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    The effects of rivaroxaban, an oral anticoagulant, on human IVD primary cultures
    (Termedia Publishing House Ltd, 2022) Caliskan, Tezcan; Akalan, Hande; Yilmaz, Ibrahim; Karaarslan, Numan; Sirin, Duygu Yasar; Özbek, Hanefi
    Introduction: The present study aimed to investigate the potential effects of rivaroxaban, an oral anticoagulant that inhibits the effects of factor Xa, on intact intervertebral disc tissue cells and the extracellular matrix (ECM). Material and methods: Rivaroxaban was applied to primary human cell cultures prepared from tissues of the intervertebral disc. Comparative molecular analyses were performed on non-drug-treated control group samples. Descriptive statistics were presented as the mean +/- standard deviation. An analysis of variance test was performed to determine whether there were significant differences in the mean across the groups. When differences across groups were observed, Tukey's honestly significant difference post-hoc test was used for multiple pairwise comparisons. The significance of the obtained data was determined statistically. The alpha significance value was < 0.05. Results: The cells in the control group and in the rivaroxaban-treated group were viable, healthy, and proliferated (p < 0.05). However, the expression levels of the chondroadherin gene (CHAD), cartilage oligo matrix protein (COMP), matrix metalloproteinase (MMP)-13, and MMP-19 genes were changed (p < 0.05). Conclusions: Although rivaroxaban does not suppress cell proliferation due to morphological, biological, and biochemical changes in the intervertebral disc tissue, it may change the expression of genes that are related to ECM maintenance.
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    Is favipiravir a potential therapeutic agent in the treatment of intervertebral disc degeneration by suppressing autophagy and apoptosis?
    (Turkish Neurosurgical Soc, 2022) Yılmaz, İbrahim; Akalan, Hande; Şirin, Duygu Yaşar; Karaarslan, Numan; Özbek, Hanefi; Ateş, Özkan
    AIM: To evaluate the effects of favipiravir (FVP) on cell viability and cytotoxicity in human degenerated primary intervertebral disc (IVD) tissue cell cultures. Furthermore, the protein expressions of hypoxia-inducible factor 1 alpha (HIF-1 alpha), nuclear factor-kappa-b (NF-kappa B), and interleukin-1 beta (IL-1 beta) were also examined. MATERIAL and METHODS: Untreated cell cultures served as the control group, named group 1. Cell cultures treated with FVP served as the study group, named group 2. Pharmacomolecular analyses were performed in all groups at 0, 24, 48, and 72 hours (h). Obtained data were evaluated statistically. RESULTS: Cell proliferation was suppressed in the FVP-treated samples compared to the control group samples at 24 and 72 h, and this was statistically significant (p<0.05). Decreased or increased protein expression levels of HIF-1 alpha, NF-kappa B, and IL-1 beta in FVP-treated samples may be an indication of suppression in anabolic events as well as proliferation in IVD cultures. FVP administration showed that AF/NP cells in a culture medium may induce a strong inflammatory response to FVP. This strong inflammatory response is likely to cause slowed proliferation. It may also be a trigger for many catabolic events. NF-kappa B expression increased within the first 24 h and then decreased rapidly. Based on the data obtained, it may be suggested that the rapidly increasing NF-kB may have stimulated the expression of many antiproliferative genes. CONCLUSION: The suppression of IL-1 beta and NF-kB protein expressions in IVD cells treated with FVP is important in the treatment of IVD degeneration (IDD). If the protein expression of HIF-1 alpha could be increased along with the suppression of IL-1 beta and NF-kB, FVP would perhaps be a promising pharmacological agent in the treatment of IDD.