Paediatrics congenital heart disease is associated with plasma miRNAs.

BACKGROUND: Congenital heart disease (CHD) are the most common malformations from birth. The severity of the different forms of CHD varies extensively from superficial mild lesions with follow-up for decades without any treatment to complex cyanotic malformations requiring urgent surgical intervention. microRNAs have been found to be crucial in cardiac development, giving rise to possible phenotypes in CHD. OBJECTIVES: We aimed to evaluate the expression of miRNAs in 86 children with CHD and divided into cyanotic and non-cyanotic heart defects and 110 controls. METHODS: The miRNAs expression of miR-21-5p, miR-155-5p, miR-221-3p, miR-26a-5p, and miR-144-3p were analyzed by RT-qPCR. In addition, the expressions of the miRNAs studied were correlated with the clinical characteristics of both the children and the mothers. RESULTS: The expression levels of miR-21-5-5p, miR-15-5p5, miR-221-3p, and miR-26-5p significantly differed between CHD and control subjects. Moreover, miR-21-5p levels were higher in patients with cyanotic versus non-cyanotic CHD patients. CONCLUSION: The expression levels of miRNAs of pediatric patients with CHD could participating in the development of cardiac malformations. Additionally, the high expression of miR-21-5p in cyanotic CHD children may be related to greater severity of illness relative to non-cyanotic CHD. IMPACT: This study adds to knowledge of the association between microRNAs and congenital heart disease in children. The expression levels of miR-21-5-5p, miR-15-5p5, miR-221-3p, and miR-26-5p of pediatric patients with CHD could be involved in the development and phenotype present in pediatric patients. miR-21-5p may help to discriminate between cyanotic and non-cyanotic CHD. In the future, the miRNAs studied could have applications as clinical biomarkers.

Evaluation of the participation of ABCA1 transporter in epicardial and mediastinal adipose tissue from patients with coronary artery disease

ABSTRACT Objective: Recent studies have shown a relationship between adipose tissue and coronary artery disease (CAD). The ABCA1 transporter regulates cellular cholesterol content and reverses cholesterol transport. The aim of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) R230C, C-17G, and C-69T and their expression in epicardial and mediastinal adipose tissue in Mexican patients with CAD. Subjects and methods: The study included 71 patients with CAD and a control group consisting of 64 patients who underwent heart valve replacement. SNPs were determined using TaqMan probes. mRNA was extracted using TriPure Isolation from epicardial and mediastinal adipose tissue. Quantification and expression analyses were done using RT-qPCR. Results: R230C showed a higher frequency of the GG genotype in the CAD group (70.4%) than the control group (57.8%) [OR 0.34, 95% CI (0.14-0.82) p = 0.014]. Similarly, C-17G (rs2740483) showed a statistically significant difference in the CC genotype in the CAD group (63.3%) in comparison to the controls (28.1%) [OR 4.42, 95% CI (2.13-9.16), p = 0.001]. mRNA expression in SNP R230C showed statistically significant overexpression in the AA genotype compared to the GG genotype in CAD patients [11.01 (4.31-15.24) vs. 3.86 (2.47-12.50), p = 0.015]. Conclusion: The results suggest that the GG genotype of R230C and CC genotype of C-17G are strongly associated with the development of CAD in Mexican patients. In addition, under-expression of mRNA in the GG genotype in R230C is associated with patients undergoing revascularization.

Hepatoprotective Mechanisms Induced by Spinach Methanolic Extract in Rats with Hyperglycemia-An Immunohistochemical Analysis.

