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The positive effect of AM3, spermidine, and hesperidin, which have antioxidant and anti-inflammatory properties, on immunity is known, but their effect on the rate of aging, known as biological age (BA), is unclear. This work aims to test if the intake of a blend of AM3 (150 mg), spermidine (0.6 mg), and hesperidin (50 mg) for 2 months could decrease BA and improve immunity, redox, and inflammatory states. For this, 41 participants (30–63 years) were randomly divided into placebo and supplement groups. The supplement group took two capsules daily with AM3, spermidine, and hesperidin for two months, while the placebo group took capsules containing only calcium phosphate and talcum powder. Before and after the treatment, peripheral blood was collected. Immune function was assessed in leukocytes, redox state in whole-blood cells, erythrocytes, and plasma, and cytokine concentration in both mononuclear cell cultures and plasma. Finally, the Immunity Clock model was applied to determine BA. The results show that the intake of this blend improves the immune functions that constitute the Immunity Clock, decreasing BA by 11 years and reducing the oxidative–inflammatory state of the participants. Therefore, this supplement can be proposed as a strategy to rejuvenate BA and achieve healthy aging.

Acne-prone skin is a common condition in adult women, and skin imperfections could affect quality of life and self-esteem. This study aimed to investigate the efficacy of a cosmetic combination regimen for face care (a cleanser gel and a serum containing niacinamide, retinol, and alpha hydroxy acids). A total of 20 women with acne-prone mixed or oily skin were enrolled in a prospective 42-day trial. Sebum content, skin radiance, skin profilometry, and evaluation of face area occupied by pores were evaluated at baseline and after 14, 28, and 42 days. In addition, a face lipidomic evaluation was performed at baseline and after 42 days. Finally, self-assessment questionnaires at each visit checkpoint were performed to evaluate efficacy and tolerability of the tested products. All the subjects but one concluded the study. Both products were very well tolerated and 84% of the subjects reported a global clinical improvement. Skin sebum content was significantly (p < 0.05) reduced at each of the evaluation time points (−9.9% at day 14, −19.4% at day 28, and −23.7% at day 42). The tested regimen significantly decreased the gloss parameter (mattifying effect) at day 14, 28, and 42, with a maximum reduction of 7.2% at the end of the study period. The pores area demonstrated a significant reduction at each of the checkpoint evaluations in comparison with baseline. Inflammatory and non-inflammatory lesions were significantly reduced by 16% at day 28 and day 42 (p < 0.01). Lipidomic analysis demonstrated that this cosmetic face care regimen induced significant and positive effects in face sebum lipids composition, characterized by a significant increase in ceramides and triacylglycerols and a decrease in fatty acids and oxidized fatty acids.

Sensitive skin has a great impact on the quality of life of subjects. In this research, we evaluated the efficacy and tolerance of a cosmetic treatment for facial skincare, consisting of a cleanser, serum and cream. A clinical-instrumental study was carried out on 30 healthy female participants with sensitive and reactive skin and slight-to-moderate wrinkles using a new cosmetic regimen based on a new technology. Skin moisturization, skin barrier function, erythema, elasticity and firmness, and wrinkle depth (skin profilometry) were evaluated at basal time (T0), and after 14, 28 and 42 days of treatment (T14, T28 and T42). All the evaluated variables showed significant improvement at T42 when compared to T0. Moisturization, erythema, firmness, and elasticity had significant improvement at T14 and the other attributes after T28 (transepidermal water loss, wrinkle depth). A high level of tolerance and satisfaction reported by subjects were achieved. This treatment regimen combining the cleanser, the daily cream, and the nightly serum, showed a statistically significant improvement in all of the parameters evaluated, demonstrating its effectiveness as an anti-aging regimen while improving the sensitive skin condition. This regimen was well tolerated by all the participants.

