Esteban Orenes-Piñero

The tumour immune microenvironment is increasingly recognised as a critical determinant of cancer progression, prognosis, and therapeutic response, challenging the sufficiency of anatomy-based staging systems such as TNM. The Immunoscore (IS), originally validated in colorectal cancer, provides a standardised, spatially resolved assessment of CD3 ⁺ and CD8 ⁺ T cells within the tumour core (TC) and invasive margin (IM). Expanding upon this framework, adapted and modified IS models, as well as computational and imaging-based surrogates, have been investigated across multiple solid malignancies, including non-small-cell lung cancer, hepatocellular carcinoma, head and neck cancers, gastric cancer, melanoma, and bladder cancer. This review synthesises the current evidence, emphasising both the translational potential and methodological heterogeneity of IS-based approaches. High IS or adapted scores generally correlate with improved survival and may refine risk stratification, complementing conventional TNM staging. However, inter-study variability limits comparability and reproducibility. Retrospective designs, single-centre cohorts, limited external validation, and potential overfitting in computational models further constrain the strength of evidence. Biological context dependency, immune-exclusion phenotypes, and the dynamic evolution of the tumour immune landscape complicate interpretation, underscoring that high immune cell density does not universally equate to effective antitumour immunity. Overall, the IS and related immune-contexture classifiers constitute a biologically grounded framework that bridges tumour immunology and clinical oncology. While promising, widespread clinical implementation requires methodological harmonisation, prospective validation, and integration with genomic, systemic, and imaging biomarkers. By highlighting both achievements and current limitations, this review provides a balanced perspective on the potential and challenges of translating immune contexture-based metrics into precision oncology.

Acute lymphoblastic leukemia (ALL) remains the most frequent pediatric malignancy, accounting for approximately 34% of all pediatric cancers, with remarkable improvements in survival (approximately 85%) due to advances in chemotherapy, radiotherapy, and supportive care. However, as survival rates have increased, new challenges have emerged—particularly the growing prevalence of obesity and metabolic syndrome among survivors. This review compiles evidence from the past decade on the relationship between leukemia treatment, obesity, and metabolic risk. The findings indicate that cranial radiotherapy, corticosteroid use, and younger age at diagnosis are key risk factors for excessive weight gain and long-term metabolic disturbances. Genetic factors such as FTO, MC4R, and LEPR polymorphisms may further influence susceptibility to obesity. Nutritional analyses highlight poor diet quality, insufficient micronutrient intake, and high-fat, energy-dense dietary patterns in survivors. Beyond endocrine dysfunction, obesity and metabolic syndrome are associated with elevated cardiovascular morbidity and reduced quality of life. Personalized medicine approaches—integrating genomics, metabolomics, and lifestyle data—hold promise for targeted prevention and intervention strategies. Early detection, continuous metabolic monitoring, and health education remain essential components in the long-term management of childhood leukemia survivors. In this review, we analyzed the dietary patterns of children and long-term leukemia survivors explaining why higher rates of obesity and comorbidities appear during or after treatments, and discussed interventions to prevent these conditions.

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.

Acute coronary syndrome (ACS) is a leading cause of global mortality, largely due to atherosclerosis influenced by lifestyle factors like diet. Gut microbiota impacts lipid metabolism, inflammation, and endothelial function, all vital in atherosclerosis. Dysbiosis increases intestinal permeability, causing inflammation and plaque instability, elevating cardiac event risk. This study investigates the impact of dietary improvements on gut microbiota and metabolite release in recent ACS patients versus healthy individuals. A cohort of 29 recent ACS patients receiving lipid‐lowering therapy and dietary advice was analyzed alongside 56 healthy controls. Dietary habits, serum, and stool samples were collected at admission and after 3 months. Metagenomic analysis of stool and metabolomic analysis of serum were conducted. The results showed bacterial dysbiosis in ACS patients, characterized by a reduction in beneficial genera and an increase in potentially pro‐inflammatory bacteria. After 3 months of dietary improvements, three metabolites with anti‐inflammatory properties were significantly upregulated. The findings highlight the association between gut microbiota dysbiosis, fatty diets, and inflammation in ACS patients. The observed increase in anti‐inflammatory metabolites following dietary changes underscore the following dietary interventions in modulating gut microbiota and improving cardiovascular and metabolic health.

The gut microbiota can affect both the enteric and the central nervous system, influencing individuals and their brain regulation. In this work, different pieces of scientific evidence are discussed, showing the relationship between changes in the microbiota and neurocognitive deterioration, focussing on Parkinson’s disease (PD). Other factors that may cause or contribute to PD aetiology are the interactions between environmental factors and genetic susceptibility. According to the existing literature, there are several methods for the identification of neurocognitive impairment in different neurological diseases. However, such methods do not allow early identification, and therefore, the possibility of using other types of more effective diagnostic biomarkers in PD has also been investigated. Since this disease is characterised by specific microRNA (miRNA) expression, and the gut microbiota is an important factor in both PD and miRNA expression, the aim of this review is thoroughly analysing the role of microbiota and microRNAs in PD development. In addition, the relationship between these two factors and potential treatments will be also discussed.

