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Background: Hematopoietic stem cell transplantation (HSCT) is a procedure with high morbidity and mortality. Identifying patients for maximum benefit and risk assessment is crucial in the decision‐making process. This has led to the development of predictive risk models for HSCT in adults, which have limitations when applied to pediatric population. Our goal was to develop an automatic learning algorithm to predict survival in children with malignant disorders undergoing HSCT. Methods: We studied allogenic HSCTs performed on children with malignant disorders at a third‐level hospital between 1991 and 2021. Survival was analyzed using the Kaplan–Meier method, log‐rank test for the univariate analysis, and Cox regression for the multivariate analysis. A prognostic index was constructed based on these findings. Lastly, we constructed a predictive model using a random forest algorithm to forecast 1‐year survival after HSCT. Results: We analyzed 229 HSCTs in 201 patients with a median follow‐up of 1.64 years. Variables that impacted on the multivariate analysis were older age (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12–1.76, p =.003), oldest period of HSCT (HR 0.46, 95% CI 0.29–0.73, p <.001), and mismatched donor (HR 2.65, 95% CI 1.51–4.65, p =.001). Our prognostic index was associated with 3‐year overall survival (OS; p <.001). A random forest was developed using as variables: diagnosis, age, year of HSCT, time from diagnosis to HSCT, disease stage, donor type, and conditioning. This achieved 72% accuracy in predicting 1‐year OS. Conclusions: Our index and random forest was effective in predicting 1‐year survival. However, further validation in diverse populations is necessary to establish their generalizability. [ABSTRACT FROM AUTHOR]

Milk is a source of bioactive proteins with defensive properties of great value for protecting the newborn. The activity of bovine milk lactoferrin (LF) was investigated as an antibacterial agent in the internalisation of the emergent pathogen Cronobacter sakazakii into Caco-2/TC7 cells, a model of human intestinal epithelium. The effect of LF on oxidative stress and expression of Toll-like receptors (TLR) was also investigated. LF exerted a clear antibacterial activity against C. sakazakii , as well as an inhibitory effect on C. sakazakii adhesion and internalisation into Caco-2/TC7 cells. Incubation with C. sakazakii induced an increase in oxidative stress on the lipid fraction of Caco-2/TC7 cells, which was reversed by LF. Additionally, LF altered the expression of TLR, with a clear decrease in the expression levels of TLR4 at 24 h of incubation. These results suggest that LF has very interesting properties as a potential ingredient for functional foods. [ABSTRACT FROM AUTHOR]

Lactoferrin (LF) is a whey protein with various and valuable biological activities. For this reason, LF has been used as a supplement in formula milk and functional products. However, it must be considered that the properties of LF can be affected by technological treatments and gastrointestinal conditions. In this article, we have revised the literature published on the research done during the last decades on the development of various technologies, such as encapsulation or composite materials, to protect LF and avoid its degradation. Multiple compounds can be used to conduct this protective function, such as proteins, including those from milk, or polysaccharides, like alginate or chitosan. Furthermore, LF can be used as a component in complexes, nanoparticles, hydrogels and emulsions, to encapsulate, protect and deliver other bioactive compounds, such as essential oils or probiotics. Additionally, LF can be part of systems to deliver drugs or to apply certain therapies to target cells expressing LF receptors. These systems also allow improving the detection of gliomas and have also been used for treating some pathologies, such as different types of tumours. Finally, the application of LF in edible and active films can be effective against some contaminants and limit the increase of the natural microbiota present in meat, for example, becoming one of the most interesting research topics in food technology. [ABSTRACT FROM AUTHOR]

Rotaviruses are the leading agents of severe diarrheal disease in infants and young children and complementary strategies to vaccination are needed. Therefore, we evaluated the activity of lactoferrin (LF) from different species against rotavirus in differentiated Caco-2/TC7 cells. The mechanism of rotavirus inhibition and the influence of iron saturation and sialic acid content were also investigated. Furthermore, the effect of bovine LF on Toll-like receptor expression (TLRs) during rotavirus infection was studied. LF presented high inhibitory activity against rotavirus above 8 mg mL−1, the bovine protein being the most potent. The antirotaviral mechanism of LF was mainly related to the virus neutralisation at an early step of infection. Interestingly, a direct relationship between rotavirus neutralisation activity and content of sialic acid in LFs was observed. Finally, the neutralisation of rotavirus by LF leaded to a decreased expression of TLRs in Caco-2/TC7 cells, with a more evident effect on TLR7. [ABSTRACT FROM AUTHOR]

