Bleomycin-induced trans lipid formation in cell membranes and in liposome models

Cell cultures of NTera-2 cells incubated with bleomycin and liposomes as biomimetic models of cell membranes were used for examining some novel aspects of drug-metal induced reactivity with unsaturated lipids under oxidative conditions. In cell cultures, bleomycin was found for the first time to cause the formation of trans fatty acids. The chemical basis of this transformation was ascertained by liposome experiments, using bleomycin-iron complexes in the presence of thiol as a reducing agent that by incubation at 37 °C gave rise to the thiyl radical-catalysed double bond isomerisation of membrane phospholipids. The effect of oxygen and reagent concentrations on the reaction outcome was studied. An interesting scenario of free radical reactivity is proposed, which can be relevant for understanding the role of membrane lipids in antitumoral treatments and drug carrier interaction.Fil: Cort, Aysegul. Akdeniz University. Faculty of Medicine; Turquía. Consiglio Nazionale delle Ricerche; ItaliaFil: Ozben, Tomris. Akdeniz University. Faculty of Medicine; TurquíaFil: Sansone, Anna. Consiglio Nazionale delle Ricerche; ItaliaFil: Barata Vallejo, Sebastian. Consiglio Nazionale delle Ricerche; Italia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chatgilialoglu, Chryssostomos. Demokritos National Centre For Scientific Research; GreciaFil: Ferreri, Carla. Consiglio Nazionale delle Ricerche; Itali

Effects of laparoscopic sleeve gastrectomy on serum lncRNA levels in obese patients

Obesity is a disease associated with excessive fat accumulation in the body, which body mass index (BMI) is greater than 30 kg/m. Bariatric surgery technique is one of the most common treatment options for obesity with the advantage of faster weight loss in a short time. lncRNAs play a role in adipogenesis and metabolic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), osteoarthritis, and hypertension, so they are significant targets for therapeutic options. In this study, we aimed to determine lncRNAs and specific parameters that show different expressions in the plasma of patients with obesity. We included fifteen patients with BMI greater than 30 kg/m2 before and less than 30 kg/m2 after laparoscopic sleeve gastrectomy (LSG) in the study. Total RNAs, including lncRNAs and other non-coding RNAs, were isolated from plasma samples of patients, and eight lncRNAs (H19, Neat1, HOTAIR, ANRIL,  MALAT1, ATB, SNGH5, UCA1) were quantified by real-time PCR. Gene Ontology, KEGG, and relation of obesity analysis were utilized. Unpaired Student's t-test Pearson correlation analysis was used for statistical analysis. We observed a statistically significant increase in the expression levels of all lncRNAs in the patients with the post-operative BMI change. We have added a new dimension to the biomarker studies related to obesity and the clinical follow-up of patients undergoing LSG surgery. Further studies are required for enlighting the molecular mechanisms

Verbascoside potentiates the effect of tyrosine kinase inhibitors on the induction of apoptosis and oxidative stress via the Abl-mediated MAPK signalling pathway in chronic myeloid leukaemia

Verbascoside (Verb) may exhibit potential antitumour activities in leukaemia. The present study investigated the effect of Verb, in combination with imatinib (IM), dasatinib (Das), lipopolysaccharide (LPS) and TNF, on cell survival, Abl expression, apoptosis, oxidative stress and the MAPK pathway in chronic myeloid leukaemia (CML) cells. Cell viability was determined using the WST-8 assay in K562 and R-K562 cells treated with Verb and/or IM, Das, LPS and TNF. Apoptosis and DNA damage in CML cells was detected by caspase-3 and comet analysis. The protein levels of Abl (Phospho-Tyr412), and total/phosphorylated p38, JNK and ERK in CML cells were analysed using a Colorimetric Cell-Based Assay. Oxidative stress was examined using total antioxidant and oxidant status assays. Treatment with Verb and/or tyrosine kinase inhibitors (TKIs), LPS and TNF resulted in a significant decrease in the Tyr-412 phosphorylation of Abl in K562 and R-K562 cells. In addition, cotreatment with Verb and IM or Das additively induced apoptosis by activating caspase-3 levels in both cell lines. Activation of p38 and JNK can result in growth arrest and cell death, whereas ERK stimulation results in cell division and differentiation. The present study demonstrated that cotreatment with Verb and TKIs suppressed phosphorylated-ERK1/2, whereas the levels of phosphorylated-p-38 and phosphorylated-JNK were significantly elevated by Verb and/or IM, Das, LPS and TNF, thus suggesting that Abl and Src inhibition could be involved in the effects of Verb on MAPK signalling in R-K562 cells. Furthermore, Verb elevated reactive oxygen species levels additively with TKIs in both cell lines by increasing the oxidant capacity and decreasing the antioxidant capacity. In conclusion, anti-leukemic mechanisms of Verb may be mediated by Abl protein and regulation of its downstream p38-MAPK/JNK pathway, caspase-3 and oxidative stress in CML cells

