Targeted application of functional foods as immune fitness boosters in the defense against viral infection

In recent times, the emergence of viral infections, including the SARS-CoV-2 virus, the monkeypox virus, and, most recently, the Langya virus, has highlighted the devastating effects of viral infection on human life. There has been significant progress in the development of efficacious vaccines for the prevention and control of viruses; however, the high rates of viral mutation and transmission necessitate the need for novel methods of control, management, and prevention. In recent years, there has been a shift in public awareness on health and wellbeing, with consumers making significant dietary changes to improve their immunity and overall health. This rising health awareness is driving a global increase in the consumption of functional foods. This review delves into the benefits of functional foods as potential natural means to modulate the host immune system to enhance defense against viral infections. We provide an overview of the functional food market in Europe and discuss the benefits of enhancing immune fitness in high-risk groups, including the elderly, those with obesity, and people with underlying chronic conditions. We also discuss the immunomodulatory mechanisms of key functional foods, including dairy proteins and hydrolysates, plant-based functional foods, fermentates, and foods enriched with vitamin D, zinc, and selenium. Our findings reveal four key immunity boosting mechanisms by functional foods, including inhibition of viral proliferation and binding to host cells, modulation of the innate immune response in macrophages and dendritic cells, enhancement of specific immune responses in T cells and B cells, and promotion of the intestinal barrier function. Overall, this review demonstrates that diet-derived nutrients and functional foods show immense potential to boost viral immunity in high-risk individuals and can be an important approach to improving overall immune health

Protein hydrolysates from quinoa (Chenopodium quinoa Willd.) modulate macrophage polarization and the expression of surface antigen molecules

Quinoa (Chenopodium quinoa Willd.) is considered an exceptional source of high‐quality protein and may be a good precursor of bioactive components with immunomodulatory effects. Quinoa protein‐enriched fraction (QPF) was isolated from quinoa seeds via alkaline extraction and isoelectric point precipitation and hydrolyzed at the optimum temperature and pH of two food‐grade proteases to produce QPF hydrolysates (QPFH). SDS‐PAGE and LC–MS analyses showed that low‐molecular weight peptides were present in hydrolyzed proteins and that the enzymes effectively hydrolyzed high‐molecular weight proteins evidenced by significantly higher amino acid levels in QPFH. J774A.1 macrophages and mouse bone‐marrow‐derived macrophages (BMDMs) were polarized into an M1‐like (pro‐inflammatory) or M2‐like (anti‐inflammatory) state in the absence or presence of QPF or QPFH. Our results showed that QPFH attenuated M1‐like response as demonstrated by a significantly lowered secretion of pro‐inflammatory cytokines (IL‐6, TNF‐α, IL‐12p40, and IL‐27p28) and nitric oxide (NO) levels. Co‐treatment with QPFH significantly boosted IL‐10 and arginase activity in both M1‐like and M2‐like cells indicating that the samples may promote a phenotypic switch to M2‐like macrophages. Furthermore, QPFH inhibited pro‐inflammatory cytokines in Loxoribine (LOX)‐activated bone marrow‐derived dendritic cells (BMDCs) and inhibited the same cytokines during a 7‐day DC maturation experiment. QPF but not the QPFH influenced the expression of surface antigen molecules in macrophages by decreasing the frequency of MHCI and CD86 expressing cells. Taken together, these findings reveal novel mechanisms that demonstrate the potential of quinoa protein hydrolysates in the development of immunomodulatory functional foods

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

Gut symbionts Lactobacillus reuteri R2lc and 2010 encode a polyketide synthase cluster that activates the mammalian aryl hydrocarbon receptor

A mechanistic understanding of microbe-host interactions is critical to developing therapeutic strategies for targeted modulation of the host immune system. Different members of the gut symbiont species Lactobacillus reuteri modulate host health by, for example, reduction of intestinal inflammation. Previously, it was shown that L. reuteri activates the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that plays an important role in the mucosal immune system, by the production of tryptophan catabolites. Here, we identified a novel pathway by which L. reuteri activates AhR, which is independent of tryptophan metabolism. We screened a library of 36 L. reuteri strains and determined that R2lc and 2010, strains with a pigmented phenotype, are potent AhR activators. By whole-genome sequencing and comparative genomics, we identified genes unique to R2lc and 2010. Our analyses demonstrated that R2lc harbors two genetically distinct polyketide synthase (PKS) clusters, functionally unknown (fun) and pks, each carried by a multicopy plasmid. Inactivation of pks, but not fun, abolished the ability of R2lc to activate AhR. L. reuteri 2010 has a gene cluster homologous to the pks cluster in R2lc with an identical gene organization, which is also responsible for AhR activation. In conclusion, we identified a novel PKS pathway in L. reuteri R2lc and 2010 that is responsible for AhR activation

A secondary metabolite drives intraspecies antagonism in a gut symbiont that is inhibited by cell-wall acetylation

