Diabetic foot ulcers (DFUs) are among the most common and debilitating complications of diabetes mellitus (DM), affecting approximately 15–25% of patients and contributing to over 85% of non-traumatic amputations. DFUs impose a substantial clinical and economic burden due to high recurrence rates, prolonged wound care, and frequent hospitalizations, accounting for billions in healthcare costs worldwide. The multifactorial pathophysiology of DFUs involves peripheral neuropathy, peripheral arterial disease, chronic inflammation, and impaired tissue regeneration. Recent studies underscore the importance of immune dysregulation—specifically macrophage polarization imbalance, regulatory T cell dysfunction, and neutrophil impairment—as central mechanisms in wound chronicity. These immune disruptions sustain a pro-inflammatory environment dominated by cytokines, such as TNF-α, IL-1β, and IL-6, which impair angiogenesis and delay repair. This review provides an updated synthesis of DFU pathogenesis, emphasizing immune dysfunction and its therapeutic implications. We examine emerging strategies in immunomodulation, regenerative medicine, and AI-based wound technologies, including SGLT2 inhibitors, biologics, stem cell therapies, and smart dressing systems. These approaches hold promise for accelerating healing, reducing amputation risk, and personalizing future DFU care.

Type 2 diabetes mellitus (T2DM) is significantly associated with oxidative stress, resulting from the imbalance between reactive oxygen species (ROS) production and antioxidant defenses. This imbalance contributes to insulin resistance, β-cell dysfunction, and complications in organs like the vasculature and nervous system. Glutathione (GSH), a major antioxidant, is crucial for neutralizing ROS, but GSH levels are notably low in T2DM, exacerbating oxidative stress and inflammation. Elevated interleukin-6 (IL-6) levels further intensify inflammation and oxidative stress, disrupting insulin signaling and worsening complications such as nephropathy, retinopathy, and neuropathy. While lifestyle modifications and antioxidant supplementation are current approaches for managing oxidative stress, their effectiveness in preventing complications remains under study. Recent investigations suggest that GSH and Vitamin D3 supplementation may offer dual-action benefits, as Vitamin D3 not only has anti-inflammatory properties but also promotes GSH synthesis. This dual action helps mitigate both oxidative stress and inflammation, addressing key pathological features of T2DM. This review highlights the complex interactions between oxidative stress, GSH insufficiency, and IL-6, and emphasizes the potential of targeted therapies to improve the management and outcomes of T2DM.

This review explores ferroptosis, a form of regulated cell death reliant on iron-induced phospholipid peroxidation, in diverse physiological and pathological contexts, including neurodegenerative disorders, and ischemia-reperfusion. In the realm of cardiovascular diseases, it significantly contributes to cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. Ferroptosis involves intricate interactions within cellular iron metabolism, lipid peroxidation, and the balance between polyunsaturated and monounsaturated fatty acids. Molecularly, factors like p53 and NRF2 impact cellular susceptibility to ferroptosis under oxidative stress. Understanding ferroptosis is vital in cardiomyopathies, where cardiac myocytes heavily depend on aerobic respiration, with iron playing a pivotal role. Dysregulation of the antioxidant enzyme GPX4 is linked to cardiomyopathies, emphasizing its significance. Ferroptosis’s role in myocardial ischemia-reperfusion injury, exacerbated in diabetes, underscores its relevance in cardiovascular conditions. This review explores the connection between ferroptosis, the NRF2 pathway, and atherosclerosis, emphasizing their roles in protecting cells from oxidative stress and maintaining iron balance. It discusses the use of iron chelating agents in managing iron overload conditions, with associated benefits and challenges. Finally, it highlights the importance of exploring therapeutic strategies that enhance the glutathione (GSH) system and the potential of natural compounds like quercetin, terpenoids, and phenolic acids in reducing oxidative stress.

