Effect of Supplementation with Omega-3 Polyunsaturated Fatty Acids on Metabolic Modulators in Skeletal Muscle of Rats with an Obesogenic High-Fat Diet.

Previous studies provided evidence of the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on the cardiovascular system and inflammation. However, its possible effect on skeletal muscle is unknown. This study aimed to evaluate whether ω-3 PUFA reverses the dysregulation of metabolic modulators in the skeletal muscle of rats on a high-fat obesogenic diet. For this purpose, an animal model was developed using male Wistar rats with a high-fat diet (HFD) and subsequently supplemented with ω-3 PUFA. Insulin resistance was assessed, and gene and protein expression of metabolism modulators in skeletal muscle was also calculated using PCR-RT and Western blot. Our results confirmed that in HFD rats, zoometric parameters and insulin resistance were increased compared to SD rats. Furthermore, we demonstrate reduced gene and protein expression of peroxisome proliferator-activated receptors (PPARs) and insulin signaling molecules. After ω-3 PUFA supplementation, we observed that glucose (24.34%), triglycerides (35.78%), and HOMA-IR (40.10%) were reduced, and QUICKI (12.16%) increased compared to HFD rats. Furthermore, in skeletal muscle, we detected increased gene and protein expression of PPAR-α, PPAR-γ, insulin receptor (INSR), insulin receptor substrate 1 (ISR-1), phosphatidylinositol-3-kinase (PI3K), and glucose transporter 4 (GLUT-4). These findings suggest that ω-3 PUFAs decrease insulin resistance of obese skeletal muscle.

In Silico and In Vivo Evaluation of the Maqui Berry (Aristotelia chilensis (Mol.) Stuntz) on Biochemical Parameters and Oxidative Stress Markers in a Metabolic Syndrome Model.

Metabolic syndrome (MetS) is a complex disease that includes metabolic and physiological alterations in various organs such as the heart, pancreas, liver, and brain. Reports indicate that blackberry consumption, such as maqui berry, has a beneficial effect on chronic diseases such as cardiovascular disease, obesity, and diabetes. In the present study, in vivo and in silico studies have been performed to evaluate the molecular mechanisms implied to improve the metabolic parameters of MetS. Fourteen-day administration of maqui berry reduces weight gain, blood fasting glucose, total blood cholesterol, triacylglycerides, insulin resistance, and blood pressure impairment in the diet-induced MetS model in male and female rats. In addition, in the serum of male and female rats, the administration of maqui berry (MB) improved the concentration of MDA, the activity of SOD, and the formation of carbonyls in the group subjected to the diet-induced MetS model. In silico studies revealed that delphinidin and its glycosylated derivatives could be ligands of some metabolic targets such as α-glucosidase, PPAR-α, and PPAR-γ, which are related to MetS parameters. The experimental results obtained in the study suggest that even at low systemic concentrations, anthocyanin glycosides and aglycones could simultaneously act on different targets related to MetS. Therefore, these molecules could be used as coadjuvants in pharmacological interventions or as templates for designing new multitarget molecules to manage patients with MetS.

Effects of Five Coumarins and Standardized Extracts from Tagetes lucida Cav. on Motor Impairment and Neuroinflammation Induced with Cuprizone.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with no curative treatment, and the available therapies aim to modify the course of the disease. It has been demonstrated that extracts of Tagetes lucida have immunomodulatory and neuroprotective effects. This work induced motor damage and neuroinflammation in male BALB/c mice by oral administration of cuprizone (CPZ) (40 mg/kg) for five weeks. In addition, the extracts and coumarins of Tagetes lucida (25 mg/kg) were used to control these damage variables; during the experiment, animals were subject to behavioral tests, and at the end of 5 weeks, mice from each group were used to measure the integrity of biological barriers (brain, kidneys, and spleen) through the extravasation test with blue Evans dye. In another group of animals, the ELISA method measured the brain concentrations of IL-1ß, IL-4, IL-10, and TNF-α. The results presented here allow us to conclude that the extracts and coumarins IC, HN, PE, DF, and SC of Tagetes lucida exert a neuroprotective effect by controlling the motor damage and neuroinflammation by increasing the expression of IL-4 and IL-10 and decreasing IL-1ß and TNF-α; notably, these treatments also protect organs from vascular permeability increase, mainly the BBB, in mice with CPZ-induced experimental encephalomyelitis (VEH * p < 0.05). However, more studies must be carried out to elucidate the molecular mechanisms of the pharmacological effects of this Mexican medicinal plant.

