Background. The intestinal barrier is a crucial structure for maintaining the balance in permeability of digested food and restriction of microbial invasion from internal environment. Imbalance in these functions closely related to the initiation of intestinal epithelium reactivity and inflammation. Inflammation is the most common cause of intestinal dysfunction. Muramyl peptides (MPs) are small signaling molecules which stimulate intracellular receptors of pathogens and are potent regulators of cell response. However, molecular mechanisms of MP effect on intestinal cells remain unknown. The study of MP application to maintain viability of Caco-2 cells was aimed to explore the cytoprotective effect of MP-based probiotic on gut inflammation and intestinal barrier integrity. Materials and methods. Caco-2 cells were treated with 10–100 µg/ml lipopolysaccharide (LPS), 5–50 µg/ml MPs and combination of LPS + MPs. Cell viability was measured with MTT assay. Occludin content was detected with Western blotting. Enzyme-linked immunosorbent assay was applied to assess interleukin-8 (IL-8) production. Results. Obtained results have shown that LPS treatment with doses of 10–100 µg/ml induced in a decrease in cell viability and occludin content. On the contrary, IL-8 content was increased in LPS treatment that evidence the dose-dependent proinflammatory changes in Caco-2 cells. No significant changes were detected in the cells exposed to 5–50 µg/ml doses of MPs. However, application of 50 µg/ml of MPs inhibited IL-8 upregulation in LPS-exposed cells. Besides, MPs exhibited a dose-dependent cytoprotective effect in respect to cell viability at a dose of 20 and 50 µg/ml. Furthermore, MP dose of 50 µg/ml helped restore occludin content in LPS-exposed cells. Conclusions. Taking into the account that occludin is one of major components of tight junctions, MPs can restore epithelial barrier integrity in compromised gut. Observed results demonstrated that MPs is a promising agent in inflammation-induced intestinal injury and maintaining gut barrier function.

Porcine epidemic diarrhea virus (PEDV) causes immensely large economic losses in the worldwide swine industry. PEDV attacks the intestine, disrupts intestinal epithelium morphology and barrier integrity, and results in profound diarrhea and high mortality. A commercially available isotonic protein solution (IPS) (Tonisity Px) has anecdotally been reported to be effective in supportive treatment of piglets with active PEDV infections. This study evaluated the effects of supplementing (or not) the drinking water of 14 day old PEDV-infected piglets with the IPS on the content of E-cadherin, fibronectin, interferon-alpha (IFN-α), and matrix metalloproteinase 9 (MMP-9) in duodenal tissue. The content of PEDV DNA in feces was also measured. Though both groups had similar PEDV shedding at day 1, IPS piglets had significantly lower PEDV shedding at day 5, 14 and 21. The IPS group also had a shorter duration of PEDV virus shedding.Levels of E-cadherin and fibronectin, both of which are structural proteins in the intestine, remained unchanged from baseline in the IPS group, whereas the same molecules decreased significantly in the control group. IFN-α, an antiviral cytokine, and MMP-9, an enzyme that aids in tissue remodeling, were increased at days 5 and 14 post infection, and then decreased at day 21 post-infection in the IPS group compared to control.Overall, the IPS used in this study enhanced epithelial intercellular adhesion (E-cadherin) and extracellular matrix structure (fibronectin), resulted in significantand favorable changes in MMP-9 activity, and favorably modulated IFN-α production.This is the first report of this panel of biomarkers, especially MMP-9 and IFN-α, in the face of in vivo PEDV infection. This is also the first report to investigate a commercially available swine product that does not need to be administered in solid feed, and that is already registered for use throughout Asia, Europe, South America, and North America.Overall, the results of this study serve to clarify the behavior of 4 key biomarkers in the presence of in vivo PEDV infection. The results also indicate that IPS (Tonisity Px) supplementation is a viable intervention to modulate the porcine intestinal immune response with favorable effects on the intestine.

Myxomatous degeneration of the mitral valve, or endocardiosis, represents the most prevalent cardiovascular pathology among small- and medium-sized dog breeds. The disease is chronic, with clinical signs possibly emerging over a period of 3-4 years from the initial involvement of the mitral valve leaflets. The primary therapy initiates at stage B2, according to the ACVIM consensus which is characterized by the absence of clinical signs. In our research, animals were chosen based on a medical history indicating symptoms including episodic coughing, decreased tolerance to physical exertion, and instances of dyspnea during periods of rest or sleep. A total of 12 animals presenting with pathognomonic signs of heart disease were investigated. The diagnosis was confirmed using echocardiography, and the animals were conditionally divided into one control and two exposed to humic acids formulation groups. The results of an echocardiographic investigation regarding the functional status of the heart in diseased animals treated with bioactive substance of humic origin are provided. During the 21 days the second experimental group was administered the "Humilid" preparation at a dosage of 10 mg/kg of active substance once daily. Echocardiographic measurements were performed at the onset of the study and on the 21st day of the investigation. Obtained results demonstrated that exposure to “Humilid” with the standard therapy on the 21st day of study improves the functional parameters of the heart. Specifically, there was observed a reduction in left atrial and left ventricular dilation by 12.5% and 11.8%, respectively, although statistically insignificant (p > 0.05). Nevertheless, the treatment with humic acids led to a decrease in severity of clinical symptoms. No effect of bioactive substances contained humic acids was observed in respect to the ejection fraction and fractional shortening. Aforementioned parameters were unaltered in both groups within the reference norms throughout the. Furthermore, no adverse or toxic impact of the humic acids formulation on the detected physiological parameters of the animals were observed. The findings from our study may serve for a comprehensive evaluation of the risk related to the development of stagnant phenomena, as well as in finding out the effects of humic substances on myocardial function and cardiac physiological properties.