Spinach methanolic extract (SME) has a hepatoprotective effect due to its polyphenolic antioxidants; however, its action in parenchymal (PQ) and non-parenchymal (nPQ) cells remains unknown. This study investigates the hepatoprotective effect of SME on streptozotocin-induced hyperglycemic rats (STZ), focusing on immunohistochemical analyses. Methods: The extract was prepared, and the total polyphenols and antioxidant activity were quantified. Adult male Wistar rats were divided into four groups (n = 8): normoglycemic rats (NG), STZ-induced hyperglycemic (STZ), STZ treated with 400 mg/kg SME (STZ-SME), and NG treated with SME (SME) for 12 weeks. Serum liver transaminases and lipid peroxidation levels in tissue were determined. The distribution pattern and relative levels of markers related to oxidative stress [reactive oxygen species (ROS), superoxide dismutase-1, catalase, and glutathione peroxidase-1], of cytoprotective molecules [nuclear NRF2 and heme oxygenase-1 (HO-1)], of inflammatory mediators [nuclear NF-κB, TNF-α], proliferation (PCNA), and of fibrogenesis markers [TGF-ß, Smad2/3, MMP-9, and TIMP1] were evaluated. Results: SME had antioxidant capacity, and it lowered serum transaminase levels in STZ-SME compared to STZ. It reduced NOX4 staining, and lipid peroxidation levels were related to low formation of ROS. In STZ-SME, the immunostaining for antioxidant enzymes increased in nPQ cells compared to STZ. However, enzymes were also localized in extra and intracellular vesicles in STZ. Nuclear NRF2 staining and HO-1 expression in PQ and nPQ were higher in STZ-SME than in STZ. Inflammatory factors were decreased in STZ-SME and were related to the percentage decrease in NF-κB nuclear staining in nPQ cells. Similarly, TGF-ß (in the sinusoids) and MMP-9 (in nPQ) were increased in the STZ-SME group compared to the other groups; however, staining for CTGF, TIMP1, and Smad2/3 was lower. Conclusions: SME treatment in hyperglycemic rats induced by STZ may have hepatoprotective properties due to its scavenger capacity and the regulation of differential expression of antioxidant enzymes between the PQ and nPQ cells, reducing inflammatory and fibrogenic biomarkers in liver tissue.

Evaluation of the participation of ABCA1 transporter in epicardial and mediastinal adipose tissue from patients with coronary artery disease.

Objective: Recent studies have shown a relationship between adipose tissue and coronary artery disease (CAD). The ABCA1 transporter regulates cellular cholesterol content and reverses cholesterol transport. The aim of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) R230C, C-17G, and C-69T and their expression in epicardial and mediastinal adipose tissue in Mexican patients with CAD. Subjects and methods: The study included 71 patients with CAD and a control group consisting of 64 patients who underwent heart valve replacement. SNPs were determined using TaqMan probes. mRNA was extracted using TriPure Isolation from epicardial and mediastinal adipose tissue. Quantification and expression analyses were done using RT-qPCR. Results: R230C showed a higher frequency of the GG genotype in the CAD group (70.4%) than the control group (57.8%) [OR 0.34, 95% CI (0.14-0.82) p = 0.014]. Similarly, C-17G (rs2740483) showed a statistically significant difference in the CC genotype in the CAD group (63.3%) in comparison to the controls (28.1%) [OR 4.42, 95% CI (2.13-9.16), p = 0.001]. mRNA expression in SNP R230C showed statistically significant overexpression in the AA genotype compared to the GG genotype in CAD patients [11.01 (4.31-15.24) vs. 3.86 (2.47-12.50), p = 0.015]. Conclusion: The results suggest that the GG genotype of R230C and CC genotype of C-17G are strongly associated with the development of CAD in Mexican patients. In addition, under-expression of mRNA in the GG genotype in R230C is associated with patients undergoing revascularization.

The effects of fresh mango consumption on gut health and microbiome - Randomized controlled trial.

Some individual fruits have been widely researched for their effects on overall health and correlations with chronic diseases. The beneficial effects of mango supplementation on metabolic diseases have been detected. However, research into mango consumption on gut health, including the microbiome, is limited to processed mango preparations or peels. Our goal was to examine the effects of fresh mango consumption on the gut microbiome, gut permeability proteins, and bowel movement habits in overweight/obese individuals. In a 12-week crossover design study, 27 participants consumed 100 kcal/day of either mangos or low-fat cookies with a washout period of 4 weeks. The mango intervention showed higher Shannon-Wiener and Simpson alpha diversity indices of the microbiome than the low-fat cookie intervention in week 4. Significant differences in beta diversity of the microbiome were found between diet interventions at week 12. Mango consumption increased the abundance of Prevotella maculosa, Corynebacterium pyruviciproducens, and Mogibacterium timidum while it decreased Prevotella copri. Low-fat cookie intake increased Cyanobacterium aponinum and Desulfovibrio butyratiphilus and reduced Alloscardovia omnicolens. There were no significant differences in circulating gut permeability protein (ZO-1, claudin-2, and occludin) levels. There was a slight increase in the amount of bowel movement with mango consumption, but no significant findings for frequency, consistency, strain, pain, and constipation in bowel movement between trials. Given these results, it can be concluded that consumption of mango may have positive effects on the gut health, which may yield possible health benefits for chronic disease that deserve further study.

