Tempol Mitigates Methotrexate-Induced Osteotoxicity via Oxidative Stress Modulation and MAPK Pathway Inhibition

Fariz Selimli,1 Meryem Taş Reyhanioğlu,1 Ahmet can Haskan,1 Muhammed Said Altun,1 Soner Mete,2 Halil Mahir Kaplan3 1Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Mustafa Kemal University, Hatay, Turkey; 2Department of Medical Services and Techniques, Medical Promotion and Marketing Program, Medical Vocational Higher Services School, Nevsehir Haci Bektas University, Nevşehir, Turkey; 3Deparment of Medicinal Pharmacology, Faculty of Medicine, Cukurova University, Adana, TurkeyCorrespondence: Fariz Selimli, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Mustafa Kemal University, Hatay, 01330, Turkey, Tel +905456744444, Email [email protected]: Osteotoxicity, a common consequence of Methotrexate (MTX) therapy, significantly compromises bone health by inducing oxidative stress and disrupting bone remodeling. This study examines the protective effects of Tempol, a nitroxide compound with antioxidant properties, against MTX-induced osteotoxicity.Methods: Osteocyte-like MLO-Y4 cells were cultured and treated with Tempol and MTX to evaluate changes in apoptotic mediators, MAPK signaling pathways, and oxidative stress parameters.Results: MTX treatment significantly increased caspase-3 activity and Bax expression while decreasing Bcl-2 levels, thereby creating a pro-apoptotic environment. It also activated stress-related pathways by elevating JNK and ERK activities. Conversely, Tempol effectively countered these effects by restoring the balance of apoptotic mediators, downregulating MAPK activation, and enhancing Total Antioxidant Status (TAS). Additionally, Tempol reduced Total Oxidant Status (TOS) and improved the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx).Conclusion: These findings highlight Tempol’s potential to mitigate oxidative stress and apoptosis linked to MTX therapy, supporting its use as an adjunctive treatment to protect bone health in patients undergoing MTX therapy. Emphasizing Tempol’s clinical implications as a protective agent reinforces the urgency for further research into its long-term effects on cellular viability and bone integrity in the context of chemotherapy.Keywords: tempol, osteotoxicity, methotrexate, oxidative stress and MAP

Prolonged venous bleeding due to traditional treatment with leech bite: a case report

<p>Abstract</p> <p>Introduction</p> <p>The medicinal leech, <it>Hirudo medicinalis</it>, has been used in the treatment of many diseases for thousands of years. In Turkey, it is used most commonly in the management of venous diseases of lower extremities.</p> <p>Case presentation</p> <p>A 25-year-old Turkish woman presented to our emergency room with bleeding from her left leg. She had been treated for varicose veins in her lower extremities with leeches about 24 hours before admission to the emergency room. The bleeding was controlled by applying pressure with sterile gauze upon the wound, and she was discharged. She returned after four hours having started bleeding again. Hemostasis was achieved by vein ligation under local anesthesia.</p> <p>Conclusions</p> <p>Leech bite should be evaluated as a special injury. Prolonged bleeding can be seen after leech bites. In such cases, hemostasis either with local pressure or ligation of the bleeding vessel is mandatory.</p

Co-Culture of Keratinocyte-Staphylococcus aureus on Cu-Ag-Zn/CuO and Cu-Ag-W Nanoparticle Loaded Bacterial Cellulose:PMMA Bandages

Pressurized gyration and its sister processes are novel methods to produce polymeric fibers. Potential applications for such fibers include wound dressings, tissue engineering scaffolds, and filters. This study reports on a pressurized gyration technique that employs pressured N2 gas to prepare biocompatible wound dressing bandages from bacterial cellulose and poly (methylmethacrylate) polymer blended with alloyed antimicrobial nanoparticles. Resulting bandages are manufactured with high product yield and characterized for their chemical, physical, and mechanical properties. Increased density in solutions with additional antimicrobial nanoparticles results in increased fiber diameters. Also, addition of antimicrobial nanoparticles enhances ultimate tensile strength and Young's modulus of the bandages. Typical molecular bonding in the bandages is confirmed by Fourier-transform infrared spectroscopy, with peaks that have higher intensity and narrowing points being caused by additional antimicrobial nanoparticles. More so, the cellular response to the bandages and the accompanying antimicrobial activity are studied in detail by in vitro co-culture of Staphylococcus aureus and keratinocytes. Antimicrobial nanoparticle-loaded bandage samples show increased cell viability and bacteria inhibition during co-culture and are found to have a promising future as epidermal wound dressing materials

Single left coronary artery with separate origins of proximal and distal right coronary arteries from left anterior descending and circumflex arteries – a previously undescribed coronary circulation

A single left coronary artery with right coronary artery arising from either left main stem (LMS) or left anterior descending artery (LAD) or circumflex artery (Cx) is an extremely rare coronary anomaly. This is the first report of separate origins of proximal and distal RCA from LAD and circumflex arteries respectively in a patient with a single left coronary artery. This 57 year old patient presented with unstable angina and severe stenotic disease of LAD and Cx arteries and underwent urgent successful quadruple coronary artery bypass grafting. The anomalies of right coronary artery in terms of their origin, number and distribution are reviewed