LC-MS Fingerprinting Development for Standardized Precipitate from Agastache mexicana, Which Induces Antihypertensive Effect through NO Production and Calcium Channel Blockade.

The aim of this work was to evaluate the vasorelaxant and antihypertensive effects of a standardized precipitate of the hydroalcoholic extract from Agastache mexicana (PPAm), comprising ursolic acid, oleanolic acid, acacetin, luteolin and tilianin, among others. In the ex vivo experiments, preincubation with L-NAME (nonspecific inhibitor of nitric oxide synthases) reduced the relaxation induced by PPAm; nevertheless, preincubation with indomethacin (nonspecific inhibitor of cyclooxygenases) did not generate any change in the vasorelaxation, and an opposed effect was observed to the contraction generated by CaCl2 addition. Oral administration of 100 mg/kg of PPAm induced a significant acute decrease in diastolic (DBP) and systolic (SBP) blood pressure in spontaneously hypertensive rats, without changes in heart rate. Additionally, PPAm showed a sustained antihypertensive subacute effect on both DBP and SBP for 10 days compared to the control group. On the other hand, human umbilical vein cells treated with 10 µg/mL of PPAm showed a significant reduction (p < 0.05) in intracellular adhesion molecule-1, compared to the control, but not on vascular cell adhesion molecule-1. In conclusion, PPAm induces a significant antihypertensive effect in acute- and subacute-period treatments, due to its direct vasorelaxant action on rat aortic rings through NO production and Ca2+ channel blockade.

Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of Plantago australis.

Plantago australis Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. P. australis was collected in the state of Morelos, México. The hydroalcoholic extract (HAEPa) of P. australis was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAEPa significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAEPa induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD50 of HAEPa was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAEPa induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression.

Open-label phase I/II clinical trial of SARS-CoV-2 receptor binding domain-tetanus toxoid conjugate vaccine (FINLAY-FR-2) in combination with receptor binding domain-protein vaccine (FINLAY-FR-1A) in children.

OBJECTIVES: To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines. METHODS: A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results. RESULTS: Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval [CI] 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron. CONCLUSION: The heterologous scheme was safe and immunogenic in children 3-18 y/o. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000374.

La pediatría social. Herramienta necesaria para combatir la pandemia de COVID-19 en Cuba

Introducción: La pediatría social se orienta hacia la atención integral del niño. Estudia las causas sociales que alteran su salud y también los problemas de esta índole que repercuten en su entorno social. En el contexto de la actual pandemia, caracterizada por alta morbilidad y mortalidad, se produjeron significativas consecuencias psicosociales. Objetivo: Describir el impacto de la pediatría social sobre la salud infanto-juvenil durante la pandemia de COVID-19. Métodos: Se realizó una revisión en las bases de datos bibliográficas PubMed y BVS. Se empleó el Google Académico como motor de búsqueda. Se utilizaron, en español y en inglés, los siguientes descriptores: pediatría social, pandemia COVID-19, aislamiento social, bienestar psicológico, salud mental y población pediátrica. Análisis y síntesis de la información: Se expusieron argumentos desde la mirada psicosocial del pediatra, relacionados con el desarrollo y el bienestar socioemocional de los niños, y la repercusión sobre ellos del aislamiento social; además, se describió el impacto de la pandemia en la infancia, y el papel desempeñado por el especialista y otros profesionales vinculados con la atención pediátrica. Conclusiones: La pandemia se caracterizó por afectar todas las esferas de la vida del niño. La pediatría social resultó indispensable en el enfrentamiento de las consecuencias médico-biológicas, psicológicasy sociales que ocasionó el azote de la COVID-19, por lo que su rol influyó en el restablecimiento del equilibrio biopsicosocial de la población infantil.

