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.

Xanthine oxidase (XO) and aldehyde oxidase (AO) are molybdenum-dependent flavoenzymes involved in purine catabolism and hepatic xenobiotic metabolism. This study aimed to assess XO and AO activities and molybdenum (Mo) content in liver tissue from liver graft donors and recipients with end-stage liver failure (ESLF). Liver tissue samples were obtained from 10 liver donors (LD; control group) and 30 patients with ESLF undergoing liver transplantation. The ESLF cohort was further divided by primary liver disease: hepatitis B or C viral infection (HBV/HCV), alcohol-associated liver disease (ALD), primary sclerosing cholangitis (PSC), Wilson’s disease (WD), and primary biliary cholangitis (PBC). Enzymatic activity was determined by spectrofluorometry, and hepatic Mo content was measured by inductively coupled plasma mass spectrometry. Compared with LD controls, ESLF recipients showed a significant decrease in both hepatic XO activity and Mo content. At the subgroup level, XO activity was significantly reduced in ALD, PSC, and PBC, whereas HBV/HCV and WD showed lower but non-significant values. Mo content was significantly reduced in the overall ESLF cohort and in the WD subgroup, although disease-specific variability was observed, including relatively high Mo content in PSC. AO activity was assessed in a subset of samples and did not differ significantly between donor and recipient liver tissues. Correlation analyses did not demonstrate a statistically significant association between hepatic Mo content and XO activity, suggesting that total tissue Mo content may not directly reflect Mo-dependent enzymatic activity. These findings indicate that ESLF is associated with altered hepatic trace-element composition, including Mo, and with disturbances in Mo-dependent enzymatic activity. Future studies should combine liver tissue analysis with matched serum and portal blood samples to better characterise hepatic Mo metabolism and the systemic biological effects of trace elements.

Glioblastoma (GBM) is characterized by a profoundly immunosuppressive tumor microenvironment that limits the efficacy of conventional and immune-based therapies. Oncolytic herpes simplex virus (oHSV) therapy has emerged as a strategy capable of both tumor-selective infection and immune microenvironment modulation. This systematic review aimed to synthesize current evidence on how oHSV therapy reshapes the immunosuppressive microenvironment of GBM. A systematic search of PubMed (MEDLINE) and Embase identified original studies published between 2016 and 2025 investigating immunological or microenvironmental effects of oHSV-based therapies in GBM (final search: 28 January 2026). Preclinical and clinical studies were included, whereas reviews, editorials, conference abstracts, and studies of non-herpes oncolytic viruses were excluded. Study selection and data extraction were performed independently by two reviewers. Due to heterogeneity in models, viral constructs, and outcome measures, a qualitative narrative synthesis was conducted. Of 214 records, 22 studies met the inclusion criteria. Most were preclinical studies using orthotopic immunocompetent murine models, with limited clinical evidence including an early-phase trial in recurrent high-grade glioma. Therapeutic efficacy frequently correlated with tumor microenvironment remodeling rather than viral replication alone. oHSV infection promoted inflammatory signaling, antigen presentation, macrophage polarization, and effector T-cell recruitment but also induced counter-regulatory mechanisms such as myeloid-mediated immunosuppression and vascular or stromal barriers. The clinical significance and durability of these effects remain to be established in larger prospective studies. Despite heterogeneous designs and limited clinical data, current evidence suggests that oHSV may function as a platform for immune microenvironment reprogramming in glioblastoma.