Sirtuins are involved in the fate of hematopoietic stem cells (HSCs), including their metabolism, stress response, differentiation, migration, and apoptosis. The aim of this study was to explore SIRT1-7 expression during HSC mobilization. The study included 50 patients with lymphoproliferative disorders (39 multiple myeloma, 11 lymphoma). Samples were taken before mobilization (day 0) and on the day of first apheresis (day A). The sirtuin expression was evaluated by the Droplet Digital PCR (ddPCR) method. A significant increase of the SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 levels measured at day A as compared to baseline was observed. The study revealed a positive correlation between SIRT5, SIRT6, and SIRT7 expression and the CD34+ peak value in peripheral blood and the number of CD34+ cells collected on day A. Patients from the SIRT7 “high expressors” group collected more CD34+ cells on day A than “low expressors”. Upregulated expressions of SIRT3 and SIRT7 on the day of first apheresis were observed in patients in complete remission status (CR) as compared to the non-CR group. Our results suggest that the investigated sirtuins may influence the HSC migration and hematopoietic landscape during mobilization. SIRT5, SIRT6, and SIRT7 may be associated with the efficacy of HSC mobilization.

Glioblastoma, a highly aggressive brain tumor, poses significant treatment challenges. A deeper investigation into its molecular complexity is essential for the identification of novel prognostic biomarkers and therapeutic strategies, potentially improving patient outcomes in terms of survival and quality of life. While nuclear DNA mutations have been extensively studied, the role of mitochondrial DNA (mtDNA) mutations, specifically in the D-loop region, remains poorly understood. This prospective case-control study aimed to assess the prognostic significance of the mtDNA D-loop m.16126T>C variant in glioblastoma patients. Immunohistochemistry and droplet digital PCR (ddPCR) were employed for mutation analysis, complemented by statistical analyses and a literature review. The study cohort comprised 22 glioblastoma patients (mean age 59.36 ± 14.17, 12 (54.55%) females), and 25 controls (59.48 ± 13.22, 12 (80%) females). The D-loop m.16126T>C variant was observed in four (18%) of the glioblastoma samples and was associated with shorter median survival (9.5 vs. 18 months; p = 0.016, log-rank test). This study underscores the importance of investigating mtDNA, especially D-loop variants, in glioblastoma, suggesting its potential as a prognostic biomarker and, therefore, its possible therapeutic targets, warranting further exploration.

The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.

CD4+ T cells are considered the main orchestrators of autoimmune diseases. Their disruptive effect on CD4+ T cell differentiation and the imbalance between T helper cell populations can be most accurately determined using experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). One epigenetic factor known to promote autoimmune inflammation is miRNA-155 (miR-155), which is significantly upregulated in inflammatory T cells. The aim of the present study was to profile the transcriptome of immunized mice and determine their gene expression levels based on mRNA and miRNA sequencing. No statistically significant differences in miRNA profile were observed; however, substantial changes in gene expression between miRNA-155 knockout (KO) mice and WT were noted. In miR-155 KO mice, mRNA expression in CD4+ T cells changed in response to immunization with the myeloid antigen MOG_35-55. After restimulation with MOG_35-55, increased Ffar1 (free fatty acid receptor 1) and Scg2 (secretogranin-2) expression were noted in the CD4+ T cells of miR-155-deficient mice; this is an example of an alternative response to antigen stimulation.

Delirium is a neuropsychiatric syndrome that is pathophysiologically related to both mental (dementia, depression) and physical illness. Its occurrence results in a poor prognosis. This study investigates whether specific miRNAs (miR-9-3p, miR-34c-5p, miR-96-5p, miR-183-5p, and miR-374-3p) related to brain function are associated with an increased risk of postoperative delirium. A total of 224 adult individuals scheduled for elective cardiac surgery were eligible to participate in the study. Delirium diagnosis was established with the use of the Confusion Assessment Method. Following miRNA expression profiling, cDNA synthesis was conducted on the samples obtained one day before and the day after surgery, from 60 delirium patients and 60 randomly selected non-delirium individuals. Univariate comparisons revealed that preoperative miR-96-5p (p = 0.05) and miR-183-5p (p = 0.001), along with postoperative miR-34c-5p (p = 0.009), miR-96-5p (p = 0.07), and miR-183-5p (p = 0.05), were associated with the risk of post-surgery delirium. However, after conducting multivariate logistic regression analysis, only miR-183-5p was found to be independently associated with the risk of delirium development. Other predictors of delirium included an ongoing episode of depression, peripheral vascular disease, female gender, active smoking, and increased postoperative pCO2 concentration. The current study revealed that preoperatively decreased expression of miR-183-5p predicts delirium development after cardiac surgery.

Background: Delirium is a neuropsychiatric syndrome that is pathophysiologically related to both mental (dementia, depression) and physical illness. Its occurrence results in a poor prognosis. Specific miRNAs play a role in regulating central nervous system development, neuroinflammation, and neurodegeneration. This study investigates whether specific miRNAs (miR-9-3p, miR-34c-5p, miR-96-5p, miR-183-5p, and miR-374-3p) related to brain function are associated with an increased risk of postoperative delirium. Methods: A total of 224 adult individuals scheduled for elective cardiac surgery were eligible to participate in the study. Prior to surgery, each patient underwent psychiatric evaluation to identify major depressive disorder based on the DSM-5 criteria. Delirium diagnosis was established with the use of the Confusion Assessment Method. Following miRNA expression profiling, cDNA synthesis was conducted on 60 delirium patients and 60 randomly selected non-delirium individuals. MiRNA dqPCR analysis was performed on the serum samples obtained one day before and the day after surgery. Results: Of the 177 patients finally included, 34% (61 cases) experienced delirium. Univariate comparisons revealed that preoperative miR-96-5p (p=0.05) and miR-183-5p (p=0.001), along with postoperative miR-34c-5p (p=0.009), miR-96-5p (p=0.07), and miR-183-5p (p=0.05), were associated with the risk of post-surgery delirium. However, after conducting multivariate logistic regression analysis, only miR-183-5p was found to be independently associated with the risk of delirium development. Other predictors of delirium included an ongoing episode of depression, peripheral vascular disease, female gender, active smoking, and increased postoperative pCO2 concentration. Conclusion: The current study revealed that preoperatively decreased expression of miR-183-5p predicts delirium development after cardiac surgery.