The main task for the effective breeding of productive animals is obtaining viable offspring and ensuring the appropriate functional status of the organism during all stages of ontogenesis 1 .The most important while of the organism development is a period of early postnatal adaptation 234 .In Ukrainian pig farms, this adaptation time is one of the main periods during when a high percentage of neonatal piglet mortality is observed 5 .One of the reasons for this problem caused with non-infectious pathology of the digestive and respiratory tracts 6 .This is due to a low level of the innate immunity caused with the increase some technological limitations, the stress induced by various etiologic factors, and the disruptions in the technology of rearing breeding sow.The combined effect of these factors leads to the destruction in the fetal period of organism development, a lack of colostrum quality, and is accompanied by the immunodeficiency changes in newborn piglets 7 .1 Oster, M.

МОДУЛЯЦІЯ ІМУНІТЕТУ ТА БАРЄРНОЇ ФУНКЦІЇ У ПРЕ-І ПОСТНАТАЛЬНОМУ ОНТОГЕНЕЗІ ТВАРИН. РОЛЬ ЕНТЕРОЦИТІВ У ЗАБЕЗПЕЧЕННІ БАРЄРНОЇ ФУНКЦІЇ КИШЕЧНИКА У ПЛОДОВИЙ

Non-specific protection of the animal body are represented by various proteins and peptides 1 .They are present in the various biological fluids and circulate in the blood of animals in the significant amount to maintain the homeostasis 2 .These factors have antimicrobial properties or have the ability to activate other humoral and cellular immune defense mechanisms 3 .Immunoglobulins, namely antibodies, are the group of soluble glycoproteins that persist in peripheral blood and biological fluids 4 .They have the ability to interact with antigens and thus cause neutralization of the latter 56 .This specific recognizing is accompanied by the antigen-antibody immune complex formation, which circulate in the blood for a while 7 .

Searching for modern strategies to ensure productive parameters in the context of modern requirements for the relatively limited use of antibiotics as growth stimulants is relevant for the pig breeding industry. First and foremost, maintaining intestinal health is the main goal of products that have beneficial effects on the productive animals' health. Monitoring the intestinal system state and timely responding to the development of enteropathogens is essential in the context of limited antibiotics usage. Molecular markers of the intestinal system are promising tool for monitoring the basic functions of the intestine, including the intestinal barrier. Given the fact that protection against enteropathogens is provided by specialized cell-cell and cell-extracellular matrix adhesions, changes in the content of intercellular adhesion proteins may reflect the intestinal barrier density. Fatty acid mixtures are considered to be one of the promising alternatives to the antibiotics use in animal farming. In order to determine the intestinal barrier function status, the modulation of fibronectin content as the extracellular matrix marker in piglets was determined after consumption of a short-chain fatty acid-monoglyceride mixture (SCA-M). Сontrol group of animals consumed a standard diet. The experimental group received a mixture of SCA-M at a dose of 5 g/kg for 4 weeks. The fibronectin content was determined by immunoblotting in the small intestine tissue of the control and experimental groups piglets. It was shown that the fibronectin content in piglets of the experimental group was significantly higher (P < 0.05) compared to the control group. The determination of total protein in the blood serum and intestinal tissue extracts of piglets did not reveal a significant difference between the control and experimental groups. Comparative analysis of the average daily weight gain showed a tendency to a more progressive increase in piglet weight. In general, the results obtained indicate a beneficial SCA-M effect on the fibronectin content modulation and intestinal barrier density maintenance in piglets. Comprehensive molecular markers studies of the piglet intestinal system will be useful for the advance of antibiotic-free strategies in accordance with modern pig breeding requirements.

Dear Colleagues, We are delighted to share another issue (September 2023, Volume 29, Issue 3) of the European Journal of Therapeutics (Eur J Ther). We believe this issue’s valuable and exciting works will be read with interest. As you will notice at first glance, you will see that this issue contains many editorials and letters to the editor, unlike the previous issues. As the new editorial team, we aim to publish current developments, interesting notes, or important historical anecdotes in medicine as Editorials, Special Editorials, or Letters to the Editor. We would like to inform you that you can submit all of your articles that meet these criteria to our journal. In this editorial, we would like to share the developments that we think are important for Eur J Ther, since our previous editorial [1]. First, we would like to share that the Eur J Ther is approved for inclusion in ERIH PLUS [2]. Moreover, the Eur J Ther now also appears in the Journal Section of the ResearchGate [3]. In this way, it will be possible to follow the Eur J Ther through ResearchGate. We wish to inform you that our editorial team is diligently striving to deliver enhanced advancements in the forthcoming editions. Another significant development is that an application to the Index Copernicus was submitted for the Eur J Ther on July 31, 2023 [4]. In the previous issue, it was reported that some of the cited references made to the previous articles published in the Eur J Ther were not reflected in the Web of Science, and applications via “data changes form” were made to correct them [1]. Most of these applications have been completed, updated in the Web of Science database, and corrected missing references. With these corrections and new citations in the last three to four months, the average per-item value (total number of citations for all articles divided by the number of articles) of the Eur J Ther has increased from 0.52 to 0.78 [5]. In addition, the journal’s H-Index has risen from 8 to 10. The current metrics of Eur J Ther in the Web of Science are as follows, as of August 16, 2023 [5]. Total number of publications: 800 (between 2007 to 2023) Citing Articles (total): 593 Citing Articles (without self-citations): 558 Times Cited (total): 620 Times Cited (without self-citations): 570 Average per item: 0.78 (620/800) H-Index: 10 Although these metrics may be insufficient for Eur J Ther, which has been published for over thirty years, we, the New Editorial Team, anticipate that we can achieve better levels in the long run with our updated policies. Another significant development is that the Journal Impact Factor value of the Eur J Ther was calculated for the first time, and this value was 0.3. As is known, the Web of Science calculated Journal Impact Factors for the first time for journals in the E-SCI index as of 2023 [6]. Although a Journal Impact Factor of 0.3 is not satisfactory, it is not bad for a journal whose Journal Impact Factor is calculated for the first time. On the other hand, we believe that this value will increase in the coming years, as essential and valuable studies will be published in our journal. The previous issue reported that there are significant changes in the Editorial Board of Eur J Ther [1, 7]. We are pleased to inform you that we continue to