Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors.

This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications.

A Study of 179 Patients with Degenerative Stenosis of the Lumbosacral Spine to Evaluate Differences in Quality of Life and Disability Outcomes at 12 Months, Between Conservative Treatment and Surgical Decompression.

BACKGROUND This prospective study included 179 patients with degenerative stenosis of the lumbosacral spine and aimed to evaluate the outcomes of conservative treatment and surgical decompression on quality of life and disability over 12 months. MATERIAL AND METHODS The surgery group consisted of 96 patients with degenerative stenosis of the lumbosacral spine who qualified for surgical decompression, while the conservative-treatment group included 83 patients who qualified for conservative treatment. We used the Satisfaction with Life Scale questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, the Visual Analog Scale to assess the severity of pain, the Oswestry Low Back Pain Disability Questionnaire to assess the degree of disability, and the Sexual Satisfaction Scale at 0, 1, 6, and 12 months after treatment. RESULTS Statistical analysis showed a positive relationship between conservative and surgical treatment and quality of life (P<0.05). A significant reduction in the severity of pain (P<0.05) and the degree of disability (P<0.05) were both recorded during the 12-month followup period in both groups. Women of both groups declared significantly lower satisfaction than men at every time point (P<0.05). CONCLUSIONS Most patients in both groups declared an improvement in their quality of life, with the surgery group showing a higher percentage of responses that their quality of life had improved. Based on the results obtained from the FACIT-F questionnaire, degenerative stenosis of the lumbosacral spine had a non-root effect on the patients' lives in the surgery group.

Evaluation of the concentration of growth associated protein-43 and glial cell-derived neurotrophic factor in degenerated intervertebral discs of the lumbosacral region of the spine.

Important neurotrophic factors that are potentially involved in degenerative intervertebral disc (IVD) disease of the spine's lumbosacral (L/S) region include glial cell-derived neurotrophic factor (GDNF) and growth associated protein 43 (GAP-43). The aim of this study was to determine and compare the concentrations of GAP-43 and GDNF in degenerated and healthy IVDs and to quantify and compare the GAP-43-positive and GDNF-positive nerve fibers. The study group consisted of 113 Caucasian patients with symptomatic lumbosacral discopathy (confirmed by a specialist surgeon), an indication for surgical treatment. The control group included 81 people who underwent postmortem examination. GAP-43 and GDNF concentrations were significantly higher in IVD samples from the study group compared with the control group, and the highest concentrations were observed in the degenerated IVDs that were graded 4 on the Pfirrmann scale. In the case of GAP-43, it was found that as the degree of IVD degeneration increased, the number of GAP-43-positive nerve fibers decreased. In the case of GDNF, the greatest number of fibers per mm2 of surface area was found in the IVD samples graded 3 on the Pfirrmann scale, and the number was found to be lower in samples graded 4 and 5. Hence, GAP-43 and GDNF are promising targets for analgesic treatment of degenerative IVD disease of the lumbosacral region of the spine.

Presentation, Diagnosis, and Management of Lower Back Pain Associated with Spinal Stenosis: A Narrative Review.

Lower back pain (LBP) is an extremely common symptom experienced by people of all ages and is also one of the most frequent causes of disability worldwide. This article aims to review the presentation, diagnosis, and management of lower back pain associated with spinal stenosis. The paper we prepared was classified as a "literature narrative review." Nonetheless, when searching for manuscripts included in our work and reviewing them critically, we concentrated on the keywords: "lower back pain", "lumbar spine stenosis", "diagnostic", "rehabilitation", "neurosurgery", "spine", and "elderly". The incidence of chronic lower back pain (CLBP) increases linearly starting with the third decade of life until 60 years old, and it more often affects women. The course of non-specific LBP above all depends on factors not connected with the spine, which include psychological, behavioral, and social factors, determined by the way the condition is perceived by the patient the environment. Lumbar spine stenosis (LSS) is an age-related process of degeneration of the intervertebral discs, ligamentum flavum, and facet joints, which results in narrowing of the space around the neurovascular structures of the spine. Diagnosis of spinal pain syndromes includes radiography (RTG), computed tomography (CT), and magnetic resonance imaging (MRI). Based on the results of imaging studies, neurological examination, and the severity of the disease, treatment can consist of analgesics and rehabilitation, or, when conservative methods are insufficient, surgical treatment is indicated.

Usefulness of Detecting Brain-Derived Neurotrophic Factor in Intervertebral Disc Degeneration of the Lumbosacral Spine.