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the generation of anti-DNA autoantibodies due to exposure of immune cells to excessive amounts of extracellular DNA. Lack of P-selectin in mice induces the development of a lupus-like syndrome and patients with cutaneous lupus have reduced P-selectin expression in skin vessels. Using flow cytometry we analyzed in healthy donors and patients the expression of P-selectin Glycoprotein Ligand-1 (PSGL-1) in circulating neutrophils and the implication of PSGL-1/P-selectin interaction in neutrophil extracellular traps (NETs) generation. We found a statistical significance that neutrophils from active SLE patients have a reduced expression of PSGL-1 and low levels of PSGL-1 in neutrophils from SLE patients associated with the presence of anti-dsDNA antibodies, clinical lung involvement, Raynaud's phenomenon, and positive lupus anticoagulant. PSGL-1 is present along the DNA in the NET. In healthy donors, neutrophil interaction with immobilized P-selectin triggers Syk activation, increases the NETs percentage and reduces the amount of DNA extruded in the NETs. In active SLE patients, neutrophil interaction with P-selectin does not activate Syk or reduce the amount of DNA extruded in the NETs, that might contribute to increase the extracellular level of DNA and hence, to disease pathogenesis. [ABSTRACT FROM AUTHOR]

The article presents Comparative effect of bovine buttermilk, whey, and lactoferrin on the innate immunity receptors and oxidative status of intestinal epithelial cells. Topics discussed include Milk contains bioactive molecules with important functions as defensive proteins; among them are the whey protein lactoferrin and proteins of the milk fat globule membrane (MFGM) present in buttermilk; and the aim of this study has been to investigate the effects of lactoferrin, whey, and buttermilk.

Milk contains bioactive molecules with important functions as defensive proteins; among them are the whey protein lactoferrin and proteins of the milk fat globule membrane (MFGM) present in buttermilk. The aim of this study has been to investigate the effects of lactoferrin, whey, and buttermilk as modulators of intestinal innate immunity and oxidative stress on intestinal epithelial cells, to evaluate its potential use for the development of functional foods. The mRNA expression levels of innate immune system Toll-like receptors (TLR2, TLR4, and TLR9), lipid peroxidation (malondialdehyde + 4-hydroxyalkenals) and protein expression levels of carbonyl were analyzed in enterocyte-like Caco-2/TC7 cells treated for 24 h with different concentrations of lactoferrin, whey, or buttermilk. None of the substances analyzed caused oxidative damage; however, whey significantly decreased the levels of lipid peroxidation. Furthermore, both lactoferrin and whey reduced the oxidative stress induced by lipopolysaccharide. With respect to TLR receptors, lactoferrin, whey, and buttermilk specifically altered the expression of TLR2, TLR4, and TLR9 receptors, with a strong decrease in the expression levels of TLR4. These results suggest that lactoferrin, whey, and buttermilk are potentially interesting ingredients for functional foods because they seem to modulate oxidative stress and the inflammatory response induced by the activation of TLRs. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin (bLF) is an iron-binding glycoprotein used in functional and therapeutic products due to its biological properties, the most important being its antimicrobial activity. In this study, hydrolysates of bovine lactoferrin (bLFH) obtained with pepsin, chymosin and microbial rennet were assayed against Cronobacter sakazakii (104 CFU/mL) in different media: phosphate buffered saline (PBS), bovine skim milk and whey, and reconstituted powdered infant formula (PIFM). The results obtained have shown that hydrolysis of bLF enhances its antibacterial activity against C. sakazakii. The three types of bLFH dissolved in PBS reduced C. sakazakii growth from a concentration of 0.1 mg/mL and inhibited it completely above 0.5 mg/mL, after 4 and 8 h of incubation at 37 °C. The three bLFH (1 and 2 mg/mL) did not show any antibacterial activity in skim milk, whey and reconstituted PIFM after 8 h of incubation at 37 °C. However, C. sakazakii growth was completely inhibited in whey when pepsin and chymosin bLFH (2 mg/mL) were combined with undigested bLF (2 mg/mL), after 8 h of incubation at 37 °C. On the other hand, the combination of any of the three hydrolysates with bLF showed very low activity in skim milk and practically no activity in reconstituted PIFM. Furthermore, the effect of temperature after reconstitution (4, 23 and 37 °C), on the antibacterial activity of bLF (2.5 and 5 mg/mL) in reconstituted PIFM contaminated with C. sakazakii (10–102 CFU/mL) was also investigated. bLF at 5 mg/mL significantly reduced (p <.05) the proliferation of C. sakazakii in reconstituted PIFM at 37 °C until 2 h. C. sakazakii did not grow at 4 °C for 6 days in reconstituted PIFM with or without bLF. The effect of microwave heating (450, 550 and 650 W for 5, 10 and 15 s) on the antibacterial activity and stability of bLF (2.5 mg/mL) in reconstituted PIFM contaminated with C. sakazakii (10–102 CFU/mL) was also studied. The antibacterial activity of bLF was maintained after treatments at 450 and 550 W for 5 s, which kept 94 and 89% of bLF immunoreactivity, respectively. Moreover, microwave treatments of reconstituted PIFM with or without bLF, at 650 W for 5 s, and at 450, 550 and 650 W for 10 and 15 s, completely inactivated C. sakazakii. • Hydrolysis of bovine lactoferrin enhances inhibitory activity a gainst C. sakazakii. • Hydrolysates are more active in whey when combined with intact lactoferrin. • Lactoferrin can control C. sakazakii growth in infant formula kept at 37 °C or 23 °C. • Activity of lactoferrin was maintained in formula after low microwave treatments. [ABSTRACT FROM AUTHOR]