Introduction: Social pediatrics is oriented towards the comprehensive care of children. It studies the social causes that alter their health, and also the problems of this nature that affect their social environment. In the context of the current pandemic, characterized by high morbidity and mortality, there were significant psychosocial consequences. Objective: To describe the impact of social pediatrics on children and adolescents health during the COVID-19 pandemic. Methods: A review was conducted in the bibliographic databases PubMed and VHL. Google Scholar was used as a search engine. The following descriptors were used in Spanish and English: social pediatrics, COVID-19 pandemic, social isolation, psychological well-being, mental health and pediatric population. Analysis and synthesis of information: Arguments were presented from the psychosocial perspective of the pediatrician, related to the development and socio-emotional well-being of children, and the impact on them of social isolation. In addition, the impact of the pandemic on children was described, and the role played by the specialists and other professionals linked to pediatric care. Conclusions: The pandemic was characterized by affecting all spheres of the child's life. Social pediatrics was indispensable in confronting the medical-biological, psychological and social consequences caused by the scourge of COVID-19, so its role influenced the restoration of the biopsychosocial balance of the children population.

Glycine Effect on the Expression Profile of Orphan Receptors GPR21, GPR26, GPR39, GPR82 and GPR6 in a Model of Inflammation in 3T3-L1 Cells.

BACKGROUND: Chronic or low-grade inflammation is a process where various immune cells are recruited from the periphery into adipose tissue. This event gives rise to localised inflammation, in addition to having a close interaction with cardiometabolic pathologies where the mediation of orphan receptors is observed. The aim of this study was to analyse the participation of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in a chronic inflammatory process in 3T3-L1 cells. The 3T3-L1 cells were stimulated with TNF-α (5 ng/mL) for 60 min as an inflammatory model. Gene expression was measured by RT-qPCR. RESULTS: We showed that the inflammatory stimulus of TNF-α in adipocytes decreased the expression of the orphan receptors GPR21, GPR26, GPR39, GPR82 and GPR6, which are related to low-grade inflammation. CONCLUSIONS: Our results suggest that GPR21 and GPR82 are modulated by glycine, it shows a possible protective role in the presence of an inflammatory environment in adipocytes, and they could be a therapeutic target to decrease the inflammation in some diseases related to low-grade inflammation such as diabetes, obesity and metabolic syndrome.

Herniarin, Dimethylfraxetin and Extracts from Tagetes lucida, in Psychosis Secondary to Ketamine and Its Interaction with Haloperidol.

Tagetes lucida Cav., is a medicinal plant used in Mexico to alleviate different disorders related to alterations of the central nervous system, such as behaviors associated with psychosis. The present work evaluated the effect of different extracts separated from this plant, TlHex, TlEA, TlMet, and TlAq, and of two isolated coumarins, herniarin (HN) and dimethylfraxetin (DF), on haloperidol-induced catalepsy (HAL), and psychotic behaviors provoked with a glutamatergic antagonist, ketamine (KET) on ICR mice. The extracts TlEA, TlAq, and the isolated compounds HN and DF, induced an increment of the cataleptic effect of HAL. Schizophrenia-like symptoms caused by KET were analyzed through the behavior of the animals in the open field (OFT), forced swimming (FST), passive avoidance test (PAT), and social interaction test (SIT). Treatments derived from T. lucida could interact with this substance in all tests except for FST, in which only TlMet blocks its activity. Mainly, TlEA, TlAq, HN, and DF, blocked the effects of KET on stereotyped behavior, hyperlocomotion, cognitive impairment, and detriment in the social interaction of rodents. T. lucida interacted with dopaminergic and glutamatergic systems.

