Cancer stem cells (CSCs) are a rare cancer cell population, responsible for the facilitation, progression, and resistance of tumors to therapeutic interventions. This subset of cancer cells with stemness and tumorigenic properties is organized in niches within the tumor microenvironment (TME) and presents altered regulation in a variety of metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS), as well as lipid, amino acid, and iron metabolism. CSCs exhibit similarities as well as differences when comparedto normal stem cells, but also possess the ability of metabolic plasticity. In this review, we summarize the metabolic characteristics of normal, non-cancerous stem cells and CSCs. We also highlight the significance and implications of interventions targeting CSC metabolism to potentially achieve more robust clinical responses in the future.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that often progresses to severe disability. Previous studies have highlighted the role of T cells in disease pathophysiology; however, the success of B-cell-targeted therapies has led to an increased interest in how B cells contribute to disease immunopathology. In this review, we summarize evidence of B-cell involvement in MS disease mechanisms, starting with pathology and moving on to review aspects of B cell immunobiology potentially relevant to MS. We describe current theories of critical B cell contributions to the inflammatory CNS milieu in MS, namely (i) production of autoantibodies, (ii) antigen presentation, (iii) production of proinflammatory cytokines (bystander activation), and (iv) EBV involvement. In the second part of the review, we summarize medications that have targeted B cells in patients with MS and their current position in the therapeutic armamentarium based on clinical trials and real-world data. Covered therapeutic strategies include the targeting of surface molecules such as CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) and CD19 (inebilizumab), and molecules necessary for B-cell activation such as B cell activating factor (BAFF) (belimumab) and Bruton’s Tyrosine Kinase (BTK) (evobrutinib). We finally discuss the use of B-cell-targeted therapeutics in pregnancy.

Tumor mutational burden (TMB) is considered a prototypic feature of tumor foreignness and has been established as a tumor-agnostic FDA-approved biomarker at a threshold of 10 mut/Mb for immune checkpoint inhibitors (ICI). Despite its clinical utility as a companion diagnostic for ICI across cancers, a high TMB does not consistently predict response due to technical and biological limitations. Tumor heterogeneity and purity, blood versus tissue sampling, variation in next-generation sequencing, and algorithmic evaluation attenuate the predictive value of TMB. In addition to technical standardization and moving beyond TMB as a numeric or binarized value, it is of paramount importance to consider the underlying biology and the differential contribution of mutation subsets to tumor foreignness and immunogenicity. The importance of consideration of mutations within the overall TMB that are unlikely to be immunoedited together with the density of immunogenic “quality” mutation-associated neoantigens introduces the concept of biological calibration of TMB that may enhance its clinical utility. Mutagenic processes such as microsatellite instability and ultra-mutation and cancer lineage–dependent co-mutation patterns also represent biological modifiers that enable the interpretation of the overall TMB in different contexts. In this perspective, we dissect TMB on a biological and technical level, followed by a critical assessment of the predictive role of TMB in capturing ICI response in the setting of clinical trials across human cancers. The standardization of technical methodologies, together with the interpretation of TMB on the basis of the tumor genomic landscape, represents key steps toward maximizing the predictive value of TMB for cancer immunotherapy.

Despite the rich armamentarium of available drugs against different forms of cardiovascular disease (CVD), major challenges persist in their safe and effective use. These include high rates of adverse drug reactions, increased heterogeneity in patient responses, suboptimal drug efficacy, and in some cases limited compliance. Dietary elements (including food, beverages, and supplements) can modulate drug absorption, distribution, metabolism, excretion, and action, with significant implications for drug efficacy and safety. Genetic variation can further modulate the response to diet, to a drug, and to the interaction of the two. These interactions represent a largely unexplored territory that holds considerable promise in the field of personalized medicine in CVD. Herein, we highlight examples of clinically relevant drug–nutrient–genome interactions, map the challenges faced to date, and discuss their future perspectives in personalized cardiovascular healthcare in light of the rapid technological advances.

