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Bacterial infections have become a global concern, stimulating the growing demand for natural and biologically safe therapeutic agents with antibacterial action. This study was evaluated the genotoxicity of the trypsin inhibitor isolated from tamarind seeds (TTI) and the antibacterial effect of TTI theoric model, number 56, and conformation number 287 (TTIp 56/287) and derived peptides in silico . TTI (0.3 and 0.6 mg.mL -1 ) did not cause genotoxicity in cells ( p  > 0.05). In silico , a greater interaction of TTIp 56/287 with the Gram-positive membrane (GP) was observed, with an interaction potential energy (IPE) of -1094.97 kcal.mol -1 . In the TTIp 56/287-GP interaction, the Arginine, Threonine (Thr), and Lysine residues presented lower IPE. In molecular dynamics (MD), Peptidotrychyme59 (TVSQTPIDIPIGLPVR) showed an IPE of -518.08 kcal.mol -1 with the membrane of GP bacteria, and the Thr and Arginine residues showed the greater IPE. The results highlight new perspectives on TTI and its derived peptides antibacterial activity.

The study aimed to prospect in silico native and analogous peptides with anti-SARS-CoV-2 potential derived from the trypsin inhibitor purified from tamarind seeds (TTIp). From the most stable theoretical model of TTIp (TTIp 56/287), in silico cleavage was performed for the theoretical identification of native peptides and generation of analogous peptides. The anti-SARS-CoV-2 potential was investigated through molecular dynamics (MD) simulation between the peptides and binding sites of transmembrane serine protease 2 (TMPRSS2), responsible for the entry of SARS-CoV-2 into the host cell. Five native and analogous peptides were obtained and validated through chemical and physical parameters. The best interaction potential energy (IPE) occurred between TMPRSS2 and one of the native peptides obtained by cleavage with trypsin and its analogous peptide. Thus, both peptides showed many hydrophobic residues, a common physical-chemical property among the peptides that inhibit the entry of enveloped viruses, such as SARS-CoV-2, present in specific drugs to treat COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The study evaluated the effect of the carotenoid-rich extract from cantaloupe melon (CE) nanoencapsulated in porcine gelatin (EPG) on hepatic retinol concentration and liver damage scores in Wistar rats with obesity induced by high glycemic index and high glycemic load diet (HGLI diet). For 17 days, animals were fed the HGLI diet. They were divided into three groups and treated for 10 days [HGLI diet + water, HGLI diet + CE (12.5 mg/kg), and HGLI diet + EPG (50 mg/kg)]. The groups were evaluated for dietary intake, retinol, weight variation, hematological parameters, fasting glucose, lipid profile, hepatic retinol concentration, AST/ALT ratio, FIB-4 (Fibrosis-4 Index for Liver Fibrosis), and APRI (AST to Platelet Ratio Index) scores to evaluate the effects on the liver. Animals treated with EPG showed a lower dietary intake ( p < 0.05). No significant weight change was detected in the evaluated groups ( p > 0.05). The EPG-treated group had significantly higher concentrations ( p < 0.05) of hepatic retinol [266 (45) μg/g] than the untreated group [186 (23.8) μg/g] and the one treated with CE [175 (8.08) μg/g]. Liver damage assessment scores did not show significant differences, but the lowest means were observed in the group treated with EPG. The nanoencapsulation of the extract rich in beta-carotene promoted reduced food consumption and increased hepatic retinol without causing significant changes in liver damage scores. Thus, EPG is a candidate for future clinical studies to evaluate the beneficial effects of treating diseases involving vitamin A deficiencies., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Several studies in animal models of intestinal inflammation have been performed with the aim of understanding the mechanisms of action of anti-inflammatory proteins and peptides that reduce TNF-α. In order to present the best targets, effects and strategies for the treatment of intestinal inflammation in experimental models, this systematic review (SR) aimed to answer the following question: what are the mechanisms of action of molecules with anti-TNF-α activity on the intestinal barrier? The SR protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, number CRD42019131862) and guided by the methodological procedures used for the elaboration of the SR. Articles that were part of the SR were selected considering the eligibility criteria according to the PICO (Population, Intervention, Comparison/Control and Outcomes) and were searched in the PubMed, Scopus, Web of Science, Excerpta Medica Database (EMBASE) and ScienceDirect databases. Twenty-five articles reporting studies in rats and mice were selected and the risk of bias was assessed using the tool from the SYstematic Review Center for Laboratory Animal Experimentation (SYRCLE). A descriptive synthesis of the results obtained was carried out. Based on the results, the anti-inflammatory molecules that reduced TNF-α acted mainly on the TNF-TNFR1/TNFR2 and TLR4/MD2 complex signaling pathways, and consequently on the NF-κB pathway. This improved the aspects of the inflammatory diseases studied. In addition, these mechanisms also improved the macroscopic, histological and permeability aspects in the intestine of the animals. These findings point to the potential of protein and peptide molecules that act on inflammatory pathways for medical applications with specific and promising strategic targets, aiming to improve inflammatory diseases that affect the intestine. This systematic review also highlights the need for more details during the methodological description of preclinical studies, since this was a limitation found., Competing Interests: the authors have declared that no competing interests exist.

