Chronic inflammation is increasingly recognized as a driver of glioma progression, with tumor necrosis factor-alpha (TNF-α) playing a central role in modulating the tumor microenvironment. This study aimed to investigate the expression profiles and regulatory mechanisms of TNF-α and its downstream mediators—including interleukin-1 beta (IL-1β), Mitogen-Activated Protein Kinase Kinase Kinase 8 (MAP3K8), and Mitogen-activated protein kinase kinase 7 (MAP2K7)—in astrocytic tumors of varying malignancy. We conducted an integrative molecular analysis of 60 human astrocytic tumor samples (20 G2, 12 G3, 28 G4) using transcriptomic microarrays, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR), Enzyme-Linked Immunosorbent Assay (ELISA), Western blotting, immunohistochemistry, methylation-specific PCR, and miRNA profiling. Prognostic associations were evaluated using Kaplan–Meier survival and Cox regression analyses. TNF-α, IL-1β, and MAP3K8 were significantly upregulated in high-grade tumors, with log₂ fold changes ranging from 5.56 to 8.76 (p < 0.001). High expression of TNF-α (HR = 2.10, 95% CI: 1.27–3.46, p = 0.004), IL-1β (HR = 2.35, 95% CI: 1.45–3.82, p = 0.001), and MAP3K8 (Hazard Ratio; HR = 1.88, 95% confidence interval; 95% CI: 1.12–3.16, p = 0.015) was associated with poorer overall survival. miR-34a-3p and miR-30 family members, predicted to target TNF-α and IL-1β, were markedly downregulated in G3/G4 tumors (e.g., miR-30e-3p fold change: –3.78, p < 0.01). Promoter hypomethylation was observed in G3/G4 tumors, supporting epigenetic activation. Our findings establish a multi-layered regulatory mechanism of TNF-α signaling in astrocytic tumors. These data highlight the TNF-α/IL-1β/MAP3K8 axis as a critical driver of glioma aggressiveness and a potential therapeutic target.

Background/Objectives: Degenerative lumbo-sacral spinal stenosis is characterized by spinal canal narrowing, often linked to ligamentum flavum hypertrophy. This study evaluated the elemental composition of ligamentum flavum tissue in DLSS patients compared to healthy controls. Methods: This study involved 180 patients diagnosed with degenerative lumbo-sacral spinal stenosis and 102 healthy controls. Ligamentum flavum samples were analyzed for concentrations of magnesium (Mg), calcium (Ca), phosphorus (P), zinc (Zn), copper (Cu), iron (Fe), sodium (Na), potassium (K), manganese (Mn), and lead (Pb) using inductively coupled plasma optical emission spectrometry (ICP-OES). Statistical analyses were conducted using Student’s t-test, ANOVA, and Pearson’s correlation, with a significance threshold of p < 0.05. Results: The study group exhibited significantly elevated levels of Mg (p < 0.001), Ca (p = 0.014), and P (p = 0.006), along with reduced concentrations of Zn (p = 0.021) and Cu (p = 0.038) compared to controls. No statistically significant differences were observed for Na, K, Mn, or Fe (p > 0.05). Elemental imbalances were more pronounced in individuals with higher body mass index (BMI) and varied by gender. Pain intensity demonstrated a significant correlation with Zn (p = 0.012) and Na (p = 0.045), but no consistent associations with Mg, Ca, or P. Conclusions: Altered Mg, Ca, P, and Zn levels in ligamentum flavum suggest their involvement in degenerative lumbo-sacral spinal stenosis pathophysiology. These elements may serve as potential biomarkers and therapeutic targets for mitigating spinal canal narrowing.