Importance: Infertility affects around 180 million people in the world and can be influenced by a number of nutritional factors. Objective: The idea of a pretreatment optimization including beneficial weight loss, adequate physical activity, and good lifestyle habits could enhance fertility for many couples who want to conceive a baby. Results: There are different aspects related to nutrition, such as obesity (affecting 23%–30% of reproductive-aged women), dietary patterns (type of diet, good or bad habits, and physical activity), nutrients (vitamins or minerals), hormones (adipokines, among others), and endocrine-disrupting chemicals (phytoestrogens and bisphenol A, among others) that have a clear impact on women’s fertility. Evidence Acquisition: Findings have shown that a Mediterranean or balanced diet with an adequate weight loss in case of obesity and an appropriate serum concentration of different nutrients with low endocrine-disrupting exposure could improve female fertility. In addition, the context is quite important, as there are many differences between overweight and low-weight women, and both can encounter difficulties conceiving. Conclusions and Relevance: The aim of this review is to elucidate the impact of obesity and hormones in women’s fertility. In addition, how dietary patterns could help people to increase probability of conception and birth using less fertility treatments cycles will be also analyzed. Moreover, the role of endocrine-disrupting chemicals, pollutants, and contaminants will be discussed. Target Audience: Obstetricians and gynecologists, family physicians. Learning objectives: After completing this activity, the learner will be better able to discuss how obesity and hormones impact fertility; explain the role of dietary patterns regarding conception and birth; and describe the effect of endocrine-disrupting chemicals, pollutants, and contaminants.

Scope: Inflammatory bowel disease (IBD) is one of the most common chronic and debilitating functional bowel disorders affecting around 11% of the population across the world. IBD is associated with 3.6 million physician visits per year, being the most common reason visiting a gastroenterologist and the second most common reason to be absent from work, sharply increasing the health care costs.Methods and Results: Several treatments seem to be effective in IBD symptoms relief, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary patterns. Probiotics (living microorganisms that can be supplemented) can protect against pathogenic bacteria due to their antimicrobial qualities. Prebiotics (nondigestible food ingredients) promote the growth of beneficial microbial strains in the gut, giving a health benefit to the host. FMT is supposed to directly change the recipient's microbial composition when a transfer of gastrointestinal microbiota from a healthy donor is carried out. And finally, dietary patterns are in the spotlight, due to the presence of certain nutrients in the gastrointestinal tract affecting gastrointestinal motility, sensitivity, barrier function, and gut microbiota.Conclusion: It is particularly important to know what treatment options are available and which are the most efficient in relieving IBD symptoms and improving IBD patient's quality of life.

Scope: High blood pressure (BP) is the main preventable risk factor for cardiovascular diseases (CVDs). Much research is aimed at finding natural alternatives to control or prevent hypertension (HT), since some hypertensive patients do not respond to current pharmacological treatments or show undesirable side effects.Methods and results: Forty relevant articles have been selected from various scientific literature databases. The results reveal that angiotensin‐converting enzyme (ACE) inhibition is the most reported mechanism of action of antihypertensive peptides. The active peptides have a great variety of origins. Biopeptides with a molecular weight of <3 kDa, short chain <20 amino acids, and a hydrophobic amino acid sequence at the C‐ and N‐terminus exhibit higher antihypertensive activity. They also show good stability to enzymatic hydrolysis and gastrointestinal digestion, and no toxicity. To determine antihypertensive effectiveness, in vitro and in vivo animal studies are the most frequent developed, with few in silico studies and only one human clinical trial.Conclusion: There is interesting potential for antihypertensive peptides as promising natural candidates for the development of functional foods, nutraceuticals and drugs for preventive or therapeutic treatment of hypertension. The aim of this review is to study the role of food‐derived bioactive peptides in HT.

The tumor immune microenvironment of thyroid cancer is the heterogeneous histological space in which tumor cells coexist with host cells. Published data from this review were identified by search and selection database of Pubmed, Elsevier, and Science Direct. Searching was made in two steps using different keywords. In thyroid pathology, the inflammatory response is very important, and might have a key role finding new diagnostic and therapeutic methods, particularly in thyroid cancer. Different immune cells may be more or less present in different types of thyroid cancer and may even have different functions, hence the importance of knowing their presence in different thyroid tumor pathologies. Cancer‐related inflammation could be a useful target for new diagnostic and therapeutic strategies by analyzing peritumoral and intratumoral immune cells in different types of thyroid tumors. Moreover, novel strategies for thyroid cancer treatments, such as monoclonal antibodies targeting checkpoint inhibitors, are emerging as promising alternatives.