expand our editorial team in this issue. Information about our esteemed editors, who have recently joined our team, is below. Ricardo Grillo, DDS, MBA, MSc, is a new Editorial Board Member of the Eur J Ther for Oral and Maxillofacial Surgery. Dr Grillo is the Head of the Department of Oral and Maxillofacial Surgery at IPESP (Brasília). He has more than 20 years of experience in Orthognathic Surgery, Oral Surgery and Maxillofacial Aesthetics. He is also a court expert in the topic. His special interest is related to new technologies including algorithms, virtual surgical planning, CAD and biotechnology. Figen Govsa (Gokmen), MD, finished her higher education at the Faculty of Medicine at Dokuz Eylul University in Izmir between 1982 and 1988. In 1989, she worked as a general practitioner at the Cal Health Center in Denizli Province. From 1990 to 1992, she served as an assistant at the Department of Anatomy at Ege University’s Faculty of Medicine. She worked as an associate professor at the Department of Anatomy between 1996 and 2001, and since 2001, she has been a professor. She has served in various faculty and upper management positions in Ege University’s institutional structure, continuing her education-focused administrative roles in several councils and committees at the Faculty of Medicine. She has contributed to undergraduate and postgraduate education across Ege University’s faculties, mentoring master’s, doctoral, and specialist students, helping them become academics in the field of anatomy. Her research interests include clinical anatomy (surgical anatomy, head and neck surgery, vascular surgery, reconstructive surgery), radio-anatomy, anatomy teaching, and personalized treatment algorithms. She is the founder of the Digital Imaging and Three-Dimensional Modeling Laboratory- Ege 3D Lab (www.ege3dlab.com), where personalized surgical plans have increased surgical success in complex cases involving orthopedics, general surgery, neurosurgery, eye surgery, radiation oncology, and thoracic surgery. With 150 SCI-expanded indexed academic journal articles, she has served as editor and chapter author for several scientific books published by national and international publishers. She has been an executor and researcher on numerous national projects in collaboration with national and international scientists. She is the Education and Terminology theme editor of the Surgical Radiological Anatomy journal and serves as an editor and reviewer for many foreign journals. She was the only anatomist from Turkey to be included in Stanford University's list of the World's Most Influential Scientists. Her joint publication with Prof. Dr. Yelda Pınar, titled "Anatomy of the superficial temporal artery and its branches: its importance for surgery", was ranked among the top 50 most-cited articles in the face rejuvenation theme by Mayo Clinic's Department of Plastic Surgery since 1950. It's the only study from Turkey in the "Landmarks in Facial Rejuvenation Surgery: The Top 50 Most Cited Articles. Aesthet Surg J, 2020." From 2010 to 2012, Govsa contributed as a member of the TÜBA Turkish Medical Terminology Dictionary Working Group and was invited to rejoin the TÜBA working group starting in 2021. Since its establishment, she has been a member of the Turkish Anatomy and Clinical Anatomy Association, serving on its Qualification Board and Ethical Committee. She is also a member of the European Clinical Anatomy Association (EACA). Özgür Kasapçopur, MD, is a Professor in Pediatrics at Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Department of Pediatrics, and is currently Head of Pediatric Rheumatology. He serves as the Chairman of the Institutional Review Board and Clinical Research Ethical Committee of Cerrahpasa Medical Faculty. Professor Kasapçopur received his undergraduate education in Medicine at Istanbul University, Cerrahpasa Medical Faculty and also completed here both his residency and fellowship in the Department of Pediatrics. Professor Kasapçopur is a member of the Pediatric Rheumatology European Society (PReS), the Pediatric Rheumatology International Trials Organization (PRINTO), the Turkish Pediatric Association and the Turkish National Society of Pediatric Rheumatology. Professor Kasapçopur’s research interests include vaccine response, cytokine pathway, and medical ethics, with clinical emphases on juvenile idiopathic arthritis, familial Mediterranean fever, autoinflammatory disease and juvenile systemic lupus erythematosus, dermatomyositis and scleroderma. Professor Kasapçopur has published 83 book chapters in Turkish medical textbooks, and more than 315 original peer-reviewed articles (and case reports) in medical journals. The h-index of Professor Kasapçopur is 55 in Google Scholar and 43 in Web of Science. He had more than 8800 citations in the Web of Science. Professor Kasapcopur is Editor-in-Chief of Turkish Archives Pediatrics. Additionally, Professor Kasapcopur is the Associate Editor of Archives of Rheumatology, Frontiers in Pediatrics, and Case Report in Pediatrics. He is also on the editorial board of many scientific national and international journals. Harry Pantazopoulos, PhD is a faculty member in the Department of Psychiatry and Human Behavior at the University of Mississippi Medical Center. Dr Pantazopoulos received his A.L.M. degree from Harvard University and his doctoral degree in Neurobiology from Northeastern University in Boston. He trained as a postdoctoral fellow and a Junior Faculty at Mclean Hospital, Harvard Medical School before joining the University of Mississippi. The research of the Pantazopoulos lab is focused on identifying the neuropathological correlates of psychiatric disorders with an emphasis on the role of the extracellular matrix and circadian rhythms. He pursues these questions using a combination of human postmortem and animal model approaches. His long-term research goal is to develop a foundation of changes in neurocircuitry in several diseases, including Autism Spectrum Disorders, Schizophrenia, Bipolar Disorder, Major Depression and Substance Use Disorders, that he can leverage to develop more effective treatments. In addition, he aims to identify basic biological mechanisms that will provide insight into how the circadian system and the extracellular matrix regulate neural functions in a brain region-specific manner, linked to specific behaviors. Ghada Shahrour, PhD, PMHCNS, RN is a faculty member at the Faculty of Nursing in Jordan University of Science and Technology. She is an associate professor in the field of psychiatric nursing and currently is the Chairman of the Community and Mental Health Nursing Department. Dr Shahrour received her PhD in 2017 and Master’s degrees in 2011 from Kent State University in the USA and her BSN from Jordan University of Science and Technology. Her research interest is in the area of mental health nursing and more specifically researching bullying among adolescent school children and college students. Although Dr Shahrour has been appointed in 2018 to work at Jordan University of Science and Technology, she has 30 publications so far in the field of mental health. Dr Shahrour is a co-founder and a previous vice president of the Psychological Sciences Association in Jordan. She has worked on national and international projects as a co-investigator. Dr Shahrour aspires to improve the lives of adolescents and college students through her research on bullying and mental health in general.