Systemic lupus erythematosus (SLE) poses a diagnostic challenge due to its heterogeneity. This study examines the cardiac complications of SLE comprehensively, covering pericarditis, myocarditis, pleural effusion, valvular disease, atherosclerosis, and cardiac arrhythmias. Nearly one-third of SLE-related deaths are attributed to cardiovascular diseases, necessitating a deeper understanding of cardiac pathophysiology. The impact of SLE on the cardiovascular system manifests in various ways, including recurrent and resistant pericarditis, severe myocarditis, and pleural effusion. Valvular diseases, atherosclerosis, and cardiac arrhythmias are prevalent, with immune complex deposition playing a role in atherosclerosis. Diagnostic criteria involve clinical features, laboratory findings, and autoantibodies, emphasizing the need for early diagnosis and a multidisciplinary diagnostic approach. The review explores pharmacological and non-pharmacological modalities for managing cardiac manifestations in SLE. Recommendations include NSAIDs, colchicine, and proton pump inhibitors for acute pericarditis, while selective immunosuppressive therapy is emerging for myocarditis. Valvular diseases require individualized treatment approaches, and careful corticosteroid management is crucial to avoid increased cardiovascular events. Anti-malarial therapy, particularly hydroxychloroquine, shows promise in mitigating cardiovascular risk factors. Non-pharmacological modifications, such as diet, exercise, and smoke cessation, significantly contribute to cardiovascular health in SLE patients. Adjuvant therapies involving glutathione and glutathione peroxidase focus on redox balance, offering potential interventions. This integrated approach combines diagnostic insights with diverse treatment modalities, providing a holistic strategy for managing cardiac complications in SLE. Ongoing research is essential to refine these strategies and optimize individualized treatment plans for improved patient outcomes.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) remains a global health crisis, with over 10 million people affected annually. Despite advancements in treatment, M.tb has developed mechanisms to evade host immune responses, complicating efforts to eradicate the disease. Two emerging cell death pathways, ferroptosis and cuproptosis, have been linked to TB pathogenesis. Ferroptosis, an iron-dependent form of cell death, is driven by lipid peroxidation and reactive oxygen species (ROS) accumulation. This process can limit M.tb replication by depleting intracellular iron and inducing macrophage necrosis. However, excessive ferroptosis may lead to tissue damage and aid bacterial dissemination. Cuproptosis, triggered by copper accumulation, disrupts mitochondrial metabolism, leading to protein aggregation and cell death. M.tb exploits both iron and copper metabolism to survive within macrophages, manipulating these processes to resist oxidative stress and immune responses. This review examines the roles of ferroptosis and cuproptosis in TB, discussing how M.tb manipulates these pathways for survival. While therapeutic strategies targeting these processes, such as ferroptosis inducers (Erastin, RSL3) and inhibitors (Ferrostatin-1) and copper ionophores (Disulfiram, Elesclomol) and chelators, show promise, the limited understanding of these pathways and potential off-target effects remains a significant challenge. Further exploration of these pathways may provide insights into the development of targeted therapies aimed at controlling M.tb infection while minimizing host tissue damage. By elucidating the complex interactions between ferroptosis, cuproptosis, and TB, future therapies could better address bacterial resistance and improve clinical outcomes.

Inguinal hernia represents a multifactorial condition driven by extracellular matrix (ECM) dysregulation, collagen imbalance, and oxidative stress. Across studies, a consistent reduction in the collagen I:III ratio, coupled with altered expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), underpins weakened fascia and hernia susceptibility. Aging further impairs ECM remodeling through fibroblast senescence, cross-linking deficits, and elastic fiber attrition, while oxidative stress and inflammation amplify tissue degradation and impair repair mechanisms. Evidence from clinical and experimental studies underscores the interplay between surgical technique, mesh choice, redox balance, and recurrence risk. Understanding the combined impact of aging and oxidative stress provides a mechanistic framework for targeted therapeutic and surgical strategies aimed at preventing hernia development and recurrence.