Amputación digital en una paciente con úlcera del pie diabético / Digital amputation in a patient with diabetic foot ulcer

Este artículo consta solo de imágenes(AU)

Ribosomes: The New Role of Ribosomal Proteins as Natural Antimicrobials.

Moonlighting proteins are those capable of performing more than one biochemical or biophysical function within the same polypeptide chain. They have been a recent focus of research due to their potential applications in the health, pharmacological, and nutritional sciences. Among them, some ribosomal proteins involved in assembly and protein translation have also shown other functionalities, including inhibiting infectious bacteria, viruses, parasites, fungi, and tumor cells. Therefore, they may be considered antimicrobial peptides (AMPs). However, information regarding the mechanism of action of ribosomal proteins as AMPs is not yet fully understood. Researchers have suggested that the antimicrobial activity of ribosomal proteins may be associated with an increase in intracellular reactive oxidative species (ROS) in target cells, which, in turn, could affect membrane integrity and cause their inactivation and death. Moreover, the global overuse of antibiotics has resulted in an increase in pathogenic bacteria resistant to common antibiotics. Therefore, AMPs such as ribosomal proteins may have potential applications in the pharmaceutical and food industries in the place of antibiotics. This article provides an overview of the potential roles of ribosomes and AMP ribosomal proteins in conjunction with their potential applications.

Hepaticoyeyunostomía asistida por Robot vs la técnica abierta en un Hospital de tercer nivel / Robotic-Assisted vs open technique Hepaticojejunostomy in a third level Hospital

Resumen A pesar de la evidencia científica de la seguridad, la eficacia de la cirugía robótica, existen pocas publicaciones en la reparación de la vía biliar. El principal objetivo de este estudio fue evaluar los resultados de la hepaticoyeyunostomía en Y de Roux asistida por robot (HYR) y la hepaticoyeyunostomía en Y de Roux abierta (HYA) en el HCM en el periodo de enero de 2012 a enero de 2019. Este es un estudio retrospectivo se recolectaron los datos sociodemográficos, las principales comorbilidades y se determinó la principal indicación quirúrgica de la hepaticoyeyunostomía; se agruparon según la indicación quirúrgica para comparar el sangrado transoperatorio, tiempo quirúrgico, los días de estancia hospitalaria y morbilidad entre la HYR vs HYA. Se registraron 78 hepaticoyeyunostomías (31 fueron HYR y 47 HYA), la edad promedio fue 55.2 ± 17.7 años predominio del género femenino, la principal comorbilidad fue la hipertensión arterial. La principal indicación quirúrgica de hepaticoyeyunostomía fue la disrupción de vía la biliar, en estos pacientes se encontró menor tiempo quirúrgico, días de hospitalización, y morbilidad en los pacientes sometidos a HYR que los pacientes tratados mediante HYA.

Abstract Despite the scientific evidence of safety, the efficacy of robotic surgery, there are few publications on bile duct repair. The main objective of this study was to evaluate the results of Robotic-assisted Hepaticojejunostomy (RHJ) versus open Hepaticoyejunostomy (OHJ) in the HCM during the period from January 2012 to January 2019. This is a retrospective study, database of patients was collected: sociodemographic data, the main comorbidities, and the main surgical indication of hepaticojejunostomy were determined. They were grouped according to the surgical indication to compare: transoperative bleeding, surgical time, hospital length of stay and morbidity RHJ vs. OHJ. Seventy-eight hepaticojejunostomies were registered (31 RHJ and 47 OHJ), the average age was 55.2 ± 17.7 years, predominantly female, the main comorbidity was arterial hypertension. The main surgical indication of hepaticoyeynostomy was bile duct disruption. Shorter surgical time, days of hospitalization, and morbidity were found in patients undergoing RHJ than patients treated with OHJ.