According to the latest epidemiological data, breast cancer has recently been the most frequently diagnosed malignancy. To date, a body of evidence has established the involvement of multiple - and frequently interrelated - genetic and environmental factors in the pathogenesis of the disease. Emerging research on cancer prevention has highlighted the deterrence potential of interventions targeting environmental risk factors, particularly diet. In this aspect, the current review reveals the latest scientific results regarding epigallocatechin-3-gallate (EGCG) - a catechin most commonly found in green tea, as a potential chemopreventive dietary agent against breast cancer. in vitro studies on EGCG have demonstrated its effect on cell cycle progression and its potential to suppress several intracellular signaling pathways involved in breast cancer pathogenesis. In addition, EGCG possesses specific apoptosis-inducing characteristics that seem to enhance its role as a regulator of cell survival. Preclinical data seem to support using EGCG as an effective adjunct to EGFR-targeting treatments. The authors’ appraisal of the literature suggests that although preclinical evidence has documented the anticarcinogenic features of EGCG, limited large-scale epidemiological studies are investigating the consumption of EGCG - containing nutrients in the prevention and management of breast cancer risk. This literature review aims to liaise between preclinical and epidemiological research, surveying the existing evidence and unraveling relevant knowledge gaps.

Background/objectives: The association between adverse childhood experiences (ACEs) and asthma severity among United States (US) adults with asthma has not been well documented. In addition, whether gender differences exist in this association has been underexplored. We aimed to examine the prevalence of asthma severity in the US adult population with asthma and investigate the association between ACEs and asthma severity by using data from non-institutionalized US adults with asthma. Methods: This cross-sectional study used data from the Adult 2019 and 2020 Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Survey (ACBS), a survey of US adults aged 18 years or older in 31 US states and Puerto Rico. A total of 22934 adults with asthma participated in 2019 and 2020 ACBS. The 11 BRFSS ACE variables encompassing abuse and household dysfunction were used as ACE measures. ACE measures were summed up as cumulative ACE scores (continuous) and categorized (zero, one ACE, two ACEs, ≥ three ACEs). Asthma severity was categorized as intermittent or persistent. Weighted logistic regression models were used to assess associations of the cumulative ACE score, categorical ACE measures, and the 11 individual ACE responses with asthma severity controlling confounders. Gender differences were explored by stratifying by gender. Results: The prevalence of persistent asthma among US adults with asthma was 45.3%. The mean cumulative ACE score in adults with intermittent vs. persistent asthma was (2.43 vs. 2.70, p-value < 0.05). About 22% of adults with asthma had no ACEs, 19% had one ACE, 14% had two ACEs, and 45% had three or more ACEs. A one-unit increase in ACEs score was associated with a 5.4% increase in the odds of persistent asthma (adjusted odds ratio, aOR = 1.054 (95% confidence interval, CI = 1.01–1.10). Experiencing ≥ three ACEs compared to no ACEs was associated with 31% increased odds of persistent asthma (aOR = 1.31, 95% CI = 1.01–1.70). Individual ACE items significantly associated with persistent asthma include parent/adult ever touched you sexually (aOR = 1.33, 95% CI = 1.03–1.74), adult tried to make you touch them (aOR = 1.34, 95% CI = 1.01–1.79), any adult forced you to have sex (aOR = 1.44, 95% CI = 1.04–1.20), parental separation/divorce (aOR = 1.31, 95% CI = 1.05–1.63), and household alcohol abuse (aOR = 1.24, 95% CI = 1.01–1.53). In women, experiencing one ACE and ≥ three ACEs (compared to no ACEs) was associated with 51% and 60% increased odds of persistent asthma, respectively (aOR = 1.51, 95% CI = 1.02–2.23; aOR = 1.60, 95% CI = 1.12–2.27). No significant association was observed between ACEs and asthma severity in men; however, experiencing household physical violence (compared to no household physical violence) was associated with persistent asthma in men (aOR = 1.69, 95% CI = 1.18–2.42). Conclusions: In this cross-sectional study of US adults with asthma, exposure to ACEs was associated with higher odds of asthma overall and in women. These findings highlight the importance of preventive strategies and early interventions to reduce ACEs, potentially mitigating asthma’s severity in adulthood.