Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease characterized by inflammation, demyelination and axonal degeneration. There are different types of MS: Relapsing-Remitting, Primary-Progressive, Progressive-Relapsing and Secondary-Progressive disease. The prevalence of this pathology is about two million people worldwide, affecting at the age of 20–40 years, with predominance in females. The idea of remitting symptoms by modification of gut microbiota has been hypothesize through different studies, and it could have a positive impact in quality of life on these patients. Gut microbiota affects the development and regulation of the immune system, so it could be considered as a new environmental risk factor. Moreover, as a potential risk factor, it could be positively changed by diet, suggesting new therapeutic avenues and creating a protective environment based in microbiota modifications and/or nutritional interventions. Nowadays, there is strong evidence showing a relationship between the immune system and the inflammatory state. Thus, it is of paramount importance to elucidate how gut microbiota could impact on the inflammatory state of MS to improve disease´s symptoms. The aim of this review is to comprehensively analyze the relationship between gut microbiota and the inflammatory state on MS, including a nutritional therapy to calm down the symptoms.

Plants produce a diverse array of secondary metabolites, with hydroxytyrosol (HT) and its derivatives distinguished by their antioxidant and chemopreventive properties. Upon dietary consumption, native HT undergoes extensive biotransformation, initially facilitated by the gut microbiota. Increasing evidence suggests that several of these downstream products, rather than the parent molecule, are responsible for the most significant biological effects in mammalian cells. The identification of novel metabolites may reveal unknown metabolic pathways, more particularly in distinct pathological contexts such as cancer. The in vitro simulated gastrointestinal digestion (INFOGEST method) of HT, followed by bioavailability in the tumoral metabolically active intestinal Caco-2 cells (50 µM HT for 2, 4, and 6 h), was performed. Subsequently, an untargeted metabolomic analysis on the supernatant revealed novel HT-derived entities compared with water. Among these, ethoxy phenylacetic acid sulfates (4, 5), ethyl hydroxyphenylacetate acid sulfate (6) and ethoxy hydroxyphenylacetic acid or ethyl hydroxyphenylacetate glucuronide were described for the first time in a study and confirmed by MS/MS fragmentation. These accumulated ethylated forms were undetectable in non-tumoral plasma samples from HT-supplemented humans (60 mg day⁻¹ HT for 28 days) and mice (50 mg kg⁻¹ day⁻¹ HT for 2 months), suggesting a tumour-specific or, at the very least, tumour-favoured biotransformation pathway. These findings not only expand the diversity of HT metabolites but also propose ethoxy-phenylacetic acid and its sulfate conjugate as potential biomarkers for cancer detection.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide, highlighting the urgent need for improved preclinical models to evaluate potential therapies. Animal models are essential for elucidating tumor biology and assessing novel therapeutic interventions. Mouse models offer key advantages over existing models, including genetic manipulability, rapid reproduction, cost-effectiveness, and the availability of immunocompetent and immunodeficient strains, enabling precise modeling of human cancers. This protocol focuses on the subcutaneous induction of the bioluminescent colorectal cancer cell line HCT-116 in an immunodeficient murine model, followed by non-invasive bioluminescence imaging using the IVIS system and caliper to monitor tumor progression and growth. Using luminescent cells provides a real-time, quantifiable approach for tracking tumor development and response to therapeutic interventions, reducing the need for invasive procedures. A cohort of mice (n = 12) is required for tumor cell implantation, and luminescence intensity is measured to establish a standardized model for therapeutic testing. Tumor volume is typically calculated using only length and width measurements or width. The current methodology ensures consistent tumor establishment while minimizing° variability, ultimately enhancing the reliability of preclinical assessment. The findings of this study will contribute to refining tumor models for drug testing and improving the translational potential of preclinical research in clinical applications. By employing advanced imaging techniques and a reproducible experimental design, this study aims to improve the accuracy and efficiency of in vivo drug evaluation for colorectal cancer treatment.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide, highlighting the urgent need for improved preclinical models to evaluate potential therapies. Animal models are essential for elucidating tumor biology and assessing novel therapeutic interventions. Mouse models offer key advantages over existing models, including genetic manipulability, rapid reproduction, cost-effectiveness, and the availability of immunocompetent and immunodeficient strains, enabling precise modeling of human cancers. This protocol focuses on the subcutaneous induction of the bioluminescent colorectal cancer cell line HCT-116 in an immunodeficient murine model, followed by non-invasive bioluminescence imaging using the IVIS system and caliper to monitor tumor progression and growth. Using luminescent cells provides a real-time, quantifiable approach for tracking tumor development and response to therapeutic interventions, reducing the need for invasive procedures. A cohort of mice (n = 12) is required for tumor cell implantation, and luminescence intensity is measured to establish a standardized model for therapeutic testing. Tumor volume is typically calculated using only length and width measurements or width. The current methodology ensures consistent tumor establishment while minimizing° variability, ultimately enhancing the reliability of preclinical assessment. The findings of this study will contribute to refining tumor models for drug testing and improving the translational potential of preclinical research in clinical applications. By employing advanced imaging techniques and a reproducible experimental design, this study aims to improve the accuracy and efficiency of in vivo drug evaluation for colorectal cancer treatment.

Cardiovascular diseases are a leading cause of mortality, driving the search for alternative preventive strategies. This study investigates the antioxidant effects, among others, of a mixture of four bioactive peptides (BPs) derived from dry-cured pork ham on endothelial cells from healthy (C-HUVECs) and gestational diabetes (GD-HUVECs) pregnancies, as well as human plasma, using an integrative omics approach. Human umbilical vein endothelial cells (HUVECs) were treated with 300 μM purified BP, followed by transcriptomic and proteomic analyses. The results revealed significant alterations in mitochondrial gene expression and downregulation of genes associated with inflammation and oxidative stress in healthy HUVECs. Furthermore, BP treatment modulated key signalling pathways, including Ras and MAPK, leading to changes in the phosphorylation of ERK, AKT, and NF-κB, suggesting potential cardioprotective effects. The effects of BP were compared to those of the antioxidant hydroxytyrosol, highlighting their relative efficacy in vascular protection. The proteomic analysis of human plasma demonstrated BP-induced modulation of lipid metabolism, inflammation, and oxidative stress with notable changes in proteins such as APOA1 and MMP-8. These natural compounds demonstrate significant preventive potential in vascular health, highlighting their promise as effective tools for reducing cardiovascular risk before the progression of the pathology. These findings emphasize the importance of integrative omics in understanding the mechanisms behind BP’s effects and suggest promising applications for nutraceuticals aimed at cardiovascular protection.