Synthesis, in vitro, in silico and in vivo hypoglycemic and lipid-lowering effects of 4-benzyloxy-5-benzylidene-1,3-thiazolidine-2,4-diones mediated by dual PPAR α/γ modulation.

In current work, we prepared a series of nine 4-benzyloxy-5-benzylidene-1,3-thiazolidine-2,4-diones using a two-step pathway. Compounds 1-9 were tested in vitro using a set of three proteins recognized as important targets in diabetes and related diseases: PPARα, PPARγ, and GLUT-4. Compounds 1-3, 5, and 7 showed significant increases in the mRNA expression of PPARγ and GLUT-4, whereas compounds 1-3 did it over PPARα. Compounds 1-3 were identified as a dual PPAR α/γ modulators and were selected for evaluating the in vivo antidiabetic action at 100 mg/kg dose, being orally actives and decreasing blood glucose concentration in a hyperglycemic mice model, as well as reducing the triacylglycerides levels in normolipidemic rats. Docking and molecular dynamics studies were conducted to clarify the dual effect and binding mode of compounds 1-3 on both PPARs. Compounds 2 and 3 exhibited robust in vitro and in vivo efficacy and could be considered dual PPAR modulators with antidiabetic and antidyslipidemic effects.

Synthesis, In Vitro, In Vivo and In Silico Antidiabetic Bioassays of 4-Nitro(thio)phenoxyisobutyric Acids Acting as Unexpected PPARγ Modulators: An In Combo Study.

Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1-4, but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1-4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.

Steroidal saponin from Agave marmorata Roezl modulates inflammatory response by inhibiting NF-κB and AP-1.

Agave marmorata Roezl is an endemic succulent specie from the Oaxaca-Puebla area of Mexico. This plant is a medicinal recourse and contain a rich variety of saponins-type compounds with multiples biological effects. Some of them have been shown to be anticancer, antibacterial, or having anti-inflammatory and immunoregulation effects. This paper is the first scientific report to describe the pharmacological activity and chemistry of the saponin smilagenin-3-O-[ß-D-glucopyranosyl (1→2)-ß-D-galactopyranoside] (1), isolated from Agave marmorata Roezl. Saponin (1) displayed immunomodulating activity when assayed on cultured macrophages. It inhibits NO production (EC50 = 5.6 mg/ml, Emax = 101%), as well as NF-κB expression (EC50 = 0.086 mg/ml, Emax = 90%). Using bioinformatic molecular docking, we identified a new smilagenin- PI3K kinase interaction site.

Biomarcadores en la sepsis y su valor predictivo en pacientes pediátricos

RESUMEN Introducción: La sepsis en niños, es causa de gran preocupación entre los pediatras. La incorporación de nuevos biomarcadores posibilita la obtención de un diagnóstico rápido y preciso. Objetivo: Determinar la capacidad predictiva de mortalidad de un grupo de biomarcadores en pacientes pediátricos con sepsis. Métodos: Estudio multicéntrico descriptivo analítico, prospectivo y longitudinal en 60 pacientes ingresados en dos Unidades de cuidados intensivos: Hospital Dediátrico docente "Borrás-Marfán" y Hospital Pediátrico Universitario "William Soler" entre diciembre de 2016 y diciembre de 2018, con diagnóstico de sepsis severa y shock séptico. Se caracterizó la muestra según variables demográficas, origen y estadios de la sepsis y mortalidad; además se determinaron los biomarcadores más sensibles para el diagnóstico inicial y de mejor valor predictivo. Se empleó la estadística descriptiva y se realizaron pruebas diagnósticas con más de dos resultados (curva ROC). Resultados: Se observó una distribución similar de la muestra en cuanto sexo, con una media edad promedio de 5 años; dos tercios se diagnosticaron como sepsis graves y 23,3 % falleció El lactato fue el marcador con mayor sensibilidad. Conclusiones: Los biomarcadores más sensibles para el diagnóstico inicial de la sepsis fueron: lactato, proteína C reactiva y velocidad de sedimentación globular; los dos primeros junto a los leucocitos, neutrófilos y plaquetas, también resultaron buenos predictores de mortalidad. La velocidad de sedimentación globular fue el biomarcador predictor de mortalidad menos significativo.

