Aleksandra Wyczałkowska-Tomasik

Intervertebral disc degeneration is a leading contributor to chronic back pain and disability worldwide. This review comprehensively explores the complex interplay of cellular, molecular, and biomechanical alterations within the disc microenvironment that underlie intervertebral disc degeneration pathophysiology. Emphasis is placed on extracellular matrix degradation, cellular senescence, inflammation, oxidative stress, angiogenesis, and multiple forms of programmed cell death including apoptosis, pyroptosis, and ferroptosis. An in-depth analysis of key signaling pathways and regulatory molecules illustrates how these processes disrupt homeostasis and drive disease progression. Additionally, the review highlights emerging therapeutic approaches aimed at modifying the disc microenvironment, including mesenchymal and notochordal cell-based therapies, senolytics, ferroptosis inhibitors, gene therapy, and biomaterial innovations such as hydrogels, scaffolds, and nanocarriers. These strategies target degenerative cascades at the molecular level and represent a shift toward regenerative and disease-modifying interventions. While several approaches show promise in preclinical and early clinical studies, challenges related to safety, delivery, and long-term efficacy remain. This review underscores the importance of integrating molecular insights with translational innovations to develop targeted therapies for intervertebral disc degeneration and guide future research efforts.

Background: The chronic kidney disease (CKD) population, including kidney transplant recipients (KTRs) and subjects on renal replacement therapy, is particularly vulnerable to unfavorable outcomes from chronic hepatitis C (CHC). Currently, there are oral direct-acting antiviral agents (DAAs) available to eradicate the virus with favorable short-term outcomes; however, their long-term effects are lacking. The aim of the study is to assess the long-term efficacy and safety of DAA therapy in the CKD population. Methods: An observational, cohort single-center study was performed. Fifty-nine CHC subjects with CKD, treated with DAAs between 2016 and 2018, were enrolled in the study. Safety and efficacy profiles were assessed, including sustained virologic response (SVR), occult hepatitis C infection (OCI) incidence, and liver fibrosis. Results: SVR was achieved in 96% of cases (n = 57). OCI was diagnosed only in one subject following SVR. Significant liver stiffness regression was observed 4 years after SVR compared to baseline values (Mdn = 6.1 kPa, IQR = 3.75 kPa; 4.9 kPa, IQR = 2.9 kPa), p < 0.001. The most common adverse events were anemia, weakness, and urinary tract infection. Conclusion: DAAs provide a safe and effective cure for CHC in both CKD patients and KTRs with a favorable safety profile in the long-term follow-up.