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With a growing global population and ageing demographics, the food industry stands at a pivotal crossroads, necessitating bespoke solutions and groundbreaking innovations. In vitro experiments can help understanding food oral processing and formulating products meeting the specific needs of different populations. However, current in vitro models do not reproduce well human oral anatomy and tongue biomechanics, essential for assessing the behaviour of novel and texturized foods under physiologically relevant oral conditions. In response, we unveil a novel 3D biomimetic artificial mouth, showcasing a pneumatic multi-degree-of-freedom artificial tongue meticulously crafted to mirror the mechanical properties and wettability of the human tongue. This cutting-edge technology, featuring tongue surface papillae, is capable of performing lifelike movements. The comparison with in vivo data demonstrates that it accurately reproduces oral processing of three, vastly different, soft foods. Textural characteristics (firmness, adhesive and cohesive properties) and shear viscosities-measured at oral and oropharyngeal-relevant shear rates-of in vitro food boli closely mirrored those observed in vivo. This in vitro device presents unprecedented opportunities for studying the dynamics of food transformation in the mouth, to adapt texture towards food that can be swallowed with ease and to improve food palatability, accommodating specific health needs critical for older adults (e.g., reduced salivary secretion, tongue weakness or poor coordination)., (© 2024. The Author(s).)

Sphaeropsidins are iso-pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown to counteract regulatory volume increase, a process used by cancer cells to avoid apoptosis. This study reports the hemi-synthesis of new lipophilic derivatives obtained by modifications of the C15,C16-alkene moiety. Several of these compounds triggered severe ER swelling associated with strong proteasomal inhibition and consequently cell death, a feature that was not observed with respect to mode of action of the natural product. Significantly, an analysis from the National Cancer Institute sixty cell line testing did not reveal any correlations between the most potent derivative and any other compound in the database, except at high concentrations (LC 50 ). This study led to the discovery of a new set of sphaeropsidin derivatives that may be exploited as potential anti-cancer agents, notably due to their maintained activity towards multidrug resistant models., (© 2024. The Author(s).)

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John's wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care., (© 2022. The Author(s).)

Background: Potentially, orally administered antibodies specific to enteric pathogens could be administered to infants to prevent diarrheal infections, particularly in developing countries where diarrhea is a major problem. However, to prevent infection, such antibodies would need to resist degradation within the gastrointestinal tract., Methods: Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used in this study as a model for examining the digestion of neutralizing antibodies to enteric pathogens in infants. The survival of this recombinant IgG1 across digestion in 11 infants was assayed via an anti-idiotype ELISA and RSV F protein-specific ELISA. Concentrations were controlled for any dilution or concentration that occurred in the digestive system using mass spectrometry-based quantification of co-administered, orally supplemented, indigestible polyethylene glycol (PEG-28)., Results: Binding activity of Palivizumab IgG1 decreased (26-99%) across each phase of in vivo digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs., Conclusion: Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective., Impact: Binding activity of palivizumab IgG1 decreased (26-99%) across each phase of in vivo infant digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. Palivizumab was likely degraded by proteases and changes in pH introduced in the gut. Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. The monoclonal antibody IgG1 tested was not stable across the infant gastrointestinal tract. The observation of palivizumab reduction was unlikely due to dilution in the gastrointestinal tract. The results of this work hint that provision of antibody could be effective in preventing enteric pathogen infection in infants. Orally delivered recombinant antibodies will need to either be dosed at high levels to compensate for digestive losses or be engineered to better resist digestion. Provision of enteric pathogen-specific recombinant antibodies to at-risk infants could provide a new and previously unexplored pathway to reducing the infection in infants. The strategy of enteric recombinant antibodies deserves more investigation throughout medicine as a novel means for treatment of enteric disease targets., (© 2020. International Pediatric Research Foundation, Inc.)

Objective: The influence of previous viral symptoms on the level and duration of human milk antibodies reactive to SARS-CoV-2, and common human coronaviruses (HCoVs) was investigated., Study Design: Antibodies reactive to S1 and S2 subunits from SARS-CoV-2, HCoV-OC43, and HCoV-229E were measured via ELISA in human milk samples collected from March to June 2020 in mothers with and without viral symptoms., Results: The presence of viral symptoms influenced the levels of SARS-CoV-2 S2-reactive SIgA/IgA and tended to influence SARS-CoV-2 S1 SIgA/IgA and S2-reactive SIgM/IgM in human milk but did not relate to IgG. HCoV-229E S1 + S2-reactive SIgA/IgA and SIgM/IgM, as well as HCoV-OC43 S1 + S2-reactive IgG were related to the symptoms. The duration of antibody levels in human milk in mothers with viral symptoms varied between 3 and 4 months post maternal report of viral symptoms., Conclusion: Previous viral symptoms and individual mothers may change the antibody cross-reactive levels to SARS-CoV-2 and HCoVs in human milk.