ABSTRACT Introduction: Sepsis in children is a cause of great concern among pediatricians. New biomarkers makes it possible to obtain quick and accurate diagnosis. Objective: To determine the predictive capacity of mortality of a group of biomarkers in pediatric patients with sepsis. Methods: An analytical, prospective and longitudinal descriptive multicenter study was carried out in 60 patients admitted to two intensive care units at Borrás-Marfán Teaching Pediatric Hospital and William Soler University Pediatric Hospital from December 2016 to December 2018. These patients had a diagnosis of sepsis severe and septic shock. The sample was characterized according to demographic variables, origin and stages of sepsis and mortality. In addition, the most sensitive biomarkers for the initial diagnosis and the best predictive value were determined. Descriptive statistics were used and diagnostic tests were performed with more than two results (ROC curve). Results: A similar distribution of the sample was observed in terms of sex, with average age of 5 years; two thirds were diagnosed as severe sepsis and 23.3% died. Lactate was the marker with the highest sensitivity. Conclusions: The most sensitive biomarkers for the initial diagnosis of sepsis were lactate, C-reactive protein and erythrocyte sedimentation rate; the first two, together with leukocytes, neutrophils, and platelets, were also good predictors of mortality. Erythrocyte sedimentation rate was the least significant predictor of mortality biomarker.

High fructose exposure modifies the amount of adipocyte-secreted microRNAs into extracellular vesicles in supernatants and plasma.

BACKGROUND: High fructose exposure induces metabolic and endocrine responses in adipose tissue. Recent evidence suggests that microRNAs in extracellular vesicles are endocrine signals secreted by adipocytes. Fructose exposure on the secretion of microRNA by tissues and cells is poorly studied. Thus, the aim of this study was to evaluate the effect of fructose exposure on the secretion of selected microRNAs in extracellular vesicles from 3T3-L1 cells and plasma from Wistar rats. METHODS: 3T3-L1 cells were exposed to 550 µM of fructose or standard media for four days, microRNAs levels were determined in extracellular vesicles of supernatants and cells by RT-qPCR. Wistar rats were exposed to either 20% fructose drink or tap water for eight weeks, microRNAs levels were determined in extracellular vesicles of plasma and adipose tissue by RT-qPCR. RESULTS: This study showed that fructose exposure increased the total number of extracellular vesicles released by 3T3-L1 cells (p = 0.0001). The levels of miR-143-5p were increased in extracellular vesicles of 3T3-L1 cells exposed to fructose (p = 0.0286), whereas miR-223-3p levels were reduced (p = 0.0286). Moreover, in plasma-derived extracellular vesicles, miR-143-5p was higher in fructose-fed rats (p = 0.001), whereas miR-223-3p (p = 0.022), miR-342-3p (p = 0.0011), miR-140-5p (p = 0.0129) and miR-146b-5p (p = 0.0245) were lower. CONCLUSION: Fructose exposure modifies the levels of microRNAs in extracellular vesicles in vitro and in vivo. In particular, fructose exposure increases miR-143-5p, while decreases miR-223-3p and miR-342-3p.

α-Amyrin induces GLUT4 translocation mediated by AMPK and PPARδ/γ in C2C12 myoblasts.