The mammalian microbiome encodes numerous secondary metabolite biosynthetic gene clusters; yet, their role in microbe-microbe interactions is unclear. Here, we characterized two polyketide synthase gene clusters (fun and pks) in the gut symbiont Limosilactobacillus reuteri. The pks, but not the fun, cluster encodes antimicrobial activity. Forty-one of 51 L. reuteri strains tested are sensitive to Pks products; this finding was independent of strains’ host origin. Sensitivity to Pks was also established in intraspecies competition experiments in gnotobiotic mice. Comparative genome analyses between Pks-resistant and -sensitive strains identified an acyltransferase gene (act) unique to Pks-resistant strains. Subsequent cell-wall analysis of wild-type and act mutant strains showed that Act acetylates cell-wall components, providing resistance to Pks-mediated killing. Additionally, pks mutants lost their competitive advantage, while act mutants lost their Pks resistance in in vivo competition assays. These findings provide insight into how closely related gut symbionts can compete and co-exist in the gastrointestinal tract

Redox regulation of immunity and the role of small molecular weight thiols

It is thought that excessive production of reactive oxygen species (ROS) can be a causal component in many diseases, some of which have an inflammatory component. This led to an oversimplification whereby ROS are seen as inflammatory and antioxidants anti-inflammatory. This paper aims at reviewing some of the literature on thiols in host defense. The review will first summarize the mechanisms by which we survive infections by pathogens. Then we will consider how the redox field evolved from the concept of oxidative stress to that of redox regulation and how it intersects the field of innate immunity. A third section will analyze how an oversimplified oxidative stress theory of disease led to a hypothesis on the role of ROS and glutathione (GSH) in immunity, respectively as pro- and anti-inflammatory mediators. Finally, we will discuss some recent research and how to think out of the box of that oversimplification and link the role of thiols in redox regulation to the mechanisms by which we survive an infection outlined in the first section

Phytochemical Composition And Oxidative Stability Of Cold-Pressed Butternut Squash (Cucurbita Moschata) And Pumpkin (Cucurbita Pepo L.) Seed Oils

Pumpkin (Cucurbita spp.), a crop native to America, represents a profitable opportunity in the Northeast. In the US, production of pumpkin has expanded greatly particularly in Illinois, Michigan, Pennsylvania, New Jersey and New York. With the appreciable volume of production intended mainly for utilization of the flesh for food processing, it is also expected that significant amounts of seeds, as part of the processing wastes, are being generated. Pumpkin seeds have been reported to contain a significant amount of highly unsaturated oil. Therefore, utilization of pumpkin seeds for oil production may add value to this crop and could help reduce food-processing waste. We studied the phytochemical composition, oxidative stability and behavior of the natural antioxidants of cold-pressed pumpkin (PSO) and butternut squash (BSO) seed oils. Experiments included quantification of carotenoid, tocopherol and phenolic content by HPLC analyses and determination of the effect of packaging light transmission properties and storage temperatures on the oxidative stability of the oils and the retention of their major antioxidant compounds. The predominant carotenoid in BSO was -carotene (21.8 mg/kg) while lutein+zeaxanthin (16.76 mg/kg) was the most abundant in PSO. [alpha]-carotene and cryptoxanthin were detected at lower concentrations but the latter was not detected in BSO. The total carotenoid content of PSO (32.4 mg/kg) was slightly lower than that of BSO (27.1 mg/kg). Significant concentrations of tocopherols ([alpha], [gamma], and [delta]) were found with [gamma]-tocopherol showing preponderance (>90%) in both oils. The total tocopherol content of BSO (563 mg/kg) was not significantly different compared to that of PSO (553 mg/kg). Two isomers ([gamma] and [delta]) of tocotrienol were also detected. The individual phenolics were tyrosol, luteolin, vanillin, vanillic acid, and trans-cinnamic acid. The oils were stable for at least 20 weeks when stored in amber bottles at temperature below 300C and we estimated a shelf-life for both oils of over 15 months based on accelerated storage test. Oxidation was most pronounced in clear bottles while green bottles provided only partial protection when exposed to 15W fluorescent light at 200C. The antioxidant compounds were better retained in amber bottles while significant reductions (p -tocopherol; lutein > -carotene. Phenolics exhibited only minor losses suggesting excellent stability of these compounds. Because of their high content of natural antioxidants and good storage stability, cold-pressed butternut squash and pumpkin seed oils demonstrate potential for valueadded uses such as production of specialty oils as natural sources of dietary antioxidants and in pharmaceutical and cosmetic applications. i

Data on chromatographic isolation of cysteine mixed-disulfide conjugates of Allium thiosulfinates and their role in cellular thiol redox modulation

This data article contains experimental data on the preparation and semi-preparative isolation of S-Alk(en)ylmercaptocysteine (CySSRs, R = allyl, “A”, 1-propenyl, “Pe” or methyl, “Me”) generated through conjugation reactions between allyl and 1-propenyl enriched thiosulfinates (TS) and cysteine. The data presented are related to the research article “S-Alk(en)ylmercaptocysteine suppresses LPS-induced pro-inflammatory responses in murine macrophages through inhibition of NF-κB pathway and modulation of thiol redox status” (Tocmo and Parkin, in press). In this data article, we included a detailed procedure for CySSR preparation, their purification through semi-preparative chromatography and their toxicity profiles in RAW 264.7 macrophages. Data included also highlight, the ability of CySSRs to modulate intracellular thiol redox status