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Study Objectives: Intrapleural immunotherapy has shown some activity in patients with malignant mesothelioma. We conducted a multicentric pilot phase II study to evaluate the tolerance and the activity of intrapleurally infused autologous human activated macrophages (AM Phi) in patients with stage IA, IB, and IIA malignant pleural mesothelioma (MPM).Design: AM Phi derived from in vitro monocyte culture were infused into the pleura of patients every week for 8 consecutive weeks. Each infusion was followed 3 days later by an intrapleural injection of 9 millions units of gamma-interferon (gamma-IFN) in an attempt to prolong the in vivo activation of infused AM Phi. Response was assessed by CT scan and thoracoscopy when possible. If the patient's disease progressed after AM Phi treatment, an additional treatment was left to the choice of the investigator.Patients: Nineteen patients with histologically proven stage IA, IB, or IIA MPM were enrolled. Two patients were excluded before any AM Phi infusion because of complications impeding infusion. Seventeen patients were actually treated. After completion of the AM Phi cellular therapy, 10 patients were treated with chemotherapy as their diseases progressed.Results: The overall response rate of patients actually treated was 14%. When including the two patients enrolled but not treated, the overall response "in intention to treat" was 11%; two patients had a partial response, with a duration of response of 30 months and 3 months, respectively. One patient, who could not be evaluated by thoracoscopy because of pleural symphysis, is still alive without any clinical or radiologic sign of disease 69 months after treatment. No major adverse effects were observed during the infusion of either AM Phi or gamma-IFN, and there was no interruption of treatment because of toxicity. However, symphysis was observed in 7 of 14 patients who received the complete treatment. The median survival of patients actually treated, including those who received chemotherapy after AM Phi, was 29.2 months.Conclusion: Combined infusion of AM Phi and gamma-IFN was well tolerated in patients with MPM; however, it had limited antitumor activity. [ABSTRACT FROM AUTHOR]

A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8–1.9) for possible exposure and 3.6 (95% CI 2.4–5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8–1.8) for the lowest exposure category to 8.7 (95% CI 4.1–18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1–86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s. Am J Epidemiol 1998; 148: 133–42. [ABSTRACT FROM AUTHOR]

Lipids of human milk or infant formula convey most of the energy necessary to support the newborn growth. Until recently, infant formula chemical composition had been optimized but not their structure. And yet, more and more proofs of evidence have shown that lipids structure in human milk modulates digestion kinetics and is involved in metabolic programming. Indeed there is a striking difference of structure between human milk which is an emulsion based on dispersed milk fat globules (4 μm) secreted by the mammary gland and submicronic neoformed lipid droplets (0.5 μm) found in infant formula. These droplets result from a series of operation units. This difference of structure modifies digestion kinetics and emulsion disintegration in the intestinal tract of the newborn. This difference persists along gastric phase which is mainly dominated by acid and enzyme-induced aggregation. Lipid droplets size is thus the key parameter to control gastric lipolysis and emptying and intestinal lipolysis. This parameter also controls proteolysis since adsorbed proteins are more rapidly hydrolyzed than when in solution. In animal models, these differences of lipid structure would also impact digestive and immune systems' maturation and microbiota. Lipid structure during neonatal period would also be involved in the early programming of adipose tissues and metabolism. The supplementation of infant formulas with bovine milk fractions (milk fat globule membrane extracts, triacylglycerol) or recent development of large droplets infant formula, along with new fields of innovation in neonatal nutrition, are here reviewed.