Background: Tumor necrosis factor-alpha (TNF-alpha), among cytokines that mediate the inflammatory process, plays an important role in diseases involving the loss of intestinal barrier integrity. Several molecules with anti-TNF-alpha activity have been studied aiming to develop new therapies. The purpose of this paper is to describe the systematic review protocol of experimental studies that determine mechanisms of action of molecules with anti-TNF-alpha activity on intestinal barrier inflammation., Methods: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P). The databases to be searched are PubMed, EMBASE, Scopus, ScienceDirect, and Web of Science. Experimental studies in rats or mice that assessed the activity of anti-TNF-alpha molecules in models of intestinal barrier inflammation will be included in the systematic review. Studies characteristics, experimental model, and main results will be described and the bias risk assessment will be performed. Two independent reviewers will perform study selection, data extraction, and methodological quality assessment. A narrative synthesis will be made for the included studies. Also, if sufficient data is available, a meta-analysis will be conducted. I statistics will be used to assess heterogeneity., Results: The present protocol will assist in producing a systematic review that identifies the mechanisms underlying the reduction of TNF-alpha in intestinal barrier inflammation models., Conclusion: The systematic review may contribute to the theoretical basis of research on new molecules with anti-TNF-alpha potential and, consequently, in the development of new therapies employed in humans., Prospero Registration Number: CRD42019131862.

Objective: To determine the concentration of alpha-tocopherol in umbilical cord serum of full-term and preterm newborns, in order to assess the nutritional status of both groups in relation to the vitamin and its possible correlation with intrauterine growth., Methods: A cross-sectional observational study conducted with 140 newborns, of which 64 were preterm and 76 were full-term. They did not have any malformations, they came from healthy mothers, who were nonsmokers, and delivered a single baby. Intrauterine growth was evaluated by weight-to-gestational age at birth, using Intergrowth-21st. Thealpha-tocopherol levels of umbilical cord serum were analyzed by High Performance Liquid Chromatography., Results: The mean concentration of alpha-tocopherol in umbilical cord serum for preterm and full-term infants was 263.3±129.5 and 247.0±147.6 µg/dL (p=0.494). In the preterm group, 23% were small for gestational age, whereas in the full-term group, this percentage was only 7% (p=0.017). Low levels of vitamin E were found in 95.3% of preterm infants and 92.1% of full-term infants. There was no correlation between alpha-tocopherol levels and weight to gestational age Z score (p=0.951)., Conclusions: No association was found between alpha-tocopherol levels and weight to gestational age at birth. Intrauterine growth restriction was more frequent in preterm infants and most infants had low levels of vitamin E at the time of delivery.

Objectives: To determine the alpha-tocopherol concentration in breast milk at different periods of lactation and to estimate the possible supply of vitamin E to the infant., Methods: A longitudinal observational study was carried out with 100 mothers at University Hospital Ana Bezerra (HUAB), at Universidade Federal do Rio Grande do Norte, in Santa Cruz (RN), Northeast Brazil. Samples of colostrum (n=100), transitional milk (n=77), and mature milk (n=63) were collected. Alpha-tocopherol was analyzed by high-performance liquid chromatography. Vitamin supply to the newborn was estimated by comparing the nutritional requirement of vitamin E (4 mg/day) with the potential daily intake of milk., Results: The mean alpha-tocopherol concentration found in colostrum, transitional, and mature milk was 40.5±15.0 µmol/L, 13.9±5.2 µmol/L, and 8.0±3.8 µmol/L, respectively (p<0.001). The possible effect of these milks offered to the infant 6.2 mg/day of vitamin E in colostrum, 4.7 mg/day in transitional milk, and 2.7 mg/day in mature milk (p<0.0001), shows that only the mature milk did not guarantee the recommended quantity of this vitamin., Conclusions: Alpha-tocopherol levels in human milk decrease through the progression of lactation, and the possible intake of colostrum and transitional milk met the nutritional requirement of the infant. Mature milk may provide smaller amounts of vitamin E. Thus, it is important to study the factors that are associated with such low levels.