BACKGROUND In determining the etiology of pain of discogenic origin, attention is paid to the role of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF). Considering the potential role of BDNF in the etiology of pain during intervertebral disc degeneration (IVDD), this study aimed to assess changes in the number of BDNF-positive nerve fibers and levels of BDNF in IVDD of the lumbosacral spine in comparison to intervertebral discs (IVDs) of the control group (cadavers). MATERIAL AND METHODS The study group comprised 113 patients with IVDD of the lumbosacral spine. The control group consisted of 81 people (cadavers). We performed hematoxylin-eosin staining to assess IVD structures (degeneration), immunohistochemistry to determine the number of BDNF-positive nerve fibers, and an enzyme-linked immunosorbent assay and western blot to quantify BDNF levels in IVDs. RESULTS Levels of BDNF in the study group were significantly higher than in the control group (17.91±19.58 pg/mg; P<0.05). Furthermore, BDNF levels were significantly higher in the annulus fibrosus compared to the nucleus pulposus of the intervertebral disc (5.50±6.40 pg/mg; P<0.05). Neither the number of BDNF-positive nerves (P=0.359) nor BDNF concentration (P=0.706) were significantly correlated with the degree of perceived pain. The number of BDNF-positive fibers per 1 mm2 was not found to differ significantly according to the radiological degree of degeneration of the lumbosacral spine based on the Pfirrmann scale (P=0.735). CONCLUSIONS The level of BDNF expression may be indicative of IVD degeneration, although it does not predict the degree of this degeneration.

Pathomechanism of the IVDs Degeneration and the Role of Neurotrophic Factors and Concentration of Selected Elements in Genesis of Low Back Pain.

Degenerative disc disease of the lumbosacral spine is a very common medical problem. An episode of sciatica occurs at least once in the life of 60-90% of the human population. A phenomenon that is closely related to the process of lowering the pH of the extracellular matrix degenerating the intervertebral disc (IVD) is the precipitation of calcium salts, especially pyrophosphate dehydrate and hydroxyapatite. In such an altered environment of the IVD, we can observe an increased influx of monocytes, macrophages, T-lymphocytes, as well as non-immunocompetent cells, which are a source of cytokines, e.g., tumor necrosis alpha (TNF-α), interleukin- (IL-1ß, IL-8). The above-mentioned mediators of an inflammatory condition contribute to an increase in the expression of Brain-Derived Neurotrophic Factor (BDNF) and Glial cell Derived Neurotrophic Factor (GDNF) in mast cells and chondrocytes, as well as to the descending transport of these mediators along the nerve endings. In the process of degeneration of the IVD as a result of repeated and even slight injuries, there is damage to the connections of the endplate of the vertebral bodies with the IVD, which results in an impairment of the penetration of nutritional substances and water into the disc. As a consequence, there is an overexpression of the brain-derived neurotrophic factor GDNF, as well as neuromodulin (GAP-43) in the mast cells and chondrocytes of the IVDs, while descending transport of these mediators along the nerve fibers is also observed.

Changes in Elements and Relationships among Elements in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a complex and progressive process of disc aging. One of the most important causes of changes in the internal environment, leading to IVDD, can be changes in the concentration of individual metal elements. This study aimed to analyze the concentrations of copper, iron, manganese, lead, zinc, sodium, potassium, phosphorus, and calcium in the degenerated intervertebral discs of the lumbosacral spine, compared to healthy intervertebral discs. The study group (S) consisted of 113 Caucasian patients, qualified by a specialist surgeon for IVDD of the lumbosacral spine. The control group (C) consisted of 81 individuals. The biological material was obtained from Caucasian human cadavers during post-mortem examination. The concentrations of individual elements were assessed using inductively coupled plasma−optical emission spectroscopy (ICP-OES). Statistically significant differences in the concentrations of microelements, depending on the degree of pain intensity, were noted for only potassium (p < 0.05). Statistically significant differences in the concentrations of the assessed microelements, depending on the degree of radiological advancement of the lesions, were noted for copper and iron (p < 0.05). In the degenerated intervertebral discs, the strongest relationships were noted between the concentrations of zinc and lead (r = 0.67; p < 0.05), zinc and phosphorus (r = 0.74; p < 0.05), and zinc and calcium (r = 0.77; p < 0.05). It has been indicated that, above all, the concentrations of copper and iron depend on the advancement of radiological changes, according to the Pfirrmann scale; however, no influence on the pain intensity, depending on the concentration of the assessed elements, was found.