Milk fat secretion is a complex process that initiates in the endoplasmic reticulum of the mammary epithelial cell by the budding of lipid droplets. Lipid droplets are finally released as fat globules in milk enveloped by the apical plasma membrane of the mammary epithelial cell. The milk fat globule membrane (MFGM) thus comprises membrane-specific proteins and polar lipids (glycerophospholipids and sphingolipids) surrounding a core of neutral lipids (mainly triacylglycerols and cholesterol esters). We have recently described major proteins of the MFGM in the goat and we have highlighted prominent differences between goats and bovine species, especially regarding lactadherin, a major MFGM protein. Here, we show that, in the goat species, the well-documented genetic polymorphism at the as1-casein (CSN1S1) locus affects both structure and composition of milk fat globules. We first evidenced that both milk fat globule size and ζ-potential are related to the as1-casein genotype. At midlactation, goats displaying strong genotypes for as1-casein (A/A goats) produce larger fat globules than goats with a null genotype at the CSN1S1 locus (O/O goats). A linear relationship (R² = 0.75) between fat content (g/ kg) in the milk and diameter of fat globules (µm) was established. Moreover, we found significant differences with regard to MFGM composition (including both polar lipids and MFGM proteins) from goats with extreme genotype at the CSN1S1 locus. At midlactation, the amount of polar lipids is significantly higher in the MFGM from goats with null genotypes for as1-casein (O/O goats; 5.97 ± 0.11 mg/g of fat; mean ± standard deviation) than in the MFGM from goats with strong genotypes for as1-casein (A/A goats; 3.96 ± 0.12 mg/g of fat; mean ± standard deviation). Two MFGM-associated proteins, namely lactadherin and stomatin, are also significantly upregulated in the MFGM from goats with null genotype for as1-casein at early lactation. Our findings are discussed with regard to techno-functional properties and nutritional value of goat milk. In addition, the genetic polymorphism in the goat species appears to be a tool to provide clues to the lipid secretion pathways in the mammary epithelial cell. [ABSTRACT FROM AUTHOR]

The main objective of this study was to assess the ability of the NEar Real Digestive Tract (NERDT), a computer-controlled biomimetic in vitro digestion system that considers the biomechanics of the stomach, to reproduce physiologically relevant features of skimmed milk gastric digestion. A second objective was to evaluate the influence of pepsin on the gastric coagulation and emptying of milk proteins from experiments performed with and without pepsin. A mass balance model over the stomach, assuming a perfectly stirred reactor behaviour, has been developed. The results show that the NERDT can adequately reproduce the targeted kinetics of gastric acidification and emptying, with a sieving effect that naturally leads to a delayed emptying of caseins. Milk coagulated earlier and more chyme was emptied towards the end of the experiments in the presence of pepsin than without, hence illustrating the key influence of pepsin on the gastric coagulation of caseins and subsequent hydrolysis and emptying of dairy particles. Overall, this study shows that the NERDT can be adequately controlled to achieve desired gastric digestion conditions, and appears to be a very useful tool to further improve the knowledge of the gastric digestion behaviour of complex foods such as milk., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fortification of human milk (HM) is often necessary to meet the nutritional requirements of preterm infants. The present experiment aimed to establish whether the supplementation of HM with either an experimental donkey milk-derived fortifier containing whole donkey milk proteins, or with a commercial bovine milk-derived fortifier containing hydrolyzed bovine whey proteins, affects peptide release differently during digestion. The experiment was conducted using an in vitro dynamic system designed to simulate the preterm infant's digestion followed by digesta analysis by means of LC-MS-MS. The different fortifiers did not appear to influence the cumulative intensity of HM peptides. Fortification had a differential impact on the release of either donkey or bovine bioactive peptides. Donkey milk peptides showed antioxidant/ACE inhibitory activities, while bovine peptides showed opioid, dipeptil- and propyl endo- peptidase inhibitory and antimicrobial activity. A slight delay in peptide release from human lactoferrin and α-lactalbumin was observed when HM was supplemented with donkey milk-derived fortifier., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura Cavallarin has patent #Food Composition - EP 3057450 B1 issued to n.a. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

