Ischemic stroke is one of the leading causes of morbidity and mortality worldwide, with carotid atherosclerosis being its key etiological factor. MicroRNA-21 (miR-21) regulates intracellular signal pathways responsible for vascular changes and ischemic brain injury, and is recognized as a potential diagnostic and prognostic biomarker. It modifies the activity of macrophages (MΦ) and vascular smooth muscle cells, causing inflammation and affecting the stability of atherosclerotic plaques. A deficiency of miR-21 in macrophages stimulates the inflammatory response and plaque growth. It promotes both the synthesis of extracellular matrix, stabilizing the plaque, and the degradation of the fibrin cap, which leads to plaque instability. The effect of miR-21 on endothelial cells differs: it stimulates both NO· synthesis and inflammation. During ischemic stroke, miR-21 demonstrates neuroprotective effects by modulating post-ischemic inflammation and protecting the integrity of the blood–brain barrier. Therapy targeting miR-21 shows potential in experimental models, but it requires cell-specific delivery and precise timing. Further research efforts should focus on the effects of miR-21 on different cell types, as well as the development of new technologies for diagnostic and therapeutic applications.

Ischemic heart disease (IHD) remains a leading cause of global morbidity and mortality despite advances in prevention, diagnosis, and therapy. Traditional clinical risk scores and biomarkers often fail to fully capture the complex molecular processes underlying atherosclerosis, myocardial infarction, and ischemic cardiomyopathy, leaving substantial residual risk. MicroRNAs have emerged as promising regulators and biomarkers of cardiovascular disease, among which microRNA-21 (miR-21) has attracted particular attention. MiR-21 is deeply involved in key pathophysiological mechanisms of IHD, including endothelial dysfunction, vascular inflammation, vascular smooth muscle cell proliferation, plaque development and vulnerability, cardiomyocyte survival, and myocardial fibrosis. Accumulating clinical evidence suggests that circulating miR-21 holds diagnostic value across the ischemic continuum, from stable coronary artery disease to acute coronary syndromes, myocardial infarction, and ischemic heart failure. Moreover, miR-21 demonstrates prognostic relevance, correlating with plaque instability, adverse remodeling, heart failure progression, and long-term cardiovascular outcomes. Preclinical studies further indicate that miR-21 represents a double-edged therapeutic target, offering cardio protection in acute ischemic injury while contributing to fibrosis and maladaptive remodeling if dysregulated. This narrative review summarizes current evidence on the diagnostic, prognostic, and therapeutic utility of miR-21 in IHD, highlighting its clinical promise as well as key limitations and future translational challenges.

Chronic pain, sleep disturbances, and mental health disorders such as anxiety and depression disorders frequently co-occur, forming a self-reinforcing cycle that impairs daily functioning and quality of life. Chronic pain is driven by peripheral and central sensitization, the latter sustained by reciprocal microglial–astrocytic crosstalk and maladaptive neuroplasticity. Poor sleep amplifies pain through inflammation and circadian disruption. Imbalances in serotonin, dopamine, and norepinephrine, together with limbic alterations and HPA axis dysregulation, contribute to comorbid anxiety and depression. Elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α), NF-κB-driven neuroinflammation, and mitochondrial oxidative stress serve as key molecular links. Building on previous evidence, this review presents an updated triadic, mechanism-based framework describing the reciprocal reinforcement among chronic pain, sleep disturbances, and anxiety and depressive disorders. Consequently, therapeutic strategies targeting inflammatory cytokines, microglial and astrocytic activation, neurotransmitter imbalance, and psychological dysfunction may help address these shared neuroimmune and neuroplastic mechanisms underlying these interconnected disorders.