Effects of Mixed Nut Consumption on Blood Glucose, Insulin, Satiety, and the Microbiome in a Healthy Population: A Pilot Study.

Nuts contain many health-promoting nutrients, fiber, and phytochemicals. Nut consumption has been reported to improve several chronic disease risk factors. Most studies to date have investigated single variety nut consumption. A nut mixture may offer a more diverse array of nutrients over single variety nuts. The primary outcome of this study was to examine the effects of mixed nut consumption on postprandial glucose, insulin, and satiety in healthy young adults. Exploratory outcomes include the effects of daily nut consumption on stool microbiome and bowel movement patterns. Twenty participants were randomized to consume either 42 g of mixed nuts or 46 g of potato chips daily for 3 weeks. Mixed nut consumption did not alter postprandial blood glucose and insulin, while potato chip consumption increased glucose and insulin (P < .05). There were no significant differences in fasting blood glucose or insulin for either snack after 3 weeks of daily consumption. Both snacks increased satiety while there were no significant differences in body weight, body fat, blood pressure, waist-to-hip ratio, or anxiety. After 3 weeks of snack consumption, both groups significantly reduced straining during bowel movements while the mixed nut group slightly increased stool amount. There were no significant changes in microbiome composition for either group; however, there was a nonsignificant trend toward increased Firmicutes to Bacteroidetes ratio in the potato chip group and an opposite trend in the mixed nut group. The results of this study suggest that mixed nuts are a healthy alternative for blood sugar control. The study was registered at ClinicalTrials.gov, Number: NCT03375866.

Blenderized watermelon consumption decreases body mass index, body mass index percentile, body fat and HbA1c in children with overweight or obesity.

OBJECTIVES: Childhood obesity increases risk factors related to metabolic diseases. Watermelon's bioactive components can help reduce these risk factors. However, no study has investigated the effects of whole watermelon including both the flesh and rind or have assessed the impacts of any form of watermelon on children with overweight or obesity. The goal of this study was to examine the effects of whole-blenderized watermelon (BWM) consumption on cardiometabolic risk factors. METHODS: A randomized, cross-over clinical design was implemented. Boys and girls ages 10-17 years with overweight or obesity (BMI ≥ 85th percentile) consumed one cup of BWM or an isocaloric sugar-sweetened beverage (control) every day for 8 weeks with a 4-week washout between trials. Anthropometrics, dietary, biochemical and clinical measures were obtained before and at the end of each trial. RESULTS: A total of 17 participants completed the study. Eight weeks of BWM intake significantly decreased BMI (p = 0.032), BMI percentile (BMIP) (p = 0.038), body fat percentage (p = 0.036), and haemoglobin A1c (HbA1c) (p = 0.012) compared to the sugar-sweetened beverage. Sugar-sweetened beverage consumption increased BMIP (p = 0.014) compared to baseline. No significant differences were observed for inflammation, blood glucose, insulin, lipids, liver function enzymes, and satiety hormones. CONCLUSIONS: The results support that BWM consumption improved some cardiometabolic risk factors including BMI, BMIP, body fat, and HbA1c. Watermelon is a potential alternative to unhealthful snacks for improving anthropometry and some risk factors related to obesity in children.

La importancia de la determinación de la deuda de oxígeno en el perioperatorio / The importance of oxygen debt determination in the perioperative period

Resumen: El fenómeno de la deuda de oxígeno (dO2) descrito hace varias décadas en el contexto del ejercicio físico se ha incorporado progresivamente al terreno de la medicina. En particular se ha utilizado durante los cambios hemodinámicos producidos por la cirugía y la anestesia en los pacientes de alto riesgo. La dO2 se definió como el aumento en la cantidad de oxígeno consumida por el organismo inmediatamente después de realizar un ejercicio físico hasta que el consumo se normaliza nuevamente. En el perioperatorio se llega a producir cuando se presenta un desbalance entre la oferta (DO2) y la demanda de oxígeno (VO2) que lleva a hipoxia tisular. El grado de la dO2 tisular se ha relacionado directamente con la falla de órganos múltiples y morbimortalidad perioperatoria. A pesar de los avances en la medicina, aún no es posible prevenir o disminuir la dO2 con la administración de líquidos o con el uso de agentes vasoactivos. Por lo que un retardo o manejo inadecuado de la hemodinámica perioperatoria producirá hipoperfusión e hipoxia tisular afectando los resultados de la cirugía. El conocimiento y la valoración de la dO2 es esencial durante la anestesia del paciente de alto riesgo. Para lograr este objetivo se requiere del uso de índices adecuados que permitan detectar y cuantificar la hipoperfusión tisular y el desbalance entre la DO2 y la VO2. En esta revisión se presentan los conceptos fundamentales de la dO2, su mecanismo, detección y cuantificación; además de las intervenciones para evitarla o disminuirla y las recomendaciones para los anestesiólogos con el fin de asegurar mejores resultados en los pacientes quirúrgicos de alto riesgo.