An amaranth beverage (AB) was subjected to a simulated process of dynamic gastrointestinal digestion DIDGI®, a simple two-compartment in vitro dynamic gastrointestinal digestion system. The structural changes caused to the proteins during digestion and the digesta inhibitory capacity of the angiotensin converting enzyme (ACE) were investigated. In gastric compartment the degree of hydrolysis (DH) was 14.7 ± 1.5 % and in the intestinal compartment, proteins were digests in a greater extent (DH = 60.6 ± 8.4 %). Protein aggregation was detected during the gastric phase. The final digesta obtained both at the gastric and intestinal level, showed ACE inhibitory capacity (IC 50 80 ± 10 and 140 ± 20 μg/mL, respectively). Purified fractions from these digesta showed even greater inhibitory capacity, being eluted 2 (E2) the most active fraction (IC 50 60 ± 10 μg/mL). Twenty-six peptide sequences were identified. Six of them, with potential antihypertensive capacity, belong to A. hypochondriacus, 3 agglutinins and 3 encrypted sequences in the 11S globulin. Results obtained provide new and useful information on peptides released from the digestion of an amaranth based beverage and its ACE bioactivity., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Probiotics have gained attention for their potential maintaining gut and immune homeostasis. They have been found to confer protection against pathogen colonization, possess immunomodulatory effects, enhance gut barrier functionality, and mitigate inflammation. However, a thorough understanding of the unique mechanisms of effects triggered by individual strains is necessary to optimize their therapeutic efficacy. Probiogenomics, involving high-throughput techniques, can help identify uncharacterized strains and aid in the rational selection of new probiotics. This study evaluates the potential of the Escherichia coli CEC15 strain as a probiotic through in silico, in vitro, and in vivo analyses, comparing it to the well-known probiotic reference E. coli Nissle 1917. Genomic analysis was conducted to identify traits with potential beneficial activity and to assess the safety of each strain (genomic islands, bacteriocin production, antibiotic resistance, production of proteins involved in host homeostasis, and proteins with adhesive properties). In vitro studies assessed survival in gastrointestinal simulated conditions and adhesion to cultured human intestinal cells. Safety was evaluated in BALB/c mice, monitoring the impact of E. coli consumption on clinical signs, intestinal architecture, intestinal permeability, and fecal microbiota. Additionally, the protective effects of both strains were assessed in a murine model of 5-FU-induced mucositis., Results: CEC15 mitigates inflammation, reinforces intestinal barrier, and modulates intestinal microbiota. In silico analysis revealed fewer pathogenicity-related traits in CEC15, when compared to Nissle 1917, with fewer toxin-associated genes and no gene suggesting the production of colibactin (a genotoxic agent). Most predicted antibiotic-resistance genes were neither associated with actual resistance, nor with transposable elements. The genome of CEC15 strain encodes proteins related to stress tolerance and to adhesion, in line with its better survival during digestion and higher adhesion to intestinal cells, when compared to Nissle 1917. Moreover, CEC15 exhibited beneficial effects on mice and their intestinal microbiota, both in healthy animals and against 5FU-induced intestinal mucositis., Conclusions: These findings suggest that the CEC15 strain holds promise as a probiotic, as it could modulate the intestinal microbiota, providing immunomodulatory and anti-inflammatory effects, and reinforcing the intestinal barrier. These findings may have implications for the treatment of gastrointestinal disorders, particularly some forms of diarrhea., (© 2023. The Author(s).)

Protein digestibility, a key indicator of dietary protein quality for human nutrition, can be estimated using an in vitro digestion model, however its definition and determination remain variable across studies. The present study aimed to determine the contribution of the endogenous nitrogen (N) to the plant and animal protein digestibility values obtained in vitro. 15 N-labelled gluten and caseins (4, 8 and 16 % of the model meal) were used to differentiate dietary and endogenous N and were digested using the INFOGEST in vitro digestion model with no oral phase. The dietary and endogenous N were measured before and during digestion after centrifugation and 10 kDa ultrafiltration. The proteolysis degree was measured by the OPA method. The endogenous and dietary N were determined by elemental analyser coupled with isotopic ratio mass spectrometry. Apparent and true digestibility were determined and values of 135, 92 and 71 % for apparent vs. 78, 69, 60 % for true digestibility were obtained for 4, 8 and 16 % dietary protein level, respectively, with a significant effect of protein level. Differences between apparent and true digestibility pointed out the important contribution of the endogenous nitrogen. Our results showed that 40 % of the N below 10 kDa, i.e., the digestible fraction, were from endogenous origin (i.e. from the pancreatin) and was even present before digestion. An average value of 27 % for pancreatin N autolysis was estimated independently of the protein levels or sources. The use of 15 N-labelled protein to evaluate in vitro protein digestibility highlighted the important contribution of the endogenous N, in particular when low dietary protein solution (4 %) are digested. This gives new keys to overcome drawbacks of in vitro models for determining protein digestibility., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)