Background/Objectives: Lumbosacral spinal stenosis (LSS) is a degenerative condition characterized by narrowing of the spinal canal and associated neuropathic pain. While mechanical compression is well-characterized, the molecular mechanisms contributing to symptom severity remain poorly understood. Neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor family, has emerged as a potential mediator of neural plasticity and nociception, but its role in spinal stenosis is largely unexplored. Methods: We analyzed NRTN mRNA and protein expression in ligamentum flavum samples from 96 patients undergoing surgery for LSS and 85 non-degenerative postmortem controls. Quantification was performed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. Pain severity Visual Analog Scale (VAS), body mass index (BMI), diabetes, smoking, and alcohol use were assessed as modulators of NRTN expression. Results: NRTN expression was significantly elevated in LSS patients versus controls at both transcript and protein levels (p < 0.05). NRTN levels positively correlated with pain intensity (VAS; ANOVA p = 0.032 for mRNA, p = 0.041 for protein). Multivariate regression identified BMI (β = 0.50, p = 0.015) and diabetes (β = 0.39, p = 0.017) as independent predictors of increased NRTN expression. Alcohol use also showed a positive association (p = 0.046), while smoking showed no significant independent effect. Conclusions: Neurturin is upregulated in ligamentum flavum tissue from LSS patients and correlates with pain severity and metabolic risk factors. These findings suggest NRTN as a potential biomarker and therapeutic target in degenerative spine disease. Further longitudinal and mechanistic studies are warranted to elucidate its role in chronic pain and neuroinflammation.

Degenerative lumbosacral spinal stenosis (DLSS) is a progressive condition characterized by narrowing of the spinal canal and subsequent neural compression, often leading to chronic pain and disability. Neurotrophins, particularly neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4), play essential roles in maintaining neuronal integrity and modulating nociceptive signaling; however, their involvement in DLSS and potential modulation by systemic and behavioral factors remain poorly understood. This study evaluated NT-3 and NT-4 expression in ligamentum flavum (LF) tissue from 96 patients undergoing surgical decompression for DLSS and compared the results to 85 postmortem control samples. Quantitative analyses were performed using RT-qPCR, ELISA, and immunohistochemistry. NT-3 transcript levels were markedly elevated in stenotic LF samples (fold change: 9.12 ± 0.56; p < 0.05), while NT-4 mRNA expression was significantly reduced (fold change: 0.33 ± 0.07; p < 0.05). At the protein level, both NT-3 (134 ± 5.78 pg/mL) and NT-4 (316.77 ± 8.19 pg/mL) concentrations were significantly increased compared to controls (p < 0.05). Although neurotrophin levels did not correlate directly with pain intensity or morphological severity, elevated NT-3 and NT-4 protein levels were significantly associated with obesity, diabetes, alcohol consumption, and tobacco use (p < 0.05). These findings demonstrate that NT-3 and NT-4 are differentially expressed in the ligamentum flavum of patients with DLSS and are influenced by systemic metabolic disturbances and lifestyle factors, suggesting their potential as biomarkers or therapeutic targets in degenerative spinal disease.

Background/Objectives: Degenerative spinal conditions, such as degenerative stenosis, have been linked to metabolic and lifestyle factors, including obesity, smoking, and diabetes. Glial cell line-derived neurotrophic factor (GDNF) plays a crucial role in neuroprotection, but its relationship with these risk factors remains unclear. Methods: This study aims to evaluate the relationship between body mass index (BMI), smoking, diabetes, and GDNF levels in patients with degenerative spine conditions. We measured the GDNF levels in patients with degenerative stenosis and assessed the impact of BMI, smoking status, and the presence of diabetes. Comparisons were made using appropriate statistical analyses to determine the significance of these factors on GDNF levels. Results: A significant inverse relationship was observed between the BMI and GDNF levels (p < 0.01). Patients with a higher BMI exhibited lower GDNF concentrations. Additionally, patients who smoked or had diabetes showed significantly lower GDNF levels compared to non-smokers and those without diabetes (p = 0.03 and p = 0.02, respectively). These findings suggest that both metabolic and lifestyle factors are associated with decreased GDNF, which may accelerate neurodegenerative processes in the spine. Conclusions: Our study demonstrates that increased BMI, smoking, and diabetes are linked to reduced GDNF levels, potentially contributing to the progression of degenerative spine conditions such as stenosis. These findings highlight the need for targeted clinical interventions to manage these risk factors, aiming to preserve GDNF levels and slow the degenerative processes in the spine. Future research should explore therapeutic approaches to modulate GDNF in affected populations.