Objective: This study investigated the impact of probiotic supplementation on the gene expressions of cluster of differentiation (CD) as cell markers and the concentrations of antibodies and cytokines in human milk., Study Design: Gene expressions of CD28, CD19, and CD38 were determined in milk from 15 women ingesting daily probiotics (from Greek yogurt) and 12 women who do not consume probiotics. Concentrations of antibodies and cytokines were measured using ELISA., Results: Gene expression of CD28 tended to be higher in milk from mothers ingesting daily probiotics than mothers who did not take probiotics. Interleukin-6 (IL-6) concentration in milk was higher in mothers ingesting probiotics than those who do not consume probiotics. The increase of IL-6 level in human milk was positively correlated with total IgA and IgG concentrations., Conclusions: Probiotic supplementation could enhance the secretion of IL-6 in human milk. Human milk IL-6 may improve neonatal immunity due to its stimulation of total IgA and IgG.

Objective: This study evaluated the presence and the levels of antibodies reactive to SARS-CoV-2 S1 and S2 subunits (S1 + S2), and nucleocapsid protein., Study Design: The levels of SARS-CoV-2 S1 + S2- and nucleocapsid-reactive SIgM/IgM, IgG and SIgA/IgA were measured in human milk samples from 41 women during the COVID-19 pandemic (2020-HM) and from 16 women 2 years prior to the outbreak (2018-HM)., Results: SARS-CoV-2 S1 + S2-reactive SIgA/IgA, SIgM/IgM and IgG were detected in 97.6%, 68.3% and 58.5% in human milk whereas nucleocapsid-reactive antibodies were detected in 56.4%, 87.2% and 46.2%, respectively. S1 + S2-reactive IgG was higher in milk from women that had symptoms of viral respiratory infection(s) during the last year than in milk from women without symptom. S1 + S2- and nucleocapsid-reactive IgG were higher in the 2020-HM group compared to the 2018-HM group., Conclusions: The presence of SARS-CoV-2-reactive antibodies in human milk could provide passive immunity to breastfed infants and protect them against COVID-19 diseases.

Background: The survival of antibody isotypes specific to pertussis toxin (PT) and filamentous hemagglutinin (FHA) from mother's own milk (MBM) and donor breast milk (DBM) during preterm infant digestion was investigated., Methods: Feed, gastric, and stool samples were collected from 20 preterm mother-infant pairs at 8-9 days and 21-22 days postpartum. Samples were analyzed via ELISA for anti-FHA or anti-PT immunoglobulin A (IgA), IgM, and IgG., Results: Anti-PT IgA, anti-FHA IgG, and anti-PT IgG were lower in MBM than DBM at 8-9 days postpartum, whereas anti-FHA IgM was higher in MBM than DBM. Anti-PT IgA, anti-PT IgG, and anti-FHA IgG in DBM decreased in gastric contents at both postpartum times but those antibodies in MBM were stable or increased during gastric digestion. Anti-FHA-specific IgA and IgM were higher in gastric contents from infants fed MBM than from infants fed DBM at 8-9 days. All pertussis antibodies were detected in infant stools at both postpartum times., Conclusions: Pertussis-specific antibodies from MBM were stable during infant digestion, whereas anti-pertussis IgA and IgG from DBM decreased in gastric contents. The constant region and variable region of antibodies and maternal immunization appear to be the critical factors for their stability to proteolytic digestion and pasteurization., Impact: Pertussis-specific antibodies from mother's breast milk were stable during infant digestion, whereas anti-pertussis IgA and IgG from donor breast milk decreased in gastric contents. The constant region and variable region of pertussis-specific antibodies and the maternal immunization (previous infections and vaccinations) appear to be the critical factors for their stability to proteolytic digestion and pasteurization. Pertussis-specific antibodies from either mother's breast milk or donor breast milk survived during preterm infant digestion and both types of milk will compensate for the lower IgG transplacental transfer in preterm infants compared with term infants.

Background: Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated., Methods: Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA., Results: Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors., Conclusion: This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk., Impact: Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk. Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion. Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

Objective: This study aimed to determine whether vaccination during pregnancy, prematurity, and staphylococci concentration influenced the presence of B. cereus or staphylococcal enterotoxins (SEs) in raw human milk from healthy mothers., Study Design: Human milk samples were collected from 152 healthy women. B. cereus, S. aureus and coagulase-negative staphylococci (CNS) were enumerated using selective agar culture media. The detection of B. cereus spores and SEs were determined using ELISA., Results: CNS and B. cereus concentrations in milk from non-vaccinated mothers were higher than that from mothers vaccinated during pregnancy, but S. aureus did not differ. Prematurity did not affect B. cereus or staphylococci in human milk. S. aureus and CNS concentrations in human milk with the presence of B. cereus were higher than that with the absence of B. cereus. Viable B. cereus was present in 9.2% of raw human milk samples whereas SEs were not detected in any samples., Conclusions: Vaccination during pregnancy and low concentration of staphylococci could reduce the risk of B. cereus in raw human milk. The screening of B. cereus in raw human milk must be performed before pasteurization to reduce the risk of B. cereus infection in preterm infants.

In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages' polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy.