INTRODUCTION: Objectives: The purpose of this study is to investigate the effect of Olea europaea leaf extract (OLE) on senescence and senescence-associated secretory phenotype (SASP) caused by temozolomide (TMZ) in Glioblastoma (GB).


METHODS: Materials and Methods: A Senescence β-Galactosidase assay and a colony formation assay were used to determine the effects of OLE, TMZ, and OLE+TMZ on cellular senescence and aggressiveness of GB cell lines T98G and U87MG. mRNA expression levels of P53, a senescence factor, IL-6, MMP-9, and NF-κB1 as SASP factors and Bcl-2 and Bax as senolytic markers were assessed using RT-qPCR. Cells were double-stained with Acridine Orange (AO) and Propidium Iodide (PI) to observe the cell morphology.

RESULTS: Results: TMZ increased the senescence rate of GB cells (p<0.001). Besides, OLE+TMZ reduced the proportion of senescent cells (p<0.001) and their capability to form colonies compared to TMZ-only treated cells. In addition, OLE+TMZ co-treatment elevated the mRNA expression levels of MMP-9, IL-6, NF-κB1, p53, and the Bax/Bcl-2 ratio compared to TMZ-only treatment. Especially in U87MG cells, involvement of OLE in TMZ treatments led to an increase of more than six times in the Bax/Bcl-2 ratio compared to TMZ-only, which resulted in the induction of the apoptosis-like morphological features (p<0.0001).

DISCUSSION AND CONCLUSION: Conclusion: Collectively, our findings showed the inhibitory effect of OLE on TMZ mediated SASP-factor production in GB and, accordingly, its potential contribution to elongate the time of recurrence.

INTRODUCTION: Rutin has been broadly applied in the treatment of several diseases due to its pharmacological activities. However, its low aqueous solubility limits its absorption and bioavailability. The aim of this research is to increase the solubility of rutin using cyclodextrin and to develop a temperature-triggered in situ gelling system for dermal application.
METHODS: The solubility of Rutin was increased with SBE-β-CD. Rutin- SBE-β-CD inclusion complex was prepared by kneading and freeze dying method. Structural characterization was carried out using DSC and FTIR. İn situ gel formulations were prepared with Pluronic F127 (PF127), a thermosensitive polymer, and Chitosan (CH),a natural, biodegradable and mucoadhesive hydrophilic polymer. In situ gel characteristics like pH, clarity, gelation temperature and viscosity were determined.
RESULTS: When the solubility diagrams were examined, it was concluded that SBE-β CD showed a linear increase, therefore AL-type diagram was selected. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. Three in situ gels were evaluated for their pH, gelling temperature and the rheological behaviors and one formulation was selected. It was observed that the formulations had a pH between 6-6,1, and their gelation temperature decreased with increasing PF127 which were between 20 °C to 34 °C. For the selected formulation(Formulation E3 ) 0.5% Rutin and Rutin/ SBE-β-CD were transfered to in situ gelling system. As a result of in vitro release studies, it was observed that the release of the Rutin/SBE-β-CD inclusion complex containing NZ formulation showed a higher burst effect than the others and the release continued for 6 hours.
DISCUSSION AND CONCLUSION: The results indicated that the combination of PF127 and CH can be a hopeful in situ gelling vehicle for dermal delivery of Rutin and Rutin/ SBE-β-CD.

INTRODUCTION: The objective of this study was to develop a Turkish scale to assess medication literacy and evaluate its psychometric properties among adults having at least 12 years of education in Turkey.
METHODS: After the composition of a preliminary set of items, the content validity of the scale was assessed by an e-Delphi process and a pilot study. The psychometric properties of the scale were evaluated in 358 participants who had above 12 years of education; university students, academic and administrative staff from two faculties (pharmacy, law) in two universities (Marmara University and Ankara University) located in two different cities (Istanbul and Ankara) in Turkey between March 2021 and May 2021. The test-retest validity was assessed by Spearman’s rho and Wilcoxon test). Internal consistency was evaluated by Kuder Richardson 20. Principal component analysis was conducted.
RESULTS: The last version of the medication literacy scale consisted of 8 items. There was a positive correlation (Spearman’s rho=0.570; p<0.01) and no significant difference (p=0.308) between the scores of the scale at baseline and after a two-week interval. Kuder Richardson 20 coefficient was 0.659. Students and graduates of health sciences had significantly higher scores on the medication literacy scale when compared to participants who did not have any education in health sciences (the median [25th-75th percentiles]: 8.0 [8.0-8.0] vs 7.0 [6.0-8.0], respectively; p<0.001).
DISCUSSION AND CONCLUSION: The Turkish version of MEdication Literacy Scale for Adults (MELSA-TR) is a valid tool to evaluate medication literacy among adults who have above 12 years of education in Turkey. Still the generalizability of our findings should be evaluated with caution since this study was conducted in a sample with a significant representation from healthcare professionals. It would be useful to conduct further studies evaluating the psychometric properties of this scale in participants with diverse characteristics.

INTRODUCTION: Early detection of bone cancer is critical for treating symptoms, minimizing pain, and increasing overall quality of life. It is critical to develop novel radiopharmaceuticals with high labeling efficiency and stability for the diagnosis of bone cancer. The goal of this research is to design a novel radiopharmaceutical that may be utilized to diagnose bone cancer.
METHODS: In this study, ibandronate sodium (IBD), a bisphosphonate analogue, was radiolabeled with technetium-99m (99mTc) and quality control tests of the newly developed radiopharmaceutical ([99mTc]Tc-IBD) were done using radioactive thin layer chromatography (RTLC). After that, the incorporation of [99mTc]Tc-IBD into hydroxyapatite crystals and a human bone osteosarcoma cell line (U2OS) was tested.
RESULTS: According to the results obtained, optimal radiolabeling procedure was obtained for [99mTc]Tc-IBD with 200 µg.mL-1 IBD, 20 µg stannous chloride and 99mTc with 37 MBq radioactivity. The reaction mixture was adjusted to pH 5.5 and incubated at room temperature for 15 min. The radiochemical purity of [99mTc]Tc-IBD was found to be greater than 95% at room temperature for up to 6 h. In addition, chromatography analysis showed >95% [99mTc]Tc-IBD complex formation with promising stability for up to 24 h in saline and up to 2 h in cell medium. The percent binding of IBD to hydroxyapatite was 83.70±3.67 and the logP of [99mTc]Tc-IBD was -1.1014. The radiolabeled complex showed a higher rate of cell incorporation to U2OS cells compared to Reduced/Hydrolyzed 99mTcO4-.
DISCUSSION AND CONCLUSION: The newly produced radiopharmaceutical is very promising, according to the results of in vitro cell culture, hydroxyapatite binding, and quality studies, and will be a step forward for further studies in nuclear medicine for bone cancer diagnostics.

INTRODUCTION: The study’s aim was to evaluate stress-protective effect of oligopeptides-homologues of the ACTH fragment 15-18 on morphogenetic signs of stress reaction of the adrenal glands under acute cold exposure in rats.
METHODS: The acute cold stress was reproduced by placing random-bred male rats in a freezer at a temperature of -18 ° C for 2 hours. The peptides-homologous of the ACTH15-18 Acetyl-(D-Lys)-Lys-Arg-Arg-amide (KK-1) and Acetyl-(D-Lys)-Lys-(D-Arg)-Arg-amide (KK-5) and the reference medicine Semax were administered intranasally in a dose of 20 mcg/kg 30 minutes before and after cold exposure. Rectal temperature was measured before and 10 minutes after cold exposure. Zona glomeruloza, zona fasciculata, zona reticularis, and the area of cells and nuclei of adrenocorticocytes of zona fasciculate were measured.
RESULTS: KK-1 significantly prevented structural changes in the adrenal cortex and medulla, stabilized the secretory activity of glucocorticoid-producing cells. However, the congestion of capillaries of zona fasciculata and zona reticularis remained in some locations. Zona fasciculata cells had a marked tendency to decrease, and the area of nuclei significantly decreased (p<0.05) recovering the width to control animals' markers. KK-5 had more marked recovery of the adrenal glands (a greater saturation of cytoplasm of adrenocorticocytes of zona glomerulosa and zona fasciculate). The number of chromaffin cells at rest was increased in the adrenal medulla. KK-5 statistically significantly normalized both the area of cells (p<0.05) and the area of nuclei (p<0.05) of zona fasciculata, unlike KK-1, which reliably restored only the marker of the nuclei area. Some morphometric parameters of acute stress hypertrophy remained in the adrenal glands of rats receiving Semax.
DISCUSSION AND CONCLUSION: KK-1 and KK-5 prevented the manifestation of acute stress reactions in the adrenal cortex of rats. KK-5 had a more marked stress-protective effect compared to the peptide KK-1. Both studied substances exceeded the reference medicine Semax. KK-5 is a promising stressprotector and frigoprotector.

INTRODUCTION: Mefenamic acid (MA) is a strong nonsteroidal anti-inflammatory drug (NSAID), but because of its limited oral bioavailability and the side effects that come with taking it systemically, it is better to apply it topically. The major goal of this study was to see how certain permeation enhancers affected mefenamic acid's in vitro skin permeability. In manufactured Franz diffusion cells, mefenamic acid permeability tests using rat skin pretreatment with several permeation enhancers such as corn oil, olive oil, clove oil, eucalyptus oil, and menthol were conducted and compared to hydrate rat skin as a control.
METHODS: The steady-state flux (Jss), permeability coefficient (Kp), and diffusion coefficient are among the permeability metrics studied. The permeability enhancement mechanisms of the penetration enhancer were investigated using Fourier transform infrared spectroscopy (FTIR) to compare changes in peak position and intensities of asymmetric (Asy) and symmetric (Sym) C-H stretching, C=O stretching, C=O stretching (Amide I), and C-N stretching of keratin (Amide II) absorbance, as well as differential scanning calorimetry (DSC) to compare mean transition temperature (Tm) and their enthalpies (H).
RESULTS: Clove oil, olive oil, and Eucalyptus oil were the most effective enhancers, increasing flux by 7.91, 3.32, and 2.6 times, as well as diffusion coefficient by 3.25, 1.34, and 1.25, respectively, when compared to moist skin. FTIR and DSC data show that permeation enhancers caused lipid fluidization, extraction, disruption of lipid structures in the SC layer of skin, and long-term dehydration of proteins in this area of the skin.
DISCUSSION AND CONCLUSION: According to the findings, the permeation enhancers utilized improved drug permeability through excised rat skin. The most plausible mechanisms for greater ERflux, ERD, and ERP ratios were lipid fluidization, disruption of lipid structure, and intracellular keratin irreversible denaturation in the stratum corneum by eucalyptus oil, menthol, corn oil, olive oil, and clove oil.

INTRODUCTION: Dexketoprofen is a non-steroidal analgesic/anti-inflammatory drug and its’ trometamol salt is extensively preferred in mild or moderate pain due to its rapid onset of relief. A new formulation of 36.9 mg of dexketoprofen trometamol (equivalent to 25 mg of dexketoprofen) tablet has been developed and its bioequivalence to the reference product was proven.
METHODS: An open-label, single-dose, randomized, two-period, cross-over bioequivalence study was conducted with healthy males under fasting conditions for two different tablet formulations of 25 mg of dexketoprofen. In order to prove the bioequivalence of the test product with the reference product, the comparison study has been performed in compliance with regulations in force under Good Clinical Practice principles. A single-center clinical study was run and blood samples of the participants have been withdrawn at specified time points, before and after dosing, to measure the plasma concentrations of dexketoprofen trometamol. A validated analytical method has been developed by using an LC-MS/MS instrument to assess the plasma concentrations of the test and reference products.
RESULTS: 47 volunteers completed the clinical phase of the study. For the test and reference products, the mean ± SD of Cmax were found 2543.82 ± 655.42 ng/mL and 2539.11 ± 662.57 ng/mL, and the mean ± SD of AUC0-tlast were found 3483.49 ± 574.42 h.ng/mL and 3560.75 ± 661.83 h.ng/mL, respectively. The primary target variables data demonstrate the bioequivalence of test and reference products with regard to 90% CI for Cmax of 92.45 – 108.53 and for AUC0-tlast of 95.57 – 100.87. The geometric mean ratios were found as 100.16% and 98.18% for Cmax and AUC0-tlast, respectively. There were no serious adverse events or adverse reactions reported throughout the study.
DISCUSSION AND CONCLUSION: After statistical evaluation of the analytical results, the test and reference products were considered to be bioequivalent. Both products were well tolerated and considered as safe.

The recently explained cytokine which is produced after the stimulation of IFN-c, IL-2 and IL-18 is Interleukin-32 (IL-32). This cytokine has proinflammatory IFN-c, IL-2 and IL-18 are Interleukin-32 (IL-32) mediator's properties that are generally entailed in many diseases, including infections, cancer and chronic inflammation. After the initial statement in 2005, it promoted the osteoclast precursor’s differentiation into TRAcP plus VNR plus multinucleated cells which express explicit osteoclast indicators. Furthermore, the loss of bone resorption might be accredited because of the collapse of the multinucleated cells which are produced of the reaction to IL-32 to direct Factoring that is ultimately essential for the attachment of the cells for bone resorption. Thus, in conclusion, the proinflammatory mediator interleukin-32 has important and indirect role to regulate the osteoclast differentiation. In bone disorder’s pathophysiology, the critical role of IL-32 needs more scientific evidences to develop a rational treatment protocol. IL-32 can become a potent mediator of active osteoclast generation in the presence of RANKL. This novel cytokine can introduce more favorable conditions for osteoclastogenesis in the rheumatic arthritis by increasing the RANKL and Osteoprotegerin ratio in fibroblast-like synoviocytes.