Investigation of the Effects of TGF- beta and TGF- beta Inhibitors on Cell Proliferation and Senescence in Human Corneal Endothelial Cells

[No Abstract Available]Pamukkale University Scientific Research Projects Coordination Unit [2020SABE026, 2020TIPF026, 2020HZDP019, 2020HZDP020]This study supported by Pamukkale University Scientific Research Projects Coordination Unit (2020SABE026, 2020TIPF026, 2020HZDP019, 2020HZDP020)

Cisplatin loaded PMMA: mechanical properties, surface analysis and effects on Saos-2 cell culture

Objective: Despite wide resection and systemic chemotherapy, bone tumors may present with local recurrences, metastases and pathological fractures. Application of bone cement containing antineoplastic drug to fill the defect after resection of metastatic lesions and to support implants has been suggested to prevent local tumor growth and implant failures. In this study, we aimed to demonstrate the effects of the addition of cisplatin which is a widely used antineoplastic drug for osteosarcoma, on the mechanical properties of bone cement, and to evaluate the cytotoxic effects of eluted cisplatin on Saos-2 cell culture

Verbascoside Inhibits/Repairs the Damage of LPS-Induced Inflammation by Regulating Apoptosis, Oxidative Stress, and Bone Remodeling

Osteocytes play an important role as regulators of both osteoclasts and osteoblasts, and some proteins that are secreted from them play a role in bone remodeling and modeling. LPS affects bone structure because it is an inflammatory factor, despite verbascoside's potential for bone preservation and healing. Osteocytes may also be involved in the control of the bone's response to immunological changes in inflammatory situations. MLO-Y4 cells were cultured in either supplemented -MEM alone with a low serum to inhibit cell growth or media with LPS (10 ng/mL) and/or verbascoside (50 g/mL) to show the LPS effect. In our research, LPS treatment increased RANKL levels while decreasing OPG and RUNX2 expression. Treatment with verbascoside reduced RANKL expression. In our work, verbascoside increased the expression of OPG and RUNX2. In MLO-Y4 cells exposed to verbascoside, SOD, CAT, and GSH activities as well as the expression levels of bone mineralization proteins like PHEX, RUNX2, and OPG were all elevated.Pamukkale UniversityNo Statement Availabl

Verbascoside Inhibits/Repairs the Damage of LPS-Induced Inflammation by Regulating Apoptosis, Oxidative Stress, and Bone Remodeling

Osteocytes play an important role as regulators of both osteoclasts and osteoblasts, and some proteins that are secreted from them play a role in bone remodeling and modeling. LPS affects bone structure because it is an inflammatory factor, despite verbascoside’s potential for bone preservation and healing. Osteocytes may also be involved in the control of the bone’s response to immunological changes in inflammatory situations. MLO-Y4 cells were cultured in either supplemented -MEM alone with a low serum to inhibit cell growth or media with LPS (10 ng/mL) and/or verbascoside (50 g/mL) to show the LPS effect. In our research, LPS treatment increased RANKL levels while decreasing OPG and RUNX2 expression. Treatment with verbascoside reduced RANKL expression. In our work, verbascoside increased the expression of OPG and RUNX2. In MLO-Y4 cells exposed to verbascoside, SOD, CAT, and GSH activities as well as the expression levels of bone mineralization proteins like PHEX, RUNX2, and OPG were all elevated