Amirhossein Faghih Ojaroodi

Leukemia represents a heterogeneous group of hematologic malignancies characterized by the dysregulated proliferation, differentiation, and survival of hematopoietic cells. Vitamin D (VD), a fat-soluble secosteroid hormone, is increasingly recognized not only as a regulator of calcium–phosphate metabolism but also as an important immune–metabolic modulator involved in hematopoietic homeostasis, inflammatory signaling, and cellular fate determination. Growing evidence suggests that VD deficiency may influence leukemogenesis, disease progression, treatment responsiveness, and supportive-care outcomes in patients with leukemia. Mechanistic studies indicate that the active metabolite, 1,25-dihydroxyvitamin D₃ (calcitriol), modulates leukemic cell biology by activating the vitamin D receptor (VDR) and regulating genomic and non-genomic signaling pathways, including MAPK, PI3K/AKT/mTOR, JAK/STAT, NF-κB, and β-catenin. Through these pathways, VD may affect transcriptional programs governing proliferation, differentiation, apoptosis, autophagy, immune regulation, and treatment resistance. Clinical and observational studies suggest that low 25-hydroxyvitamin D levels may be associated with adverse outcomes in selected leukemia subtypes, including poorer treatment responses, shorter overall survival and relapse-free survival, and shorter time to treatment. However, the available data remain heterogeneous, and causality has not been established. This review provides an integrated translational synthesis of VD deficiency in leukemia, linking molecular mechanisms with subtype-specific clinical evidence and supportive-care implications. Although VD supplementation should not be considered an independent anti-leukemic therapy, individualized assessment and correction of deficiency may represent a rational, low-toxicity component of supportive care. Further prospective and interventional studies are needed to define optimal supplementation strategies, identify responsive patient subgroups, and clarify the clinical relevance of VD status in leukemia.

Peripheral artery disease (PAD) is a common vascular disorder in the elderly, often accompanied by frailty syndrome, which is associated with increased inflammation, oxidative stress, and functional decline. Nutritional strategies, particularly those involving bioactive compounds like flavonoids and omega-3 fatty acids, have been suggested as potential approaches to modulate these pathological processes. This narrative review summarizes current evidence regarding the anti-inflammatory and antioxidant effects of flavonoids and omega-3 fatty acids, and their possible roles in mitigating frailty syndrome in patients with PAD. We examine mechanistic pathways including NF-κB, AMPK, PI3K/Akt/mTOR, and Nrf2, which are implicated in chronic inflammation, endothelial dysfunction, and muscle wasting. Although studies in general and aging populations suggest beneficial effects of these compounds on vascular and muscle health, specific evidence in PAD patients remains limited. Flavonoids may reduce pro-inflammatory cytokine production and enhance antioxidant responses, while omega-3 fatty acids have shown potential in modulating inflammatory signaling and supporting vascular repair. Current data provide a basis for further investigation into the dietary modulation of frailty syndrome in PAD. Understanding the impact of these nutrients may offer insights into adjunctive strategies for improving patient outcomes.

Vitamin D (VD) is a vital lipophilic secosteroid hormone known for its essential role in maintaining skeletal health and regulating calcium and phosphate metabolism. Recent evidence has begun to illuminate its significance beyond bone health, particularly in relation to thrombosis—a condition characterized by blood clot formation within the vascular system that can lead to serious cardiovascular events such as myocardial infarction and stroke. VD deficiency, defined as a plasma 25-hydroxyVD level below 25 nmol/L, affects a substantial portion of the global population, with prevalence rates ranging from 8% to 18%. This study systematically explores the relationships between VD levels and the risk of thrombosis, investigating the underlying mechanisms including VD’s anticoagulant properties, influence on inflammatory pathways, and interactions with endothelial cells. Epidemiological data suggest that low serum levels of VD correlate with an increased risk of venous thromboembolism (VTE), although the reported findings remain inconsistent. Mechanisms that potentially link VD to thrombotic risk include modulation of thrombomodulin and tissue factor expression, as well as enhancement of anti-inflammatory cytokines. Given the prevalence of VD insufficiency, particularly among populations with limited exposure to sunlight, this research highlights the urgent need for strategies to increase VD levels through dietary modifications and supplementation in order to prevent thrombotic events.