Tohoku Journal of Experimental Medicine最新文献

Circular RNA DLGAP4 (circ_DLGAP4) participates in the progression of ischemic stroke (IS), but whether it could regulate microglia activation to affect IS injury is unclear. This study aimed to explore the effect of circ_DLGAP4 on IS-induced microglia polarization and inflammatory cytokines, and the underlying mechanism. BV-2 cells (microglia) were transfected with circ_DLGAP4 overexpression (oeCirc), short hairpin RNA plasmid (shCirc), or corresponding negative control plasmids (oeNC and shNC). oeCirc or oeNC transfected cells were also treated with phorbol 12-myristate 13-acetate (PMA). Subsequently, BV-2 cells were treated with oxygen-glucose deprivation and reperfusion (OGD/R) to mimic IS. Circ_DLGAP4 was reduced in OGD/R-stimulated microglia versus normal microglia. Circ_DLGAP4 overexpression decreased cluster of differentiation (CD)68 and CD86, but increased CD206 and arginase-1 in OGD/R-stimulated microglia, suggesting that circ_DLGAP4 overexpression might inhibit M1 but facilitate M2 polarization of microglia. Besides, circ_DLGAP4 overexpression reduced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, but elevated IL-10 in OGD/R-stimulated microglia, indicating that circ_DLGAP4 overexpression reduced proinflammatory cytokines but facilitated anti-inflammatory cytokines. Circ_DLGAP4 overexpression decreased p-nuclear factor kappa-B (NF-κB) and p-NF-κB inhibitor (IκB)-α in OGD/R-stimulated microglia, suggesting its inhibition of the NF-κB pathway. Notably, circ_DLGAP4 downregulation reversed the above phenomenon. PMA facilitated M1 polarization and proinflammatory cytokines but inhibited M2 polarization and anti-inflammatory cytokines in OGD/R-stimulated microglia. Interestingly, PMA attenuated the effect of circ_DLGAP4 overexpression on the above-mentioned processes in OGD/R-stimulated microglia. In conclusion, circ_DLGAP4 may attenuate IS injury by inhibiting microglia M1 polarization and proinflammatory cytokine production, which may be attributed to the inactivation of the NF-κB pathway.

Myeloproliferative disorders (MPDs) are rare diseases in which the bone marrow produces too many red, white, or platelets. Myeloproliferative disorders are neither acute nor leukaemia. To study ruxolitinib's effect on MPD therapy and CD4⁺ T cell expression. In total, 66 JAK2V617F-positive MPD patients were admitted to our hospital. The patients were randomly assigned to control and research groups (each 33). Hydroxyurea pills were given to the control group and ruxolitinib to the observation group. The MPN-10 assesses 10 of the most clinically relevant symptoms, including fatigue and generates a Total Symptom Score (TSS). In addition, by comparing myelofibrosis (MF), spleen length, JAK2V617F gene expression, peripheral blood lymphocyte and T cell levels, and prognostic levels, analyze the shortcomings of each group. Post-treatment, MPN-10, MF, and spleen length diameter were reduced in both groups (P < 0.05), with the study group showing a higher reduction than the control group (P < 0.05). Compared to prior treatment, JAK2V617F gene expression was reduced in all groups after 6 months and a year of medication. The study category had a higher decrease in expression than the control group. After therapy, CD4 and CD4/CD8 levels rose, but CD8 and Treg levels decreased. The study group had increased CD4 and CD4/CD8 levels, whereas the control group had lower CD8 and Treg levels . The study group had a greater 1-year survival rate than the control group, but the control group had lower mortality and adverse event rates. In JAK2V617F-positive MPD patients, ruxolitinib reduces JAK2V617F gene expression, myelofibrosis, and therapeutic impact.