Since their discovery, innate lymphoid cells (ILCs) have gradually been gaining greater relevance in the field of immunology due to their multiple functions in the innate immune response. They can mainly be found in mucosal and barrier organs like skin, gut, and lungs, and have been classified into five main types (NKs, ILC1s, ILC2s, ILC3s, and Lti cells) according to their function and development. They all play major roles in functions such as tissue homeostasis, early pathogen defense, regulation of inflammation, or tissue remodeling. ILCs are mostly tissue-resident cells tightly bound to the tissue structure, a fact that requires long and complex protocols that do not always provide sufficient yield for analysis. This suggests the need for optimized approaches aimed at ensuring that enriched and viable ILC samples are obtained, in order to furnish quality results. Herein a detailed protocol is established for obtaining a single-cell suspension highly enriched in lymphoid cells from mouse gut in order to identify the different subsets of ILCs by means of flow cytometry. The cell marker panel and flow cytometry gating strategies for identification and quantification of all the different ILC populations are provided for simultaneous analysis. Moreover, the protocol described includes a procedure for studying the different cytokines produced by ILC3s involved in maintaining the integrity of the gut barrier and defending against extracellular pathogens. As a result, herein an efficient method is presented for studying mouse ILCs within the lamina propria of the small intestine and colon; this can constitute a useful tool for future investigations in the field.

Summary: Group 3 innate lymphoid cells (ILC3s) are vital for defending tissue barriers from invading pathogens. Hypoxia influences the production of intestinal ILC3-derived cytokines by activating HIF. Yet, the mechanisms governing HIF-1α in ILC3s and other innate RORγt+ cells during in vivo infections are poorly understood. In our study, transgenic mice with specific Hif-1a gene inactivation in innate RORγt+ cells (RAG1KO HIF-1α▵Rorc) exhibit more severe colitis following Citrobacter rodentium infection, primarily due to the inability to upregulate IL-22. We find that HIF-1α▵Rorc mice have impaired IL-22 production in ILC3s, while non-ILC3 innate RORγt+ cells, also capable of producing IL-22, remain unaffected. Furthermore, we show that IL-18, induced by Toll-like receptor 2, selectively triggers IL-22 in ILC3s by transcriptionally upregulating HIF-1α, revealing an oxygen-independent regulatory pathway. Our results highlight that, during late-stage C. rodentium infection, IL-18 induction in the colon promotes IL-22 through HIF-1α in ILC3s, which is crucial for protection against this pathogen.

IntroductionThe Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease.MethodsWe analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells.ResultsExposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines.ConclusionWe have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.

Cancer is a multifactorial chronic illness caused by a combination of genetic and environmental factors. A tumor is more than just a collection of cancer cells, it also contains infiltrating and resident host cells that are constantly interacting with it. Innate lymphoid cells (ILCs) have been recently found to be within the tumor and its microenvironment in close relationship with cancer cells. Although ILCs lack an antigen-specific receptor, they can respond to environmental stress signals, aiding in the fast orchestration of an early immune response. They are tissue resident cells mostly located in mucosa and first barrier organs that have been mainly studied in the defense against pathogens, lymphoid development, and tissue repair, however, current research has begun to elucidate their involvement in carcinogenesis. Nevertheless, among all ILCs, ILC3s have been found to be the most controversial in terms of tumor immunity. It has been found that they enhance anti-tumor immunity by detecting cancerous cells and helping lymphocytes infiltrate tumors. However, some recent studies have revealed that IL-23 stimulating ILC3s may promote tumor growth. In this review, we have incorporated the most recent studies on the involvement of ILC3s in cancer development to offer an overview of the role of ILC3s in cancer emphasis on their particular activity in several organs primarily in the mucosa, but also in breast, pancreas, liver, and skin, realizing that their role likely depends on the tissue microenvironment and the subtype of ILC3s.

Type 3 Innate lymphoid cells (ILC3s) have been described as tissue-resident cells and characterized throughout the body, especially in mucosal sites and classical first barrier organs such as skin, gut and lungs, among others. A significant part of the research has focused on their role in combating pathogens, mainly extracellular pathogens, with the gut as the principal organ. However, some recent discoveries in the field have unveiled their activity in other organs, combating intracellular pathogens and as part of the response to viruses. In this review we have compiled the latest studies on the role of ILC3s and the molecular mechanisms involved in defending against different microbes at the mucosal surface, most of these studies have made use of conditional transgenic mice. The present review therefore attempts to provide an overview of the function of ILC3s in infections throughout the body, focusing on their specific activity in different organs.