Dear Colleagues, In the previous editorial paper published by Balat et al. [1] as an Early View Article a few months ago, it was reported that there were changes in the Editorial Team of the European Journal of Therapeutics (Eur J Ther). During these few months, while the preparations for the new issue (June 2023, volume 29, Issue 2) continued, the editorial board also was revised. We would like to inform you that the Editorial Board has been strengthened by academics who are competent in their fields from many countries of the world and will continue to be strengthened in the future. As it is known, Eur J Ther started broadcasting in 1990 as a Journal of the Faculty of Medicine University of Gaziantep (In Turkish: Gaziantep Üniversitesi Tıp Fakültesi Dergisi). In the first paper titled “While Starting” (In Turkish: Başlarken) of the first issue, Prof. Sabri Güngör, who was the first Editor-in-Chief, stated that the aim of the journal is to have an influential place in the field of science [2]. Over the past three decades, the journal has continued to advance. At the present time, it is inevitable to reorganise the editorial board of the journal and enrich it with leading international editors in order to move the journal to better places. This editorial will explain essential developments in the journal in the last few months, and the new Editorial Board Members of the Eur J Ther will be introduced. Changes are inevitable, and we are delighted to announce that this issue marks several significant improvements. Specifically, we bolstered our editorial team with esteemed international academics and expanded our pool of referees. Consequently, the evaluation period for the submitted articles was significantly reduced. In the last two months, the journal metrics are as follows: Acceptance rate: %29 Average time until the final decision: 24.4 days Average time to publish as Accepted/Early View Article, after acceptance: 4.8 days. Thanks to these improvements, as you will notice, there are 25 articles in this issue. In this way, this issue has been the issue in which most articles have been published so far. In addition, applications were made to DOAJ (Directory of Open Access Journals) and BASE (Bielefeld Academic Search Engine), among the most essential open-access databases in the world, in May 2023. Moreover, cited references to the previous and/or alternative names of the journal (Gaziantep Medical Journal, Gaziantep Med J, Gaziantep Tıp Dergisi and Gaziantep Üniversitesi Tıp Fakültesi Dergisi) in Web of Science that were not reflected in the journal metrics were identified and reported to the Web of Science. Some of these correction requests have been finalized and corrected, and thus the total number of citations and the H-index of the journal increased [3]. After all these data are updated, it will be seen that the citation values of the Eur J Ther will increase even more. We will also update the guidelines for the authors and reviewers with respect to the ICMJE [4] and EQUATOR Network [5], which will enhance the quality of research in the medical fraternity. Additionally, the use of DOI for articles published in the journal started in 2011 (2011, volume 17, Issue 2). In order to facilitate the recognition and access of the articles, DOIs have also been defined for all articles published in previous issues. Editors Ayşe Balat, MD, became the new Editor-in-Chief of Eur J Ther for the second time, the first between 2007-2010. She is a Professor in Pediatrics and a specialist in Pediatric Nephrology and Rheumatology. She has been working as Vice President of Gaziantep University since October 2020. She was the Dean of Gaziantep University Medical Faculty (2007-2010), President of the Mediterranean Kidney Society (MKS) between 2015 to 2018, and Secretary beginning in 2018. She is also President of the International Association for the History of Nephrology (IAHN) since 2022. In Gaziantep, she first established Pediatric Nephrology and Pediatric Rheumatology Units, and the first peritoneal dialysis was performed by her. She has several studies published in international and national peer-reviewed scientific journals (H-Index: 26, i10-index: 59 and approximately 2500 citations). She was the Guest Editor of the International Journal of Nephrology in 2012 (special issue titled “Devil’s Triangle in Kidney Diseases: Oxidative Stress, Mediators, and Inflammation”). She is a member of many national and international associations related to her field, including membership in the Turkish Pediatric Nephrology Association board in the past. She has several scientific presentation awards at national and international congresses. She has been joined as an “invited speaker” at 20 International Meetings. As of 2007, she organizes World Kidney Day activities within the scope of the “Survival is not Enough” program (in the first rank among European pediatric nephrologists as an organizer of those activities). Recently, she was elected as a “lifelong member of the Academy of Medicine and Surgical Sciences” of the University of Naples, which is one of the four important academies in Naples. Şevki Hakan Eren, MD, is the new Deputy Editor-in-Chief of the Eur J Ther. Dr Eren graduated from the Medical School, University of Gaziantep, Turkey and completed Emergency training at Cumhuriyet University. He has been working as a Professor at Gaziantep University, Department of Emergency Medicine, Gaziantep, Turkey. He is interested in traumatology, and toxicology. Mehmet Sait Menzilcioğlu, MD, is the new Deputy Editor-in-Chief of the Eur J Ther. Dr. Menzilcioğlu graduated from the Medical School, University of Gaziantep, Turkey and completed Radiology training at the same University. He has been working as an Associate Professor at Gaziantep University, Department of Radiology, Gaziantep, Turkey. He is interested in neuroradiology, ultrasonography, doppler Ultrasonography, Computerized Tomography, Magnetic Resonance Imaging, interventional radiology, and obstetric sonography. İlhan Bahşi, MD, PhD, is the new Deputy Editor-in-Chief of the Eur J Ther. Dr Bahşi is also on the Editorial Board of the Journal of Craniofacial Surgery, Frontiers in Neuroanatomy, and Mersin University School of Medicine Lokman Hekim Journal of History of Medicine and Folk Medicine. In addition, he has published more than 80 articles (H-index: 12 and i10-index: 15) and has been a referee for more than 600 academic papers in many internationally indexed journals. Dr Bahşi, who has been working in the Department of Anatomy at the Gaziantep University Faculty of Medicine since 2012, completed his doctorate education in 2017 and obtained the title of PhD. Besides anatomy, he is particularly interested in the history of medicine, medical ethics, and education. İlkay Doğan, PhD, is the new Editorial Board member of the Eur J Ther for Statistics and Methodology. He is in the Department of Biostatistics at the Gaziantep University Faculty of Medicine. His professional focus lies in research about Structural Equation Modeling, Multivariate Analysis. With a wealth of experience spanning over 15 years across multiple disciplines, including veterinary, nursing, sport and medicine, Dr Doğan has held various notable articles. He is a member of the Turkish Biostatistics Association. Ahmet Acıduman, MD, PhD, graduated from Ege University Faculty of Medicine in 1987 and later specialized in Neurosurgery in 1997. Dr Acıduman further expanded his academic credentials by completing a PhD in the History of Medicine and Ethics in 2005. Currently, he is a Professor in the Department of History of Medicine and Ethics at Ankara University Faculty of Medicine. With a notable record of over 200 academic publications, Dr Acıduman’s contributions to the field continue. Bilal Çiğ, PhD, is a new Editorial board member of the Eur J Ther. Associate Prof Bilal Çiğ is a Postdoctoral researcher at King's College London Wolfson Card. He has been investigating the roles of ion channels in neurological diseases using the patch clamp technique for nearly 15 years. For the past few years, he has focused on the interactions of TRPA1 and Kir 4.1 channels in demyelination. He has 40 SCI-E and international publications, with about 1300 citations. Tsvetoslav Georgiev, MD, PhD, holds an esteemed position as an associate professor at the First Department of Internal Medicine in Varna, Bulgaria, while also working as a clinician at the University Hospital St. Marina. He has successfully defended his doctoral dissertation in 2018 at the Medical University in Sofia. Having obtained a specialization in rheumatology that same year, Dr Georgiev has extensive expertise in this intricate field of medicine. He further expanded his knowledge and skills by attending comprehensive courses on imaging diagnostics and musculoskeletal ultrasound in rheumatology held in various locations. Dr Georgiev has been involved in formulating the Bulgarian consensus on osteoarthritis and EULAR recommendations for the non-pharmacological core management of osteoarthritis. Notably, Dr Georgiev has received recognition for his outstanding contributions as a reviewer, earning awards in 2019 and 2021 from the Korean Academy of Medical Sciences. Davut Sinan Kaplan, PhD, is a new Editorial Board Member of the Eur J Ther. Dr Kaplan is an Associate Professor in the Department of Physiology at Gaziantep University Faculty of Medicine. He is also the Graduate School of Health Sciences’ Director. He has taken involved in a wide variety of research with animal models. His research generally focuses on Endocrinology, Metabolism, Physical Activity, and Breast Milk. He has mentored a large group of master’s and PhD students. He has served for many years as a member of the local animal experiments ethics committee. Mehmet Karadağ, MD, is a new Editorial Board Member of the Eur J Ther for Psychiatry. Dr. Karadag is an Associate Professor of Child and Adolescent Psychiatry. He is in the Department of Child and Adolescent Psychiatry at the Gaziantep University School of Medicine. He has experience on Posttraumatic Stress, Attention Deficit Hyperactivity, Autism Spectrum, Anxiety, Depressive Disorders and EMDR Therapy. He is also EMDRIA accredited EMDR Consultant. Murat Karaoglan, MD, is a new Editorial Board Member of the Eur J Ther for Endocrinology. Dr. Karaoglan is an Associate Professor of Pediatric Endocrinology. He is in the Department of Pediatric Endocrinology at the Gaziantep University School of Medicine. He has experience on growth disorder, diabetology and disorder of sexual development. Waqar M. Naqvi, PhD, is a faculty in the Department of Physiotherapy at the College of Health Sciences, Gulf Medical University, Ajman, UAE. His professional focus lies in the development of the research ecosystem within healthcare education, with a particular interest in AI, AR, VR, Sensors, and innovation in health sciences. With a wealth of experience spanning over 14 years across multiple countries, including India, Canada, Cameroon, Hong Kong, and Saudi Arabia, Dr Naqvi has held various notable positions. These include his roles as the Associate Director of Research at the NKP Salve Institute of Medical Sciences, Acting Dean and Vice Dean of the Physiotherapy College, Convener for the International Admission Office, International Accreditation and Quality Assurance Wing, Staff Selection Committee, and Coordinator for a Staff-Student Exchange Program. In recognition of his outstanding contributions, Dr Naqvi was honored with the Distinguished Service Award and Young Achiever Award from the Indian Association of Physiotherapy. Dr Naqvi is widely recognized for his expertise in conducting seminars and workshops on research, publications, and intellectual property rights. Specializing as a research trainer in the fields of medicine, dentistry, physiotherapy, and health sciences, Dr Naqvi's unwavering commitment to research excellence and his genuine passion for mentoring aspiring researchers are instrumental in shaping the future of healthcare. He firmly believes in the power of evidence-based practice and actively advocates for its implementation. Ali Nasimi is a neuroscientist in the field of central regulation of the cardiovascular system. Victor Nedzvetsky, PhD, DrSc is a full professor of Physiology, Biochemistry and Lab Diagnostics, where coordinates courses on Neurochemistry, Molecular and Cell Biology. Additionally, he is a vice-director of “The Biosafety Center” research and development company (Ukraine). He obtained PhD in biochemistry at Dnipropetrovsk University, Ukraine (1990). After postdoctoral training, he received a degree of Doctor Science at Kyiv National University (2006). Since 2015 