Background: Preterm newborns have low vitamin A reserves at birth, which increases their risk of morbidity and mortality. In the absence of supplementation, breast milk is the only source of this nutrient for exclusively breastfed infants., Aims: To assess retinol concentration in preterm milk and the relationship between this retinol concentration and lactation phase, degree of prematurity, and maternal serum retinol level., Study Design: Longitudinal study., Subjects: Fifty-eight preterm mothers., Outcome Measures: Colostrum (1-3d), transitional (7-15d), and mature human milk (30-55d) samples were collected. Maternal blood was collected once at postpartum. Retinol level was measured using high-performance liquid chromatography., Results: Milk retinol concentration was statistically different between lactation phases (p<0.001): 2.84±1.05μmol/L in colostrum (58), 3.47±1.28μmol/L in transitional (58), and 2.03±0.61μmol/L in mature milk (30). No difference was found in milk retinol levels between groups with different degrees of prematurity (p>0.05). Maternal serum retinol (1.82±0.50μmol/L) did not correlate with milk levels (p>0.05)., Conclusions: Retinol level in preterm milk seems to be independent of the degree of prematurity and maternal serum status. A significant increase in micronutrient levels in transitional milk was observed, which is likely to contribute to reserves in the premature liver., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Vitamin E is important because of its antioxidant activity in situations of oxidative stress, especially postnatally. Hence, the objective was to verify whether maternal alpha-tocopherol level is associated with the alpha-tocopherol levels of the newborn and colostrum. This is a cross-sectional study of 58 women and their term newborns from a public hospital. Blood and colostrum were collected to measure alpha-tocopherol levels by high-performance liquid chromatography. Mothers with serum alpha-tocopherol levels <16.2 mmol L(-1) and newborns <11.6 mmol L(-1) were indicative of deficiency or low levels. Mothers were divided into two groups: <16.2 mmol L(-1) and those with levels ≥16.2 mmol L(-1) . The mean (95% confidence interval) serum alpha-tocopherol levels of mothers, umbilical cords and colostrum were 28 (24-32), 6 (5-8) and 39 mmol L(-1) (32-45), respectively (P < 0.001); 19% of the women and 90% of the newborns had low alpha-tocopherol levels. Maternal alpha-tocopherol level was associated with that of the umbilical cord. Newborns from mothers at risk of deficiency had low alpha-tocopherol levels (P < 0.001). Colostrum levels of vitamin E were not influenced by maternal serum. Maternal deficiency influenced the vitamin E level of the umbilical cord but does not in the colostrum, evidencing distinct transfer mechanisms via the mammary gland., (© 2016 John Wiley & Sons Ltd.)

We evaluated the effect of maternal vitamin E supplementation on the α-tocopherol concentrations of colostrum, transitional milk and mature milk of women who had given birth prematurely. This longitudinal randomised-controlled trial divided eighty-nine women into two groups: a control group and a supplemented group. Blood and breast milk were collected from all the participants after delivery. Next, each woman in the supplemented group received 400 IU of RRR-α-tocopheryl acetate. Further breast milk samples were collected 24 h after the first collection, as well as 7 and 30 d after delivery. α-Tocopherol concentrations were determined by HPLC. The baseline α-tocopherol concentrations in the maternal serum of the two groups were similar: 1159·8 (sd 292·4) μg/dl (27·0 (SD 6·8) μmol/l) for the control group and 1128·3 (sd 407·2) μg/dl (26·2 (SD 9·5) μmol/l) for the supplemented group. None of the women was vitamin E deficient. Breast milk α-tocopherol concentrations increased by 60 % 24 h after supplementation in the intervention group and did not increase at all in the control group. α-Tocopherol concentration of the transitional milk in the supplemented group was 35 % higher compared with the control group. α-Tocopherol concentrations of the mature milk in both groups were similar. Maternal supplementation with 400 IU of RRR-α-tocopherol increased the vitamin E concentrations of the colostrum and transitional milk, but not of the mature milk. This study presents relevant information for the design of strategies to prevent and combat vitamin E deficiency in the risk group of preterm infants.

