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This study investigated the role of brain-derived neurotrophic factor (BDNF) in patients with degenerative lumbar stenosis, focusing on its expression and correlation with pain intensity. The study examined 96 patients with lumbar stenosis and 85 control participants. BDNF levels in the yellow ligamentum flavum were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot analysis. The results showed significantly higher BDNF expression at both messenger ribonucleic acid (mRNA; fold change = +1.35 ± 0.23; p < 0.05) and protein levels in patients (28.98 ± 6.40 pg/mg) compared to controls (4.56 ± 1.98 pg/mg; p < 0.05). Furthermore, BDNF levels correlated positively with pain intensity reported by patients, with higher expression observed in those experiencing more severe pain. The study also explored the influence of lifestyle factors, such as smoking and alcohol consumption, and related diseases, such as diabetes, on BDNF expression. Smoking, alcohol use, and diabetes were associated with significantly elevated BDNF levels (p < 0.05). These findings suggest that BDNF could serve as a biomarker for pain severity in degenerative lumbar stenosis at the protein level, although this was not consistently observed at the mRNA level; this highlights the potential for BDNF-targeted therapies in managing pain. Future research should involve larger longitudinal studies to validate these findings and explore therapeutic interventions. This study underscores the importance of considering molecular and lifestyle factors in the treatment of degenerative lumbar stenosis, aiming to improve patient outcomes through comprehensive, targeted approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the role of circadian clock genes in the progression of astrocytic tumors, a common type of brain tumor. We aimed to understand how these genes, which control the body's daily rhythms, behave differently in low-grade versus high-grade tumors. Our findings reveal that certain circadian clock genes are more active in advanced tumor stages, potentially driving tumor growth. Additionally, we discovered that changes in DNA methylation and microRNAs might regulate these genes. Understanding these molecular changes could help identify new biomarkers for tumor diagnosis and progression, offering new avenues for targeted treatments. This research provides valuable insights into the complex biology of brain tumors and highlights the importance of circadian genes in the development of cancer. 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. [ABSTRACT FROM AUTHOR]

The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1–3 (TGF-β-1–3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of TGF-β-1 and TGF-β-3, while TGF-β-2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-β-1, TGF-β-2, and TGF-β-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-β-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; p < 0.0001), TGF-β-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; p < 0.0001), TGF-β-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, p < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-β-1–3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-β-1–3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-β isoforms level for better understanding and managing degenerative spinal conditions. [ABSTRACT FROM AUTHOR]

Introduction: Unhealthy habits such as overeating processed and high-calorie foods, alcohol abuse, and smoking negatively impact human health. It has been suggested that the inflammatory process and the resulting growth of nerve fibers within the intervertebral disc (IVD) fissures is the main reason for the pain accompanying IVD degeneration (IVDD). Aim: The aim of this study was to determine whether smoking, alcohol consumption, overweight/obesity, or diabetes comorbidity contribute to the development of IVDD and how the aforementioned factors affect the levels of brain-derived neurotrophic factor (BDnF), glial cell-derived neurotrophic factor (GDnF), and growth associated protein 43 (GAP-43) in the study and control groups. Material and methods: The study group comprised 113 patients diagnosed with IVDD who qualified for microdiscectomy. Control group included 81 IVDs obtained from Caucasian human cadavers. The expression profiles of BDnF, GDnF, and GAP-43 were determined by enzyme-linked immunosorbent assay (ELISA). Results: Our statistical analysis confirmed that patients who were overweight/obese, smoked tobacco, consumed alcohol, or had diabetes had a higher risk of IVDD (OR>1). Statistical analysis showed that BDnF, GAP-43, and GDnF concentrations were significantly higher in the IVDs obtained from the study group compared with the control group (p<0.05). In addition, higher levels of BDnF, GDnF, and GAP-43 were noted in IVDD patients who consumed alcohol, smoked tobacco, were overweight/obese, or had comorbid diabetes compared with patients without these risk factors (p<0.05). Conclusions: We showed that changes in energy metabolism, habits, and lifestyle as well as the degenerative process of IVD in the lumbosacral spine contribute to changing the concentration profile of the analyzed neurotrophic factors. [ABSTRACT FROM AUTHOR]

Introduction: The clinical manifestation of degenerative stenosis of the lumbosacral (L/S) spine also has a molecular basis. Aim: The study investigates molecular changes in the L/S spine's ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-α1-3). Material and methods: Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). Results: At the mRnA level, study samples showed reduced expression of TGF-α1 and TGF-α3, while TGF-α2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-α1, TGF-α2, and TGF-α3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-β1 was observed (2139.33 pg/ml±2593.72 pg/ml vs. 252.45 pg/ml±83.89 pg/ml; p<0.0001), TGF-α2 (3104.34 pg/ml±1192.74 pg/ml vs. 258.86 pg/ml±82.98; p<0.0001), TGF-α3 (512.75 pg/mL±107.36 pg/mL vs. 55.06 pg/mL±9.83 pg/mL, p<0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-α1-3 concentrations and pain severity. Conclusions: The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-α1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-α isoform level for better understanding and managing degenerative spinal conditions. [ABSTRACT FROM AUTHOR]