he was involved as an invited professor of Bingol University, Turkey as a supervisor of PhD projects on genetic and molecular biology. He has participated in both the education and research work of the Dept. Art and Science of Bingol University from 2015 to 2021. His current research interests are focused on intestinal barrier function, brain blood barrier, astrocytes, cognitive deficits, bioactive compounds as anticancer agents, nanomaterials, and neuroprotection. He is the author of over 230 research publications and ten patents. He is a member of the editorial board of the journal “Regulatory Mechanisms of Biosystems”. Raphael Olszewski, DDS, MD, PhD, DrSc is a full professor of oral surgery and dentomaxillofacial radiology at the Université Catholique de Louvain (UCLouvain), Brussels, Belgium. Professor Olszewski is an oral surgeon and member of the Department of Oral and Maxillofacial Surgery at Cliniques Universitaires Saint Luc, UCLouvan, Brussels, Belgium. Prof Olszewski is the Editor-in-Chief of NEMESIS: Negative effects in medical sciences: oral and maxillofacial surgery. Janusz Ostrowski, MD, PhD. Internal medicine, nephrology, and public health specialist. Former Head of the Department of Internal Medicine and Nephrology at the Provincial Hospital in Wloclawek, Poland. Director for Peritoneal Dialysis in Diaverum Company Poland. Secretary of the Historical Section of the Polish Society of Nephrology. Former President of the International Association for the History of Nephrology. Professor, Vice Dean of the School of Public Health and Head of the Department of the History of Medicine in the Centre of Postgraduate Medical Education in Warsaw, Poland. Ayşe Aysima Özçelik, MD, is a new Editorial Board member of Eur J Ther for Neurology. She is the head of the pediatric neurology department and works at Gaziantep University Faculty of Medicine. She is the regional manager for the treatment of spinal muscular atrophy disease. She is an experienced physician in the treatment and follow-up of genetic neurological disorders, epilepsy, and neuromuscular diseases. Maria Piagkou, DDS, MD, MSc, PhD is a new Editorial Board member of Eur J Ther for Neurology. She is an associate professor at the Department of Anatomy, School of Medicine, Faculty of Health Sciences, National and Kapodistrian University of Athens. She is a Deputy Vice-President of the Hellenic Association of Public Health in Greece and a President of the printed material handling committee of the National Organization for Medicines. She has twenty-one years of teaching activity in the field of anatomy, focused on head and neck, oral and maxillofacial area, as well as on skull base anatomy and anatomical variants. Her main areas of interest are head and neck anatomy and surgery, skull base anatomy, oral surgery, maxillofacial and dental trauma, rehabilitation, intraoral fixation after condylar fractures, and teeth replantation. She is an associate editor in 2 journals of Anatomy and acts as Editorial Board Member in six other journals. She authored six chapters in neuroanatomy and oral and maxillofacial surgery and thoracic surgery books, two monographs, and edited the translation of 9 books. She is a reviewer in 30 international scientific journals. She authored 156 publications in PubMed, 91 abstracts in 26 international congresses, and 318 abstracts in Greek scientific meetings. She is General Secretary of the Sports Medicine Association of Greece and treasurer of the Hellenic Association of Anatomy. Halima Resić, MD, PhD is a Professor of Internal Medicine – Nephrology in Sarajevo. Professor Resić studied medicine at the University of Belgrade where she also undertook a clinical fellowship in nephrology. She finished her postgraduate studies also at the University of Belgrade in 1987. Professor Resić worked at the Clinical Centre of Belgrade from 1972 to 1992. In 1993, she worked at the Marmara University of Istanbul. Also, in the period from 1994 to 1996, she took part in projects for refugees in Munich with the support of the Ministry of Health of the city of Munich. From 1996 till 2019, professor Resić worked at the Clinical Center University of Sarajevo, where she was head of the Clinic of Hemodialysis. In 2001, she obtained her PhD degree in Nephrology. She became a professor at the Medical Faculty of the University of Sarajevo in 2013. Professor Resić published about 180 professional and scientific papers in relevant journals. She has been a president of organizations of a few national congress and nephrology schools, and also an active participant of ERA congress and WCN congress. She has also been invited lecturer in over 60 different international and national congresses. Professor Resić was President of the BANTAO Society (2017-2019), and President of the Mediterranean Kidney Society. She has been President of the Society of Nephrology, Dialysis and Kidney Transplantation in Bosnia and Herzegovina (2010-2020) and also, she is President of Donor’s network of Bosnia and Herzegovina. She is a member of ERA EDTA and ISN, and also a member of the Committee of SRC by ISN. She is a member of the Council of EAPE (European Association of Professor Emerita). She is also vice president of IANUBIH (International Academy of Science and Arts in Bosnia and Herzegovina) and a member of the board of South Eastern Europe by ISN. In her carrier, she obtains many international awards for her work in the field of Nephrology. Aldo Rogelis Aquiles Rodrigues is a new Editorial Board member of Eur J Ther for Neurology. Currently, he is an associate professor in physiology at the Federal University of Triângulo Mineiro, MG, Brazil since 2006. Before that, he worked as a research associate at the Department of Neurophysiology, Madison, USA from 2002 to 2005. He has experience in auditory neurons electrophysiology, enteric neurons and ion channels in general. Domenico Santoro is a Full Professor of Nephrology, Director of the Division of Nephrology and Coordinator of the Nephrology Fellowship Program University of Messina, AOU G. Martino – Messina. He is s a clinical expert in glomerular disorders with a scientific formation at the section of renal Pathology of the CSMC UCLA Los Angeles. He collaborated in genetic studies in glomerular disease. He coordinates as principal investigators several studies in glomerular disease both in