Abstract: The phenomenon of oxygen debt (dO2) described several decades ago in the context of physical exercise has been incorporated into medicine, particularly during the hemodynamic changes produced by surgery and anesthesia in high-risk patients. dO2 is defined as the increase in the amount of oxygen consumed by the body immediately after physical exercise until O2 consumption returns to normal. In the perioperative period, an imbalance between oxygen supply (DO2) and demand (VO2) could generate dO2. The degree of tissue dO2 has been directly related to multiple organ failure and perioperative morbimortality. Despite advances in medicine, it is not yet possible to prevent or lower the dO2 with fluid administration or vasoactive agents. Delay or inadequate management of hemodynamics could produce tissue hypoperfusion and hypoxia, affecting surgery outcomes. Knowledge and assessing dO2 during perioperative are essential during anesthesia for high-risk patients. Adequate indices are required to detect and quantify tissue hypoperfusion and the imbalance between DO2 and VO2 during anesthesia. This review presents the mechanism, detection, and quantification of dO2. In addition to interventions to avoid or reduce dO2 and recommendations for anesthesiologists to ensure better results in high-risk surgical patients.

Contribution of hyperglycemia-induced changes in microglia to Alzheimer's disease pathology.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive and functional impairments. The investigation of AD has focused on the formation of senile plaques, composed mainly by amyloid ß (Aß) peptide, and neurofibrillary tangles (NFTs) in the brain. Senile plaques and NFTs cause the excessive recruitment and activation of microglia, thus generating neuroinflammation and neuronal damage. Among the risk factors for the development of AD, diabetes has increasingly attracted attention. Hyperglycemia, the fundamental characteristic of diabetes, is involved in several mechanisms that give rise to microglial overactivation, resulting in neuronal damage and cognitive impairment. Indeed, various studies have identified the correlation between diabetes and AD. The aim of this review is to describe various mechanisms of the hyperglycemia-induced overactivation of microglia, which leads to neuroinflammation and neuronal damage and consequently contributes to the pathology of AD. The disruption of the regulation of microglial activity by hyperglycemia occurs through many mechanisms, including a greater production of reactive oxygen species (ROS) and glycation end products (AGEs), and a decrease in the elimination of Aß. The future direction of research on the relation between hyperglycemia and AD is addressed, such as the importance of determining whether the hyperglycemia-induced harmful effects on microglial activity can be reversed or attenuated if blood glucose returns to a normal level.

Fresh Mango Consumption Promotes Greater Satiety and Improves Postprandial Glucose and Insulin Responses in Healthy Overweight and Obese Adults.

Mangos are an understudied fruit rich in fiber and polyphenols that have been linked to better metabolic outcomes and promotion of satiety. The purpose of this study was to examine the effect of mango consumption on postprandial glucose, insulin, and satiety responses. Using a randomized crossover study design, 23 overweight and obese men and women consumed 100 kcal snacks of fresh mangos or isocaloric low-fat cookies on two separate occasions. Insulin and satiety hormones were measured at baseline and 45 min post-snack consumption. Glucose was measured at baseline, 30, 60, 90, and 120 min after snack consumption. Satiety questionnaires were completed at baseline and every 20 min for 120 min post-consumption. Both mangos and low-fat cookies increased insulin, with a significantly lower increase for mangos compared with low-fat cookies at 45 min post-snack consumption (P ≤ .05). Glucose increased at 30 min for both snacks; however, the increase was significantly higher for low-fat cookie consumption (P ≤ .05). Cholecystokinin increased after mangos and low-fat cookie consumption (P ≤ .05); however, no differences were detected between the snacks. Adiponectin increased after mango consumption (P ≤ .05) but not after low-fat cookies. Mango consumption reduced hunger, anticipated food consumption and thirst, and increased feelings of fullness (P ≤ .05). Low-fat cookie consumption increased fullness for a shorter time period and did not reduce participants' desire to eat. These results suggest that relative to a refined cookie snack, mangos promote greater satiety and improve postprandial glycemic responses. Future research on long-term effects of mango consumption on food intake, weight control, and glucose homeostasis is warranted. Clinical Trial Registration number: #NCT03957928.