Background: Cervical radiculopathy is a common and disabling condition with both nociceptive and neuropathic pain components. Epidural steroid injections (ESIs) are widely used as an interventional treatment modality; however, the optimal cervicothoracic interlaminar access level and injectate volume remain subjects of ongoing debate. Because injection level and injectate volume have historically been varied together in routine practice rather than independently, prospectively designed comparative data are lacking. Methods: In this retrospective, multicenter cohort study, 166 patients with MRI-confirmed cervical radiculopathy treated between January 2022 and December 2025 at three participating institutions received fluoroscopy-guided cervicothoracic interlaminar epidural steroid injections with dexamethasone and bupivacaine at either C7/T1 (6 mL; n = 87) or T1/T2 (8 mL; n = 79), with protocol determined by the treating institution rather than randomization. The prespecified primary outcome was the baseline-adjusted between-group difference in arm-pain Numeric Rating Scale (NRS) score at 3 months, analyzed by analysis of covariance (ANCOVA) adjusted for a directed acyclic graph-informed covariate set (age, symptom duration, baseline pain severity, number of stenotic levels, DN4 score, and treatment center); the same covariates were used in a generalized estimating equation (GEE) model with a group-by-time interaction and in a multivariable logistic regression for treatment response. Secondary outcomes—neck-pain NRS and VAS, neuropathic pain (DN4), functional disability (NDI), quality of life (SF-36, EQ-5D), Patient Global Impression of Change (PGIC), analgesic consumption, and cardiovascular/metabolic safety outcomes—were assessed at baseline, 3 months, and 6 months. Results: Both groups showed significant within-group reductions in arm-pain NRS (C7/T1: 8.7 ± 0.4 to 3.5 ± 0.4 at 3 months and 4.1 ± 0.6 at 6 months; T1/T2: 9.2 ± 0.7 to 3.9 ± 0.5 at 3 months and 4.9 ± 0.7 at 6 months; both p < 0.001). Baseline pain scores and symptom duration were not balanced between groups (baseline-adjusted analysis was therefore used). After adjustment for baseline severity, age, symptom duration, and center, the T1/T2–8 mL protocol was associated with higher (worse) adjusted arm-pain NRS than the C7/T1–6 mL protocol at 3 months (adjusted difference 0.41 points, 95% CI 0.21–0.61) and 6 months (0.66 points, 95% CI 0.35–0.97); a multivariable-adjusted logistic regression model likewise showed lower odds of achieving a ≥50% arm-pain reduction at 3 months with the T1/T2–8 mL protocol (adjusted OR 0.18, 95% CI 0.04–0.82). NDI decreased from a mean of 48.1 points at baseline to 28.1 points at 3 months (pooled cohort, score capped at the 0–50 scale maximum; the majority of baseline NDI source records could not be individually verified and this is reported as a limitation), and analgesic consumption decreased over follow-up. Among hypertensive patients (45/166, 27.1%), 78% experienced transient blood pressure elevation and 40% required temporary antihypertensive adjustment; among diabetic patients (13/166, 7.8%), 92% developed transient hyperglycemia. Because injection level, injectate volume, and treatment center were confounded by design, these findings should be interpreted as a comparison of two center-specific treatment protocols rather than an isolated effect of anatomical level or volume. Conclusions: Both center-specific cervicothoracic interlaminar epidural steroid injection protocols were associated with improvements in pain and function over six months, with no catastrophic procedural complications documented; however, near-complete confounding of injection level with injectate volume and treatment center, together with imbalanced baseline pain severity, precludes conclusions about the comparative effectiveness of C7/T1 versus T1/T2 access. Transient cardiovascular and metabolic effects were common and support consideration of post-procedural monitoring in patients with pre-existing hypertension or diabetes.