Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.

Oxidative stress is a complex biological process characterized by the excessive production of reactive oxygen species (ROS) that act as destroyers of the REDOX balance in the body and, implicitly, inducing oxidative damage. All the metabolisms are impaired in oxidative stress and even nucleic acid balance is influenced. ROS will promote structural changes of the tissues and organs due to interaction with proteins and phospholipids. The constellation of the cardiovascular risk factors (CVRFs) will usually develop in subjects with predisposition to cardiac disorders. Oxidative stress is usually related with hypertension (HTN), diabetes mellitus (DM), obesity and cardiovascular diseases (CVDs) like coronary artery disease (CAD), cardiomyopathy or heart failure (HF), that can develop in subjects with the above-mentioned diseases. Elements describing the complex relationship between CVD and oxidative stress should be properly explored and described because prevention may be the optimal approach. Our paper aims to expose in detail the complex physiopathology of oxidative stress in CVD occurrence and novelties regarding the phenomenon. Biomarkers assessing oxidative stress or therapy targeting specific pathways represent a major progress that actually change the outcome of subjects with CVD. New antioxidants therapy specific for each CVD represents a captivating and interesting future perspective with tremendous benefits on subject's outcome.

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder, predominantly symmetric, which causes joint inflammation, cartilage degeneration and bone erosion, resulting in deformity and the loss of physical function. Although the management of RA has steadily improved, the pathophysiological mechanism is incompletely elucidated, and therapeutic options are still limited. Due to shortcomings in the efficacy or safety profiles of conventional RA therapies, therapeutic alternatives have been considered. Therefore, natural extracts containing polyphenolic compounds can become promising adjuvant agents for RA global management, due to their antioxidant, anti-inflammatory and apoptotic properties. Polyphenols can regulate intracellular signaling pathways in RA and can generate different immune responses through some key factors (i.e., MAPK, interleukins (ILs 1 and 6), tumor necrosis factor (TNF), nuclear factor light k chain promoter of activated receptor (NF-κB), and c-Jun N-terminal kinases (JNK)). The critical function of the Toll like-receptor (TLR)-dependent mitogen-activating protein kinase (MAPK) signaling pathway in mediating the pathogenic characteristics of RA has been briefly discussed. Oxidative stress can trigger a change in transcription factors, which leads to the different expression of some genes involved in the inflammatory process. This review aims to provide a comprehensive perspective on the efficacy of polyphenols in mitigating RA by inhibiting signaling pathways, suggesting future research perspectives in order to validate their use.

Reactive oxygen species (ROS) are often seen solely as harmful byproducts of oxidative metabolism, yet evidence reveals their paradoxical roles in both promoting and inhibiting cancer progression. Despite advances, precise context-dependent mechanisms by which ROS modulate oncogenic signaling, therapeutic response, and tumor microenvironment dynamics remain unclear. Specifically, the spatial and temporal aspects of ROS regulation (i.e., the distinct effects of mitochondrial versus cytosolic ROS on the PI3K/Akt and NF-κB pathways, and the differential cellular outcomes driven by acute versus chronic ROS exposure) have been underexplored. Additionally, the specific contributions of ROS-generating enzymes, like NOX isoforms and xanthine oxidase, to tumor microenvironment remodeling and immune modulation remain poorly understood. This review synthesizes current findings with a focus on these critical gaps, offering novel mechanistic insights into the dualistic nature of ROS in cancer biology. By systematically integrating data on ROS source-specific functions and redox-sensitive signaling pathways, the complex interplay between ROS concentration, localization, and persistence is elucidated, revealing how these factors dictate the paradoxical support of tumor progression or induction of cancer cell death. Particular attention is given to antioxidant mechanisms, including NRF2-mediated responses, that may undermine the efficacy of ROS-targeted therapies. Recent breakthroughs in redox biosensors (i.e., redox-sensitive fluorescent proteins, HyPer variants, and peroxiredoxin–FRET constructs) enable precise, real-time ROS imaging across subcellular compartments. Translational advances, including redox-modulating drugs and synthetic lethality strategies targeting glutathione or NADPH dependencies, further highlight actionable vulnerabilities. This refined understanding advances the field by highlighting context-specific vulnerabilities in tumor redox biology and guiding more precise therapeutic strategies. Continued research on redox-regulated signaling and its interplay with inflammation and therapy resistance is essential to unravel ROS dynamics in tumors and develop targeted, context-specific interventions harnessing their dual roles.

Increased environmental pollution, urbanization, and a wide variety of anthropogenic activities have led to the release of toxic pollutants into the environment, including heavy metals (HMs). It has been found that increasing concentrations of HMs lead to toxicity, mineral imbalances, and serious diseases, which are occurring more and more frequently. Therefore, testing has become imperative to detect these deficiencies in a timely manner. The detection of traces of HMs, especially toxic ones, in human tissues, various biological fluids, or hair is a complex, high-precision analysis that enables early diagnosis, addressing people under constant stress or exposed to a toxic environment; the test also targets people who have died in suspicious circumstances. Tissue mineral analysis (TMA) determines the concentration of toxic minerals/metals at the intracellular level and can therefore determine correlations between measured concentrations and imbalances in the body. Framing the already-published information on the topic, this review aimed to explore the toxicity of HMs to human health, the harmful effects of their accumulation, the advantages vs. the disadvantages of choosing different biological fluids/tissues/organs necessary for the quantitative measurement of HM in the human body, as well as the choice of the optimal method, correlated with the purpose of the analysis.