Krzysztof Majcherczyk

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency, accumulation of globotriaosylceramide (Gb3), and progressive multiorgan involvement. Increasing evidence indicates that oxidative stress plays a central role in disease pathogenesis. This review aims to synthesize current knowledge on the molecular mechanisms underlying oxidative stress, the relevance of oxidative damage biomarkers, and potential therapeutic implications. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using terms related to Fabry disease, Gb3 metabolism, mitochondrial and endothelial dysfunction, inflammatory signaling, and oxidative stress markers. Clinical, experimental, and translational studies were included. Available data demonstrate that Gb3 accumulation disrupts mitochondrial function and activates NADPH oxidase, NF-κB, and MAPK signaling pathways, resulting in excessive production of reactive oxygen species. These processes contribute to cellular injury, particularly within the cardiovascular, renal, and nervous systems. Biomarkers such as malondialdehyde, 8-hydroxy-2′-deoxyguanosine, glutathione redox status, and antioxidant enzyme activities appear useful for assessing oxidative burden and monitoring therapeutic responses. Overall, current evidence underscores the pivotal role of oxidative stress in the progression of Fabry disease and highlights the need for further research into targeted antioxidant and disease-modifying therapeutic strategies.

Ovarian tumors constitute a complex and heterogeneous group of neoplasms, encompassing both benign and highly malignant lesions. Accurate diagnosis and classification of ovarian tumor types are crucial for the personalization of therapeutic strategies and have a significant impact on patient prognosis. This review presents the current state of knowledge regarding both classical and novel biomarkers, with particular emphasis on their diagnostic, predictive, and prognostic value. Traditional markers, such as CA-125 and human epididymis protein 4 (HE4), remain central to clinical diagnostics; however, their limitations highlight the need for more sensitive and specific approaches. Emerging biomarkers, including microRNAs (miRNA), circulating tumor DNA (ctDNA), and advanced panels integrating transcriptomic, proteomic, and genomic data, offer the potential for earlier detection, improved disease monitoring, and assessment of treatment response. Despite these advances, major challenges persist, particularly those associated with the heterogeneity of ovarian tumors, the high costs of testing, lack of standardization, and unequal access to diagnostic methods.

Heart failure (HF) and other cardiac pathologies represent leading causes of hospitalization and mortality worldwide, underscoring the urgent need for effective regenerative therapies. In recent years, considerable research has focused on developing cell-based therapeutic strategies, with stem cells receiving particular attention. Approaches that harness cellular signaling pathways have also been investigated. Experimental studies conducted in both animal models and human subjects have demonstrated that cell-based therapies hold remarkable potential, showing efficacy through improvements in cardiac function, patient quality of life, and overall safety. Clinical data concerning therapies based on cellular signals, while sometimes inconclusive, often yield outcomes comparable to or even superior to those of cell-based interventions. Nonetheless, both approaches face substantial challenges, including the need to ensure reproducibility of results, standardization of therapeutic product preparation, and addressing ethical and regulatory considerations. To translate these promising strategies into clinical practice, a greater number of large-scale, multicenter, and diverse clinical trials will be required.

Metabolic acidosis is a common complication of chronic kidney disease (CKD). The kidneys play a crucial role in acid–base balance, maintaining pH within the normal range (isohydria) by following mechanisms: bicarbonate reabsorption, ammogenesis, and titratable acidity. The anion gap describes the amount of unmeasured anions and is classically evaluated as the difference between the major cation (sodium) and the sum of the two major anions (chloride and bicarbonate). Metabolic acidosis can be divided into two types: normal anion gap metabolic acidosis and high anion gap metabolic acidosis. A high anion gap level is considered unfavorable in terms of prognosis as it is associated with increased mortality. Treatment of metabolic acidosis in patients with chronic kidney disease, despite available therapeutic options, is a challenge. Supplementation with bicarbonates does not improve prognosis on the one hand, and on the other hand, it may be harmful. The new KDIGO guidelines for 2024 have been significantly modified compared to 2012 after negative results of studies on bicarbonate supplementation. Bicarbonate supplementation is currently recommended only when levels are less than 18 mmol/L. This review provides an overview of the current knowledge on the pathophysiology, classification, and therapeutic options, including dietary recommendations and new pharmacology agents.