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Background The therapeutic potential of mesenchymal stem cells (MSCs)-derived conditioned media (CM) can be increased after preconditioning with various chemical agents. The aim of this study is comparative evaluation of effects of N-CM and DFS-CM which are collected from normal (N) and deferoxamine (DFS) preconditioned umbilical cord-derived MSCs on rat diabetic nephropathy (DN) model. Methods After incubation of the MSCs in serum-free medium with/without 150 µM DFS for 48 h, the contents of N-CM and DFS-CM were analyzed by enzyme-linked immunosorbent assay. Diabetes (D) was induced by single dose of 55 mg/kg streptozotocin. Therapeutic effects of CMs were evaluated by biochemical, physical, histopathological and immunohistochemical analysis. Results The concentrations of vascular endothelial growth factor alpha, nerve growth factor and glial-derived neurotrophic factor in DFS-CM increased, while one of brain-derived neurotrophic factor decreased in comparison with N-CM. The creatinine clearance rate increased significantly in both treatment groups, while the improvement in albumin/creatinine ratio and renal mass index values were only significant for D + DFS-CM group. Light and electron microscopic deteriorations and loss of podocytes-specific nephrin and Wilms tumor-1 (WT-1) expressions were significantly restored in both treatment groups. Tubular beclin-1 expression was significantly increased for DN group, but it decreased in both treatment groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cell death increased in the tubules of D group, while it was only significantly decreased for D + DFS-CM group. Conclusions DFS-CM can be more effective in the treatment of DN by reducing podocyte damage and tubular apoptotic cell death and regulating autophagic activity with its more concentrated secretome content than N-CM. Graphical Abstract

Aim: To our knowledge; this is the first study that compared the efficacy and safety of aripiprazole 1-month and paliperidone 1-month and paliperidone 3-month long-acting forms preparations as well as plasma drug levels during the maintenance treatment of schizophrenia in the real world. Method: In our study, subjects were evaluated every month for four months with relevant psychiatric measures and plasma drug levels. Follow-up days were determined as days 0, 30, 60, and 90. Plasma drug levels of the treatments were analyzed by using LC/MS-MS. Results: No superiority was observed between the groups regarding PANSS positive and general psychopathology (p>0.05). It was observed that PANSS negative and total scores were statistically lower in the aripiprazole once-monthly group than in the paliperidone 3-month preparations (p<0.05). We observed that Quality of Life Scale interpersonal relations scores, the aripiprazole 1-month group exhibited higher scores than both of the paliperidone groups. Aripiprazole 1-month group scored higher than the paliperidone 1-month group in the intrapsychic foundations subscale (p<0.05). No significant difference was observed between extrapyramidal adverse effect, akathisia, and insight levels among the three groups (p>0.05). Aripiprazole 1- month group scored significantly lower than both paliperidone groups in the Arizona Sexual Experiences Scale (p<0.001). Aripiprazole metabolite was negatively correlated with depressive symptoms in the Calgary Depression Assessment Scale in Schizophrenia (p<0.05) and the Barnes Akathisia Rating Scale (p<0.05). Conclusion: Aripiprazole once-monthly showed superiority in efficacy aspects to PP3M but not PP1M and similar safety with both paliperidone formulations.

Aim: Losartan, a drug in the angiotensin receptor blocker (ARB) family, is the substrate of the Multi Drug Resistance-1 (MDR1) drug-efflux protein encoded by the ABCB1 gene. This study seeks to investigate the MDR1 gene polymorphism and losartan concentration in order to identify drug resistance in patients presenting to the emergency department (ED) with a hypertensive episode while having losartan treatment. Method: The patient cohort was comprised of 50 individuals presenting with a hypertensive episode while under losartan treatment. The control cohort included 50 patients whose blood pressure was regulated while receiving losartan treatment and who were admitted to the ED for reasons other than hypertensive episode. Allele-specific PCR analysis was carried out in order to determine the frequencies of the G2677T/A, C3435T and C1236T genotypes. Plasma losartan and EXP3174 levels of the patients were calculated using tandem mass spectrometry Findings: The frequencies of GG, GT, GA, TA and TT genotypes did not differ significantly between the cohorts in G2677T/A single nucleotide polymorphism (SNP) (p>0.05), whereas those of C3435T TT and C1236T CT genotypes yielded a significant difference between the patient and control cohorts (p<0.05). Besides, no significant difference was evident between G2677T/A, C3435T and C1236T genotypes with respect to plasma losartan/EXP3174 concentration (p>0.05). Conclusion: We provided clinical evidence that hypertensive episodes occurred more frequently in C3435T TT and less frequently in C1236T CT. However, no significant correlation was established between plasma losartan, EXP3174 concentration and G2677T/A, C3435T, and C1236T genotypes. Keywords: Losartan, MDR1, Genetic polymorphism, EXP3174, Hypertension