Poznan University of Medical Sciences

Glioblastoma, a primary brain tumor of the CNS, is the most malignant lesion among gliomas. It has a median survival time of about 12-15 months after diagnosis and limited treatment options. That neoplastic processes result from changes in the cell's redox potential and the overproduction of reactive oxygen species. As a consequence, the epigenetic marker, m5C of DNA, is oxidized with ROS to 5-hydroxymethylcytosine, but guanosine is damaged to 8-oxo-dG, a general probe of oxidative stress. If so, the m5C, as well as 8-oxo-dG content in DNA, are subject to dynamic changes induced by environmental and endogenous cellular factors. These markers can be used to evaluate new therapeutic agents, among others. Currently, there are no effective drugs against human glioblastoma. Cannabinoids, small, lipophilic molecular compounds, are increasingly being studied for their antitumor properties. Using the precise nucleotide post-labelling method and thin-layer chromatographic analysis we monitored the effect of CBD, THC, and CFE, as well as their combination with temozolomide, on changes of global m5C and 8-oxo-dG contents. These results show that cannabinoids alone or in combination with the current standard glioblastoma chemotherapeutic, TMZ, inhibit the progression of GBM and could be used for its clinical treatment. The mechanism of cannabinoids' actions on glioblastoma cells is also proposed.

Our study aimed to evaluate the performance and concordance of parathyroid hormone wash-out (PTHw) and 99mTc-MIBI+SPECT/CT (MIBI) in preoperative localization for patients with primary hyperparathyroidism (PHPT), and assess potential factors influencing their diagnostic utility including patient characteristics, lesion size and comorbidities. This was a real-life, retrospective study involving 125 participants, who underwent ultrasound-guided fine needle aspiration biopsy with PTHw determined by electrochemiluminescence (Elecsys analyser) and subtraction scintigraphy together with SPECT/CT images. PTHw was positive in 84.8

Although therapeutic drug monitoring (TDM) is recommended for personalized clozapine (CLO) dose titration, there are no widely accepted international guidelines regarding routine TDM during long-term outpatient CLO treatment and many clinicians have limited access to TDM. This retrospective, naturalistic study aimed to examine whether CLO and norclozapine (NCLO) concentrations measured only at the time of inpatient care could predict the risk of psychiatric rehospitalization after discharge, irrespective of the potential influence of confounding factors on long-term outcomes. A total of 141 blood samples from psychiatric inpatients (71 females and 70 males, aged from 18 to 74 years) were analyzed. Serum CLO and NCLO levels were determined with high-performance liquid chromatography coupled with a UV detector. We assessed the rates of rehospitalization over 360 days after discharge. There was no correlation between either CLO or NCLO concentrations and psychiatric rehospitalization rates at any follow-up time points (day 90, 180, or 360). However, patients receiving CLO as a single psychotropic drug had significantly fewer rehospitalizations (assessed at 180 and 360 days of follow-up, p < 0.001) occurred among patients receiving CLO as a single psychotropic drug compared to combination therapy. The risk of rehospitalization was also higher in patients with a greater number of previous hospitalizations (OR = 1.15, p = 0.002) and in those taking additional psychotropic drugs (OR = 1.51, p = 0.010). Our naturalistic retrospective study (based on an in-hospital TDM database) showed no association between the baseline steady-state CLO and NCLO levels established during hospitalization and the risk of psychiatric rehospitalization. However, the use of CLO in combination with other psychotropic drugs and the number of previous hospitalizations correlated with the risk of rehospitalization. Not applicable.

Inosine pranobex (IP) is a long-used antiviral drug whose mechanism of action remains incompletely understood. However, molecular efficacy has been attributed mainly to immunomodulatory effects. There are data which suggest that the cellular activity of IP stems from its major constituent compound, inosine, known for its pleiotropic roles in purine metabolism, RNA modification, and translation regulation. We investigated whether IP acts as a stable complex or a mixture of its components and compared the biological effects of inosine itself and IP in vitro. The structural composition of IP was analyzed using compositional and microscopic methods. Cytotoxicity, antiviral activity against coxsackievirus B3 (CVB-3), and global DNA methylation changes were evaluated in A549 and HeLa cell lines using MTT, colony formation, plaque reduction, and post-labeling methods, respectively. We found that IP is physically heterogeneous and function as a mixture of components rather than a stable complex. In cell-based assays, inosine exhibited higher antiviral activity than IP, particularly under pre-treatment conditions, where it provided stronger protection against CVB-3-induced cytopathic effects. Neither compound showed significant cytotoxicity within the tested concentration ranges. Both inosine and IP influenced global DNA methylation levels, but inosine induced more pronounced and concentration-dependent changes. The superior antiviral and epigenetic activity of inosine compared with IP suggests that inosine is the main principal active component responsible for IP's biological effects. While IP's immunomodulatory functions were not evaluated here, our findings strongly suggest that inosine contributes substantially to its antiviral efficacy. Further studies, including in vivo models, are warranted to clarify the epigenetic mechanism underlying these observations.

Bronchopulmonary dysplasia (BPD) – also termed chronic lung disease of prematurity – remains a principal cause of death and long-term morbidity in very preterm infants. Azithromycin is active against Ureaplasma and has both antibacterial and anti-inflammatory properties, making it a plausible preventive therapy. Evidence, however, is inconclusive. We evaluated whether azithromycin improves survival free of moderate or severe, physiologically defined chronic lung disease in this high-risk population. Following the Cochrane Handbook, we conducted a systematic review and meta-analysis and reported according to PRISMA (PROSPERO CRD42024589280). We searched PubMed, SCOPUS, Web of Science, EMBASE, and CENTRAL from inception to April 2024. Dichotomous outcomes were pooled as risk ratios (RRs), and continuous outcomes were pooled as mean differences (MDs) using RevMan 5.4; P < 0.05 denoted statistical significance. Seven double-blind randomized controlled trials involving 1,481 infants (azithromycin, n = 740; placebo, n = 741) met the inclusion criteria. Azithromycin did not significantly reduce any primary outcome: BPD (RR, 0.97; 95