Effects of fresh mango consumption on cardiometabolic risk factors in overweight and obese adults.

BACKGROUND & AIMS: In vitro and animal studies show antidiabetic, anti-inflammatory, and cardioprotective properties of mangos. The objective of this study was to examine the effects of fresh mango consumption compared to an isocaloric control snack on body weight, glucose, insulin, lipid profiles, liver function enzymes, inflammation, and antioxidant activity in overweight and obese adults (BMI ≥26 kg/m2). METHODS AND RESULTS: In a crossover design, 27 participants consumed 100 kcal/d of fresh mangos or isocaloric low-fat cookies daily for 12 weeks each, separated by a four-week washout period. Blood glucose, C-reactive protein (CRP), and aspartate transaminase activity significantly decreased while total antioxidant capacity significantly increased following mango consumption. There were no significant changes in body weight, body fat %, blood pressure, insulin, or lipid profile following mango consumption. Cookie consumption significantly increased body weight, insulin, CRP, and triglycerides. CONCLUSION: These results suggest that relative to the control snack, mangos may improve certain risk factors associated with overweight and obesity including improved glycemic control and reduced inflammation. CLINICAL TRIALS REGISTER: NCT03957928.

Current Proteomic and Metabolomic Knowledge of Zygotic and Somatic Embryogenesis in Plants.

Embryogenesis is the primary developmental program in plants. The mechanisms that underlie the regulation of embryogenesis are an essential research subject given its potential contribution to mass in vitro propagation of profitable plant species. Somatic embryogenesis (SE) refers to the use of in vitro techniques to mimic the sexual reproduction program known as zygotic embryogenesis (ZE). In this review, we synthesize the current state of research on proteomic and metabolomic studies of SE and ZE in angiosperms (monocots and dicots) and gymnosperms. The most striking finding was the small number of studies addressing ZE. Meanwhile, the research effort focused on SE has been substantial but disjointed. Together, these research gaps may explain why the embryogenic induction stage and the maturation of the somatic embryo continue to be bottlenecks for efficient and large-scale regeneration of plants. Comprehensive and integrative studies of both SE and ZE are needed to provide the molecular foundation of plant embryogenesis, information which is needed to rationally guide experimental strategies to solve SE drawbacks in each species.

May Measurement Month 2019: an analysis of blood pressure screening results from Mexico.

May Measurement Month 2019 (MMM19) in Mexico was an opportunistic survey, aimed to improve blood pressure (BP) awareness at the individual and population levels. This survey followed the methodology of MMM19, previously published. The total number of participants screened was 39 700, 56.7% female, 36.6% were of mixed ethnicity, mean age [standard deviation (SD)] was 46.9 (17.4) years, and mean body mass index was 27.2 (SD: 4.4) kg/m2. Seven per cent of the participants reported having diabetes, 2.4% reported having a myocardial infarction in the past, 1.1% stroke, 2.0% were pregnant at the time of the survey, 3.7% of women had suffered from hypertension in a previous pregnancy, 11.4% declared that they were smokers, and 47.0% drank alcohol at least once a week. After multiple imputations, of all 39 700 participants, 10 140 (25.5%) had hypertension; of all participants with hypertension, 43.8% were aware of their diagnosis, 41.7% were on antihypertensive medication, and 27.8% had controlled BP (systolic BP <140 mmHg and diastolic BP <90 mmHg). Of those on antihypertensive medication, 27.8% had controlled BP. In Mexico, MMM is the largest hypertension survey ever done, it provides complementary data to the existing information on arterial hypertension in the country and helps to increase the visibility of hypertension: a priority health problem.

Spinach Methanolic Extract Attenuates the Retinal Degeneration in Diabetic Rats.