Objective: The aim of the study was to evaluate and compare the levels of alpha-tocopherol in colostrum milk and serum of mothers with premature birth, classified as severe prematurity and moderate prematurity., Methods: Cross-sectional study with 65 women, 18 births classified as severe prematurity (<32 weeks of gestation) and 47 as moderate prematurity (≥32 weeks of gestation). The study only included mothers without any conditions associated with pregnancy and who had a single conception without any malformation. Samples of serum and colostrum were collected during fasting in the immediate postpartum, and alpha-tocopherol was analyzed by high-performance liquid chromatography. To determine the biochemical nutritional status of vitamin E, a serum cutoff (11.6 μmol/L) was adopted. The Student t test for independent variables compared the average concentrations of alpha-tocopherol in serum and colostrum among prematurity groups. Differences were considered significant when P < 0.05., Results: The alpha-tocopherol concentrations in colostrum were similar in both groups, being 34.5 ± 20.2 μmol/L for women with severe prematurity and 35.1 ± 16.3 μmol/L for moderate prematurity. For the serum of puerperal women with severe prematurity, alpha-tocopherol concentration was, however, lower than in women with moderate prematurity, 22.2 ± 4.4 μmol/L versus 27.1 ± 8.6 μmol/L (P < 0.05). The serum levels of alpha-tocopherol indicated nutritional risk at 5.6% (n = 1) of women with severe prematurity and 4.3% (n = 2) for those with moderate prematurity., Conclusions: Severe prematurity affected the levels of alpha-tocopherol in maternal serum; however, the level of prematurity did not change the concentration of vitamin E in colostrum.

The adequate supply of vitamins A and E to newborns is essential. However, factors such as maternal nutritional status and nutrient interaction may limit its bioavailability. The aim of this study was to establish nutritional status for vitamins A and E and evaluate the correlation of retinol on colostrum alpha-tocopherol in lactating women. A total of 103 lactating women were recruited at a Brazilian public maternity hospital. Fasting serum and colostrum samples were collected in the immediate post-partum. Retinol and alpha-tocopherol levels were determined by high-performance liquid chromatography and nutritional status for these vitamins was defined from specific cut-off points for serum and colostrum. Mean serum and colostrum retinol (1.49 µmol L(-1) , 2.18 µmol L(-1) ) and alpha-tocopherol (26.4 µmol L(-1) , 26.1 µmol L(-1) ) indicated satisfactory biochemical status. However, we found a prevalence of subclinical deficiency of vitamin A and vitamin E in serum (15.5% and 16%) and colostrum (50% and 60%). Lactating women with serum retinol ≥ 1.05 µmol L(-1) showed an inverse correlation between serum retinol and alpha-tocopherol concentration in the colostrum (P = 0.008, r = -0.28). This association was not observed in serum level < 1.05 µmol L(-1) . The nutritional status of lactating women for vitamins A and E was adequate, although there is a risk of subclinical deficiency. The negative correlation of serum retinol on alpha-tocopherol concentration in the colostrum must be carefully evaluated in situations of vitamin A supplementation, because alpha-tocopherol bioavailability in maternal milk may be compromised., (© 2011 Blackwell Publishing Ltd.)

Purpose: To determine the nutritional status of vitamin E in breastfeeding women through the analysis of alpha-tocopherol concentration in serum and colostrum, to analyze its relation with maternal variables and to determine the prevalence of vitamin E deficiency in these women., Methods: The study included 103 mothers who were classified according to maternal variables: age, nutritional status before pregnancy, gestational weight gain, parity and mode of delivery. Colostrum and serum samples were collected under fasting conditions in the immediate postpartum period. Alpha-tocopherol was analyzed by high performance liquid chromatography (HPLC). A serum cutoff of 697.7 μg/dL was adopted to define the nutritional status of vitamin E. Statistical analysis was performed with the Student's t test for independent samples and Pearson's correlation. Differences were significant when p<0.05., Results: The average concentration of alpha-tocopherol was 1.125±551.0 μg/dL in colostrum and 1,138.6±346.0 μg/dL in serum, indicating adequate biochemical nutritional status. However, when analyzing the mothers individually, a 16% rate of subclinical vitamin E deficiency was detected. Women undergoing cesarean delivery had significantly higher alpha-tocopherol levels in colostrum (1.280±591 μg/dL) compared with those undergoing normal delivery (961.7±370 μg/dL) (p<0.05). It was found that mothers who were overweight before pregnancy had higher vitamin concentration in colostrum (1,331.5±548 μg/dL) when compared to underweight women (982.1±374 μg/dL) or women of normal weight (992.3±346 μg/dL) (p<0.05). However, the other variables were not associated with alpha-tocopherol in colostrum. Moreover, no variable showed association with vitamin E levels in maternal serum and no correlation was demonstrated between the alpha-tocopherol levels in serum and in milk., Conclusions: Despite the diagnosis of satisfactory nutritional status, breastfeeding women showed significant risk of subclinical vitamin E deficiency. We suggest that the concentration of alpha-tocopherol in colostrum be associated with type of delivery and pre-gestational nutritional status of women.