clinical/therapeutical as well genetic aspects. He is the Associate Editor of the Journal of Nephrology and MBC Nephrology. Author of more than 270 scientific publications indexed on Scopus, H-index in Scopus: 38; H-index in Google Scholar: 46. Onur Taydaş, MD, is a new Editorial Board Member of the Eur J Ther for Radiology. Dr Taydas is an Associate Professor in the Department of Radiology at the Sakarya University School of Medicine. He has a Turkish Society of Radiology Proficiency Certificate, a European Diploma in Radiology, and a Turkish Interventional Radiology Diploma. He has experience in neuroradiology, musculoskeletal radiology, and interventional radiology. Gregory Tsoucalas (or Tsoukalas), born in 1974 and originated from the Island of Skopelos in the center of the Aegean Sea, he had studied Medicine in the University of Saint Kliment Ohridski in Sofia Bulgaria. He had then continued his studies in Lyon France and Athens Greece. He had been a Nuclear Medicine-Oncology-End stage physician in Saint Savvas Anticancer Hospital of Athens. He had after that moved to the city of Volos where he had been a physician in the Saint George Clinic for Alzheimer and Related Dementia Syndromes-End stage. He had finally moved to the General Clinic Anassa of Volos in the Internal Pathology Department. He currently holds the position of the Assistant professor of the History of Medicine, and head of the Department of History of Medicine and Medical Deontology, Medical School, University of Crete, Heraklion, Greece. Specialized in Nuclear Medicine, MSc in Palliative Medicine and PhD in the History of Medicine from National and Kapodistrian University of Athens, History of Medicine Diploma from Claude Bernard Lyon 1 University, post-doc in Anatomy from Democritus University of Thrace, Anthropology Course Diploma from Leiden University. He holds diplomas in Mastology and Clinical Nutrition for the related European Societies. He is the General Secretary of the Hellenic Branch of the Balkan Medical Union. Interested in the fields of History of Medicine, Deontology, Bioethics, Anatomy and Humanities, he is the writer of more than 200 articles in the PubMed database and more than 200 in other bases. He loves books and had published 10, while he had participated with chapters in various publications. Member of the International Society of the History of Medicine he had presented more than 130 speeches and 50 lectures in international level. Member of DELTOS (Hellenic Society) he had presented more than 400 speeches in local level. He enjoys more than 2500 citations, H-index: 17, and i10-index: 41. Hamit Yıldız, MD, PhD, is the new editorial Board member for Internal Medicine. Dr Yildiz is an internal medicine specialist and practices in Gaziantep University Hospital. He is Board Certified in Internal Medicine. He completed his internship at Gaziantep University in Gaziantep and also graduated with a PhD in molecular biology. He has more than ten years of experience as a specialist who focuses on patients with diabetes, hypertension and thyroid diseases. His special interest is recombinant DNA technologies and the development of biotechnological drugs. Betül Yılmaz Furtun, MD, FASE, FAAP, is a new Editorial Board Member for the Eur J Ther. She is an Associate Professor of Pediatrics at the Texas Children's Hospital, Baylor College of Medicine and Associate Medical Director of the Fetal Cardiology/Fetal Cardiac Intervention Program at Texas Children's Hospital. Dr Yilmaz Furtun is also a Course Director of Fetal Cardiology Education/Curriculum Development for advanced and categorical cardiology fellows and an Associate Director of the Fetal Care Center Steering Committee for fetal cardiology at Texas Children's Hospital. Dr Yilmaz Furtun is a pediatric cardiologist with expertise in advanced imaging modalities including fetal echocardiography, transthoracic and transesophageal echocardiography. Dr Yilmaz Furtun completed her pediatrics training at Washington University in St. Louis, pediatric cardiology training at Columbia University Medical Center, New York Presbyterian Hospital, and fetal cardiology/advanced imaging training at Cincinnati Children's Hospital. Dr Yilmaz Furtun actively participates in fetal and pediatric echocardiography laboratory protocol development and fetal and echocardiography lab and Fetal Care Center quality and improvement initiatives. Dr Yilmaz Furtun has been a member of the American Society of Echocardiography, the International Society of Ultrasound in Obstetrics and Gynecology, the Fetal Heart Society as well as American College of Cardiology. Dr Yilmaz Furtun’s clinical and research focus relates to cardiac imaging by echocardiography and fetal echocardiography. She utilizes her experience in these areas to study how we can use non-invasive imaging modalities for investigating normal and abnormal cardiac function in patients with congenital heart disease and in fetuses with cardiac compromise. Her primary research interests focus on fetal cardiovascular assessment and cardiac dysfunction in patients with congenital heart disease, in fetuses with congenital abnormalities, and in multiple gestation pregnancies complicated by twin-twin transfusion syndrome. Matthew Zdilla, DC, is a new Editorial Board Member for the Eur J Ther. Dr Zdilla was educated at the University of Pittsburgh and Northeast College of Health Sciences. He serves as an Associate Professor at the West Virginia University School of Medicine in the United States of America. He is an award-winning, internationally recognized clinical anatomist who has published scores of high-impact research papers regarding human diversity and the impact of anatomical variation on clinical procedures. In addition to his experience as an accomplished researcher, Zdilla brings his experience as an ad hoc reviewer for nearly 40 journals to the European Journal of Therapeutics. Joseph Schmidt, MFA has taught academic writing for the University of Louisville and various campuses of The City University of New York (CUNY). An accomplished poet, he has contributed content to, and edited a number of small literary journals. At Gaziantep University, he has lent his editorial and native English language talents to some of his Turkish colleagues in the sciences. He teaches in the university’s School of Foreign Languages (YDO).