It has been suggested that spinach methanolic extract (SME) inhibits the formation of advanced glycation end products (AGEs), which are increased during diabetes progression, so it is important to know if SME has beneficial effects in the diabetic retina. In this study, in vitro assays showed that SME inhibits glycation, carbonyl groups formation, and reduced-thiol groups depletion in bovine serum albumin incubated either reducing sugars or methylglyoxal. The SME effect in retinas of streptozotocin-induced diabetic rats (STZ) was also studied (n = 10) in the normoglycemic group, STZ, STZ rats treated with SME, and STZ rats treated with aminoguanidine (anti-AGEs reference group) during 12 weeks. The retina was sectioned and immunostained for Nε-carboxymethyl lysine (CML), receptor RAGE, NADPH-Nox4, inducible nitric oxide synthase (iNOS), 3-nitrotyrosine (NT), nuclear NF-κB, vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), S100B protein, and TUNEL assay. Lipid peroxidation was determined in the whole retina by malondialdehyde (MDA) levels. The results showed that in the diabetic retina, SME reduced the CML-RAGE co-localization, oxidative stress (NOX4, iNOS, NT, MDA), inflammation (NF-κB, VEGF, S100B, GFAP), and apoptosis (p < 0.05). Therefore, SME could attenuate the retinal degeneration by inhibition of CML-RAGE interaction.

La lesión miocárdica en el perioperatorio de cirugía no cardíaca / Myocardial injury in the perioperative period of non-cardiac surgery

Resumen: Estudios recientes sobre las causas de muerte en el postoperatorio de cirugía no cardíaca han identificado a la lesión miocárdica como una complicación que se asocia con eventos cardíacos adversos mayores que aumentan la mortalidad a 30 días. La lesión miocárdica se manifiesta como una elevación de las troponinas cardíacas que se produce durante o a los 30 días después de la cirugía, sin que los pacientes presenten síntomas y sin cambios en el electrocardiograma de superficie. En la actualidad, se busca mejorar el diagnóstico oportuno de esta complicación y desarrollar terapias preventivas. En esta revisión abordamos la evidencia de esta lesión, sus mecanismos fisiopatológicos y su manejo.

Abstract: Recent studies on the death causes in the postoperative period of non-cardiac surgery have identified myocardial injury as a complication that is associated with major adverse cardiac events that increase mortality at 30 days after surgery. This kind of myocardial lesion is characterized by the elevation of the cardiac troponins levels during or in the 30 days after the surgery, without symptoms ischemia or changes in the electrocardiogram. Currently, one main goal has been the timely diagnosis of this complication, besides preventive therapies development. The present review article examines the current body of knowledge of this injury, the physiopathological mechanisms and its management.

Tissue-specific proteome characterization of avocado seed during postharvest shelf life.

Avocado is a nutritious and economically important fruit, generating significant income for exporter countries. Recently, by-products of this fruit such as seeds and peels, have raised interest in different industries. However, the biochemical features of the nutraceutical value of these tissues have not been analyzed using molecular approaches during the postharvest shelf life (PSL). We carried out comparative proteomics using tandem mass tagging (TMT) and synchronous-precursor selection (SPS)-MS3. We analyzed testa, cotyledon, and embryo axes from avocado seeds at detachment from the tree (unripe), and after five (breaker) and ten days (ripe) of PSL. We identified 1968 proteins, from which 933 were specific to the testa, 167 to the embryo axis, and 23 to the cotyledon. The testa had a more dynamic proteome than the other tissues, resembling similar stress responses to those observed in peel tissues, such as down-accumulation of translational machinery, cell wall catabolism and synthesis of secondary metabolites. In contrast, the up-accumulation of the biosynthesis of l-glutamine, L-isoleucine, and l-serine was observed in all tissues. Our study provides the basic biochemical and physiological features of avocado seed during PSL and demonstrates that avocado seed tissues could potentially be used as a costless source of high-value compounds. SIGNIFICANCE: Avocado seed as a fruit by-product is a source of different valuable molecules, including those with nutraceutical properties. During PSL, several biochemical and physiological modifications occur in this dispersal unit, which also includes the alteration of several key metabolites' content. However, the proteome profile associated with different metabolic pathways that regulate the inner content of seed metabolites has not been previously studied. Our tissue-specific proteomics TMT-SPS-MS3-based provides the first evidence of molecular and physiological changes in avocado tissues during PSL delivering fundamental knowledge of this organ. In this vein, the modulation of secondary metabolites, amino acid, and sugar metabolism of avocado tissues during PLS can encourage these by-products exploitation in multiple industries.

Projecting the long-term benefits of single pill combination therapy for patients with hypertension in five countries.