Introduction: It effectively communicates the importance of evaluating changes in the concentration profiles of micronutrients and macronutrients in the intervertebral disc (IVD) in the context of osteoarthritis for identifying enzymes and metabolites involved in the degenerative process of the IVD. Aim: This study aimed to evaluate changes in the concentrations of copper (Cu), iron (Fe), manganese (Mn), lead (Pb), zinc (Zn), sodium (na), potassium (K), phosphorus (P), calcium (Ca), and magnesium (Mg) in the degenerative process of the lumbar/sacral (L/S) IVD segment. Material and methods: The study group comprised 180 patients scheduled for microdiscectomy due to degenerative L/S IVD segments. Additionally, 90 individuals from the Caucasian Council were included in the control group, with post-mortem card collection from the L/S section of the circle. Results: Chemical analysis revealed significantly higher zinc (Zn) concentrations in study group samples compared to control samples (32.95 mg/kg DM ±21.55 mg/kg DM vs. 21.26 mg/kg DM ±13.86 mg/kg DM). Phosphorus (P) levels were also significantly higher in study group samples (4968.45 mg/kg DM ±5469.92 mg/kg DM vs. 1543.80 mg/kg DM ±1332.49 mg/kg DM), as well as calcium (Ca) (6012.25 mg/kg DM ±13884.34 mg/kg DM vs. 1451.45 mg/kg DM ±722.63 mg/kg DM). One-way AnOVA analysis indicated that the changes in iron (Fe), manganese (Mn), sodium (na), and magnesium (Mg) significantly correlated with the degree of IVD degeneration. Conclusions: The altered profiles of zinc (Zn), magnesium (Mg), calcium (Ca), and phosphorus (P) concentrations characterize the degenerative process of the L/S IVD segment. Assessing changes in iron (Fe), manganese (Mn), sodium (na), and magnesium (Mg) levels may aid in evaluating the progression of degenerative changes in the L/S IVD segment. However, micro- and macronutrient variations did not significantly correlate with the severity of pain in the L/S segment of the spine. [ABSTRACT FROM AUTHOR]

Introduction: The role of Brain-Derived neurotrophic Factor (BDnF) in intervertebral disc degeneration may contribute to the pathogenesis of lumbosacral stenosis through its influence on neuronal survival and synaptic plasticity within the spinal canal. Aim: The aim of this study was to determine the differences in expression profiles of BDnF in IVD degeneration and L/S stenosis. Material and methods: The study group comprised 113 patients diagnosed with IVDD who qualified for microdiscectomy. The comparison group included 60 patients with L/S stenosis. The expression profiles of BDnF were determined by enzyme-linked immunosorbent assay (ELISA). Results: The concentration of BDnF in the IVD of patients was 17.91pg/mL ±19.58 pg/mL, while in the yellow ligament of patients with L/S spinal degenerative stenosis was 4.97 pg/mL ±0.25 pg/m (p<0.05). Conclusions: In conclusion, our study highlights significant differences in the expression profiles of Brain-Derived neurotrophic Factor (BDnF) between intervertebral disc degeneration (IVDD) and lumbosacral (L/S) spinal degenerative stenosis. We found that the concentration of BDnF in the intervertebral discs of patients with IVDD was notably higher compared to that in the yellow ligament of patients with L/S stenosis. This suggests a potential role of BDnF in the pathogenesis of IVDD, possibly through its influence on neuronal survival and synaptic plasticity within the spinal canal. These findings shed light on the molecular mechanisms underlying spinal degenerative disorders and may pave the way for targeted therapeutic interventions aimed at modulating BDnF expression to mitigate disc degeneration and associated symptoms. Further research is warranted to elucidate the exact mechanisms by which BDnF contributes to these pathologies and to explore its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

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-1β, 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In the treatment of moderate to severe psoriasis, cyclosporine A (CsA) conventional therapy is used and biological, anti-cytokine treatment using, for example, anti-TNF drug-adalimumab., Aim: This study aimed at investigating the effect of CsA and adalimumab on the profile of mRNAs and protein expression associated with transforming growth factor β (TGF β ) pathways in human keratinocyte (HaCaT) culture previously exposed to lipopolysaccharide (LPS)., Materials and Methods: HaCaT culture was exposed to 1 ng/ml LPS for 8 hours+8  μ g/ml adalimumab for 2, 8, and 24 hours or 1 ng/ml LPS for 8 hours+100 ng/ml CsA for 2, 8, and 24 hours and compared to the control culture. Sulphorodamine B cytotoxicity assay was performed. The expression profile of mRNA related to TGF β paths was indicated by microarray and RTqPCR analyses. The ELISA test was used to analyze changes on the proteome level. Statistical analysis consisted of ANOVA analysis and the post hoc Tukey test ( p < 0.05)., Results: The cytotoxicity test showed that LPS, adalimumab, and cyclosporine in the concentration used in this experiment did not have any cytotoxicity effect on HaCaT cells. The largest fold changes (FC) in expression in (∣FC | >4.00) was determined for TGFβ1-3 , TGFβRI-III , SKIL , SMURF2 , SMAD3 , BMP2 , BMP6 , JAK2 , UBE2D1 , SKP2 , EDN1 , and PRKAR2B ( p < 0.05). In addition, on the protein level, the direct changes observed at mRNA were the same., Conclusion: Analysis of the microarray expression profile of genes associated with TGF β signaling pathways has demonstrated the potential of cyclosporin A and adalimumab to induce changes in their transcriptional activity. The anti-TNF drug seems to affect TGF β cascades to a greater extent than cyclosporin A. The obtained results suggest that the regularity of taking the drug is important for the efficacy of psoriasis therapy., Competing Interests: The authors declare no conflict of interest, financial, or otherwise., (Copyright © 2020 Iwona Adwent et al.)