used in environmental recovery processes.

19.
Plants (Basel) ; 12(4)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36840070

RESUMO

Arthrospira (Spirulina) maxima (SM) is a cyanobacterium that has a long history of being used as human food. In recent years, several investigations have shown its beneficial biological effects, among which its antioxidant capacity has been highlighted. The purpose of this study was to evaluate the effects of SM on body weight, glycemia, sexual behavior, sperm quality, testosterone levels, sex organ weights, and the activity of antioxidant enzymes in diabetic male rats (a disease characterized by an increase in reactive oxygen species). The experiment consisted of six groups of sexually expert adult males (n = 6): (1) control (vehicle); (2) streptozotocin (STZ)-65 mg/kg; (3) SM-400 mg/kg; (4) STZ + SM-100 mg/kg; (5) STZ + SM-200 mg/kg; and (6) STZ + SM-400 mg/kg. Sexual behavior tests were performed during the first 3 h of the dark period under dim red illumination. Our results showed that SM significantly improved sexual behavior and sperm quality vs. diabetic animals. Likewise, while the enzymatic activities of SOD and GPx increased, TBARS lipoperoxidation decreased and testosterone levels increased. In view of the findings, it is suggested that SM may potentially be used as a nutraceutical for the treatment of diabetic male sexual dysfunction due to its antioxidant property.

20.
Molecules ; 27(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36558035

RESUMO

Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H2N-BZM6, O2N-BZM7, and O2N-BZM9. The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds (O2N-BZM7 and O2N-BZM9), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.


Assuntos
Antiprotozoários , Giardia lamblia , Parasitos , Trichomonas vaginalis , Animais , Humanos , Metronidazol/farmacologia , Antiparasitários/farmacologia , Benzimidazóis/farmacologia , Antiprotozoários/farmacologia
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