OBJECTIVE: To project the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with multi-pill regimens for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico). METHODS: A microsimulation model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and combination therapy in the form of a single pill (SPC). Model inputs were derived from the Global Burden of Disease 2017 dataset. Simulated outcomes of mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD), and disability-adjusted life years (DALYs) were estimated for 1,000,000 patients on each treatment pathway. RESULTS: SPC therapy was projected to improve clinical outcomes over SLGS, FCC and CTP in all countries. SPC reduced mortality by 5.4% in Italy, 4.9% in Russia, 4.5% in China, 2.3% in South Korea and 3.6% in Mexico versus CTP and showed greater reductions in mortality than SLGS and FCC. The projected incidence of clinical events was reduced by 11.5% in Italy, 9.2% in Russia, 8.4% in China, 4.9% in South Korea and 6.7% in Mexico for SPC versus CTP. CONCLUSIONS: Ten-year projections indicated that combination therapies (FCC and SPC) are likely to reduce the burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence.

Phenylpropanoids Are Connected to Cell Wall Fortification and Stress Tolerance in Avocado Somatic Embryogenesis.

Somatic embryogenesis (SE) is a valuable model for understanding the mechanism of plant embryogenesis and a tool for the mass production of plants. However, establishing SE in avocado has been complicated due to the very low efficiency of embryo induction and plant regeneration. To understand the molecular foundation of the SE induction and development in avocado, we compared embryogenic (EC) and non-embryogenic (NEC) cultures of two avocado varieties using proteomic and metabolomic approaches. Although Criollo and Hass EC exhibited similarities in the proteome and metabolome profile, in general, we observed a more active phenylpropanoid pathway in EC than NEC. This pathway is associated with the tolerance of stress responses, probably through the reinforcement of the cell wall and flavonoid production. We could corroborate that particular polyphenolics compounds, including p-coumaric acid and t-ferulic acid, stimulated the production of somatic embryos in avocado. Exogen phenolic compounds were associated with the modification of the content of endogenous polyphenolic and the induction of the production of the putative auxin-a, adenosine, cellulose and 1,26-hexacosanediol-diferulate. We suggest that in EC of avocado, there is an enhanced phenylpropanoid metabolism for the production of the building blocks of lignin and flavonoid compounds having a role in cell wall reinforcement for tolerating stress response. Data are available at ProteomeXchange with the identifier PXD019705.

Non-inferiority comparative clinical trial between early oral REFEEDING and usual oral REFEEDING in predicted mild acute biliary pancreatitis.

BACKGROUND: The aim of the study was to compare the onset of oral feeding in the first 24 h after hospital admission with usual oral refeeding and determine whether the timing of the onset of oral feeding influences the recurrence of pain or alters the blood levels of pancreatic enzymes in patients with predicted mild acute biliary pancreatitis. METHODS: This non-inferiority randomized controlled trial was carried out between September 2018 and June 2019 after receiving authorization from the ethics committee for health research. Patients with a diagnosis of predicted mild acute biliary pancreatitis were divided into Group A (early oral refeeding, EOR) and Group B (usual oral refeeding, UOR). Outcome measures included pancreatic lipase levels, the systemic inflammatory response (concentrations of leukocytes), feasibility (evaluated by abdominal pain recurrence), the presence and recurrence of gastrointestinal symptoms and the length of hospital stay. RESULTS: Two patients in the EOR group experienced pain relapse (3.2%), and four patients in the UOR group experienced pain relapse (6.77%) after oral refeeding (p = 0.379). The presence of nausea or vomiting after the onset of oral refeeding was not different between the two groups (p = 0.293). The onset of oral refeeding was approximately 48 h later in the UOR group. The length of hospital stay was 5 days in the EOR group and 8 days in the UOR group (p = 0.042), and this difference was also manifested in higher hospital costs in the UOR group (p = 0.0235). CONCLUSION: Compared with usual oral refeeding, early oral refeeding is safe in predicted mild acute biliary pancreatitis patients, does not cause adverse gastrointestinal events, and reduces the length of hospital stay and costs. TRIAL REGISTRATION: Early oral refeeding in mild acute pancreatitis (EORVsUOR). NCT04168801 , retrospectively registered (November 19, 2019).

Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1.

Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with Nrf2/Ho-1 expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0-30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the Ho-1 mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including Ho-1 mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of Ho-1 expression.