α-Amyrin, a natural pentacyclic triterpene, has an antihyperglycemic effect in mice and dual PPARδ/γ action in 3T3-L1 adipocytes, and potential in the control of type 2 diabetes (T2D). About 80% of glucose uptake occurs in skeletal muscle cells, playing a significant role in insulin resistance (IR) and T2D. Peroxisome-proliferator activated receptors (PPARs), in particular PPARδ and PPARγ, are involved in the regulation of lipids and carbohydrates and, along with adenosine-monophosphate (AMP) - activated protein kinase (AMPK) and protein kinase B (Akt), are implicated in translocation of glucose transporter 4 (GLUT4); however, it is still unknown whether α-amyrin can affect these pathways in skeletal muscle cells. Our objective was to determine the action of α-amyrin in PPARδ, PPARγ, AMPK, and Akt in C2C12 myoblasts. The expression of PPARδ, PPARγ, fatty acid transporter protein (FATP), and GLUT4 was quantified using reverse transcription quantitative PCR and Western blot. α-Amyrin increased these markers along with phospho-AMPK (p-AMPK) but not p-Akt. Molecular docking showed that α-amyrin acts as an AMPK-allosteric activator, and may be related to GLUT4 translocation, as evidenced by confocal microscopy. These data support that α-amyrin could have an insulin-mimetic action in C2C12 myoblasts and should be considered as a bioactive molecule for new multitarget drugs with utility in T2D and other metabolic diseases.

Starch Edible Films/Coatings Added with Carvacrol and Thymol: In Vitro and In Vivo Evaluation against Colletotrichum gloeosporioides.

The aim of this work was to evaluate the in vitro and in vivo effectiveness of thymol and carvacrol added to edible starch films and coatings against Colletotrichum gloeosporioides. In vitro evaluation consisted of determining minimal inhibitory concentration (MIC) of carvacrol and thymol was determined at different pH values against Colletotrichum gloeosporioides. With MIC values, binary mixtures were developed. From these results, two coatings formulations were in vivo evaluated on mango and papaya. Physicochemical analysis, color change, fruit lesions and C. gloeosporioides growth were determined during storage. In vitro assay indicated that the MIC value of carvacrol and thymol against C. gloeosporioides was 1500 mg/L at pH 5. An additive effect was determined with 750/750 and 1125/375 mg/L mixtures of carvacrol and thymol, respectively. Coated fruits with selected mixtures of carvacrol and thymol presented a delay in firmness, maturity index and color change. Moreover, a fungistatic effect was observed due to a reduction of lesions in coated fruits. These results were corroborated by the increase in the lag phase value and the reduction of the growth rate. Carvacrol and thymol incorporated into edible films and coatings are able to reduce the incidence of anthracnose symptoms on mango and papaya.

Diabetic Retinopathy: Important Biochemical Alterations and the Main Treatment Strategies.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired glucose homeostasis, insulin resistance and hyperglycemia. Among its serious multisystemic complications is diabetic retinopathy (DR), which develops slowly and often insidiously. This disorder-the most common cause of vision loss in working-age adults-is characterized by functional and morphological changes in the retina. It results from the exacerbation of ischemic and inflammatory conditions prompted by alterations in the blood vessels, such as the development of leukostasis, thickening of the basement membrane, retinal neovascularization and fibrovascular tissue formation at the vitreoretinal interface. The pathogenic alterations are usually triggered at the biochemical level, involving a greater activity in 4 pathways: the polyol pathway, the hexosamine pathway, the formation of advanced glycation end-products and the activation of protein kinase C isoforms. When acting together, these pathways give rise to increased levels of reactive oxygen species and decreased levels of endogenous antioxidant agents, thus generating oxidative stress. All current therapies are aimed at the later stages of DR, and their application implies side effects. One possible strategy for preventing the complications of DM is to counteract the elevated superoxide production stemming from a high level of blood glucose. Accordingly, some treatments are under study for their capacity to reduce vascular leakage and avoid retinal ischemia, retinal neovascularization and macular edema. The present review summarizes the biochemical aspects of DR and the main approaches for treating it.