Sürdürülebilir Kalkınma Amaçları

• 2

• MakaleAçık Erişim2026Scopus SJRQ1/r/bayburt/16798
  Pomegranate Peel Extract and Punicalagin Are Associated with Attenuated Intestinal Barrier Dysfunction, Oxidative Stress, and Multi-Organ Injury in a Rat CLP Model

  Yeni, M; Ürüşan, H; Bayraktar, B; Kotan, GC

  • 
  İncele
• MakaleAçık Erişim2025Scopus SJRQ1/r/bayburt/12766
  Disrupted miRNA Biogenesis Machinery Reveals Common Molecular Pathways and Diagnostic Potential in MDS and AML

  Çevik, Kenan; Ay, Mustafa Ertan; Tombak, Anıl; Ay, Özlem İzci; Karakaş, Ümit; Erdal, Mehmet Emin

  Background: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal stem cell disorders in which disrupted post-transcriptional regulation contributes to aberrant hematopoiesis and leukemic transformation. The miRNA biogenesis machinery, which comprises Drosha, DGCR8, Dicer, TARBP2, and AGO1, ensures the precise maturation of miRNAs that control lineage commitment and proliferation. However, the extent to which alterations in this pathway reshape hematopoietic gene networks during myeloid disease evolution remains largely unexplored. Methods: Bone marrow samples from newly diagnosed, untreated MDS and AML patients and matched healthy controls were analyzed for the expression of five key miRNA biogenesis genes using quantitative real-time PCR. Statistical comparisons, correlation matrices, and ROC analyses were performed to characterize gene-expression differences. These results were integrated with multigene logistic modeling, decision-curve analysis, and exploratory random forest/SHAP approaches to evaluate molecular interactions and diagnostic relevance. Results: DROSHA, DICER1, and TARBP2 were significantly downregulated in both MDS and AML, suggesting impaired miRNA maturation and a loss of global post-transcriptional control. DGCR8 expression increased across higher-risk MDS groups, suggesting compensatory activation of the Microprocessor complex, whereas AGO1 levels remained relatively stable, consistent with partial maintenance of RISC function. Correlation analyses revealed a co-regulated DROSHA–TARBP2–AGO1 module. ROC, logistic, and machine learning models identified DGCR8 and DICER1 as the strongest diagnostic discriminators. The integrated five-gene signature achieved high discriminative performance (AUC ≈ 0.98) and showed promise but remains preliminary potential for clinical application. Conclusions: Our findings suggest that defects in miRNA biogenesis disrupt hematopoietic homeostasis, reflecting common mechanisms in MDS and AML. The dysregulation of DICER1, DGCR8, and TARBP2 offers insights into miRNA-driven leukemogenesis and may pave the way for miRNA-based diagnostic and therapeutic strategies, pending validation in larger cohorts. Although transcript-level data are provided, future studies should include functional validation to determine the impact on downstream miRNA processing and hematopoietic pathways.

  İncele
• MakaleAçık Erişim2023Scopus SJRQ1/r/bayburt/13155
  Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain

  Turan Yücel, Nazlı; Kandemir, Ümmühan; Üçel, Umut İrfan; Demir Özkay, Ümide; Can, Özgür Devrim

  The therapeutic potential of vortioxetine on mechanical hyperalgesia/allodynia was investigated in rats with streptozotocin-induced diabetes, and its possible mechanism of action was elucidated in this study. The obtained findings demonstrated that subacute vortioxetine treatment (5 and 10 mg/kg for 2 weeks) increased the reduced paw-withdrawal thresholds of diabetic rats both in the Randall–Selitto and Dynamic plantar tests. Moreover, the falling latencies of animals did not change in the Rota-rod assessments. These results suggest that vortioxetine administration significantly improved diabetes-induced hyperalgesia and allodynia responses in the rats without affecting their motor coordination. The vortioxetine (5 mg/kg)-induced antihyperalgesic and antiallodynic effects were reversed by AMPT, yohimbine, ICI 118,551, sulpiride and atropine pre-treatments, suggesting the involvement of the catecholaminergic system, α2- and β2-adrenoceptors, D2/3 dopaminergic receptors and cholinergic muscarinic receptors in the exhibited pharmacological activity, respectively. Moreover, the data from the immunohistochemical studies indicated that the inhibition of c-Fos overexpression in dorsal horn neurons also mediates the beneficial effect of this drug. Vortioxetine induced no difference in plasma glucose levels in diabetic rats. If clinical studies confirm these findings, the concomitant beneficial effect of vortioxetine on mood disorders and its neutral activity profile on glycemic control may make it an alternative drug for the treatment of neuropathic pain.

  • 
  AtıfScopus6·WoS4·OpenAlex6

  İncele