МОДУЛЯЦІЯ ІМУНІТЕТУ ТА БАРЄРНОЇ ФУНКЦІЇ У ПРЕ-І ПОСТНАТАЛЬНОМУ ОНТОГЕНЕЗІ ТВАРИН. РОЛЬ ЕНТЕРОЦИТІВ У ЗАБЕЗПЕЧЕННІ БАРЄРНОЇ ФУНКЦІЇ КИШЕЧНИКА У ПЛОДОВИЙ

Chlorinated benzenesare widely used solvent for various targets including industrial production of adhesives, drugs, rubber, paints and dry cleaning, and as well as fiber-swelling agent in the textile processing. Similar with other thinners chlorobenzeneis potent to induce detrimental effects in different cell types and could cause the functional disorders of the central nervous system. In spite of the progress in xenobiotic toxicity study, the molecular mechanisms of chlorobenzenecytotoxicity remain undiscovered. The search of molecular markers that are potent to characterize toxic risk chronic thinner exposure is an actual task whole world. Cytoskeleton protein expression is modulated with number of the environmental pollutants. Intermediate filament proteins are histology-specific components of cytoskeleton in the mosteukaryotic cells. The glial fibrillar acid protein (GFAP) is a basic component of the astrocyte cytoskeletonand could be used as reliable biomarker of cytotoxicity. Сhlorobenzene effect on mouse CNS and enteric glial cells was studied chronic (30 days) low dose exposure to thinner in vivo model. Obtained results demonstrated that cellular response against thinner toxicity is accompanied by both redox and cytoskeleton disturbance. In the present study, we investigated the GFAP level in the brain and thin intestine to estimate its prognostic value in the model of chlorobenzene chronic intoxication.Prolonged treatment with low doses of chlorobenzene induced in both brain and intestine tissue statistically significant (P < 0.01) upregulation of GFAP and redox imbalance. Observed results have shown that low doses of chlorobenzene develop uniquegliotoxic features in respect to CNS astrocytes and enteric glial cells.

The number of studies related to detailed characteristics of immune system development in early stages of ontogenesis are directed to expansion of concepts of mechanisms of inherent and adaptive immunity in premature newborns. However, discrepancy in publication data and absence of clear conceptions about unique features of immune system in newborn piglets for different gestation periods have significant actuality for further investigation. The study was carried out to establish characteristics of phenotypic and functional characteristics of the immune cells and establishment of adaptive immunity in piglets. The antibody repertoire of sow has interested immunologists for decades, in part because of the ease with which large quantities of high affinity antibodies can be observed in serum, and into other fluids because of the presence of genetic variants for both light and heavy chain of all known immunoglobulin types. The integrative analysis of the cellular and humoral immunity in piglets during early ontogenesis carried out to clarify the exact mechanisms of the immune response modulation. Effectiveness and selectivity of the immunotropic chemicals application to regulate immune cell populations in piglets is presented. The progress in immune cell populations is regulated by the various cytokines production in the universal concentration-dependent manner. Furthermore, the development of the immune functions cross reacts with innate immunity mechanisms including anti-bacterial enzymes, epithelial barrier integrity in the both skin and intestine. The interaction between multiple components of innate immunity is a critic initiator of the dynamic changes in adaptive immunity. The natural resistance targets to the establishment of infection root and delays disease progression. The duration of the exposure to colostrum in important role in the dynamics of immune response as well as its efficacy. The chapter discusses the plural mechanisms so far proposed to be responsible for the modulation natural resistance.

МОДУЛЯЦІЯ ІМУНІТЕТУ ТА БАРЄРНОЇ ФУНКЦІЇ У ПРЕ-І ПОСТНАТАЛЬНОМУ ОНТОГЕНЕЗІ ТВАРИН.ХАРАКТЕРИСТИКА МЕМБРАННИХ БІЛКІВ ІНТЕСТИНАЛЬНОГО ЕПІТЕЛІЯ У

The porcine epidemic diarrhea virus (PEDV) not only causes large economic losses in the swine industry, as the causative agent of PED, but also poses a risk to other animals and human due to cross-species transmission. Piglets are particularly susceptible to PEDV infection, which disrupts intestinal epithelium morphology and barrier integrity as well as nutrient absorption. By supporting innate immunity and intestinal function, isotonic protein solutions (IPSs) may help in restoring the morphology and function of enterocytes after PEDV infection. To this end, the present study evaluated the effects of supplementing (or not) the drinking water of 14-days-old PEDV-infected piglets with an IPS on: the content of E-cadherin, fibronectin (two structural proteins), and interferon-alpha (IFN-α, an antiviral cytokine); the activity of metalloproteinase 9 (MMP-9, an enzyme that degrades the extracellular matrix); and the content of PEDV DNA in the rectum of piglets. The IPS-supplemented group evidenced a less abrupt decrease in E-cadherin and fibronectin and a modulation of IFN-α production and MMP-9 activity. At day 21 post infection, no PEDV DNA was detected in the rectum of piglets supplemented with the IPS. Overall, these results indicate that IPS supplementation is a viable intervention to rehabilitate the intestinal barrier integrity and function and to modulate the immune response. This is possibly done by providing amino acids that promote the metabolism of structural proteins. IPS supplementation is therefore a valid intervention to mitigate the damage inflicted by PEDV on the intestine.

Imidacloprid is one of the most widely used insecticides in the world. The neurotoxicity of imidacloprid in adult amphibians has not been studied thoroughly. We investigated the expression of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and angiostatin in the amphibian brain to identify valid biomarkers of low dose imidacloprid exposure. For the experiment, 30 individuals of the marsh frog Pelophylax ridibundus were selected. The amphibians were divided into five groups. The duration of the experiment was 7 and 21 days. The exposure concentrations were 10 and 100 µg/L. The results of the study revealed a decrease in the expression of GFAP after 7 days in the exposure groups of 10 and 100 μg/L. An increase in the level of NfL was observed in the group exposed to 10 μg/L after 21 days of the experiment. The angiostatin level was increased after 7 days at 10 µg/L and after 21 days at 100 µg/L. The data obtained indicate that low concentrations of imidacloprid can cause neurotoxic effects in the brain of P. ridibundus. Such effects can have a significant impact on amphibian populations. According to the results of the study of the expression level of GFAP, NfL and angiostatin, it can be stated that imidacloprid has a neurotoxic effect on adult marsh frogs. The studied indicators can be promising biomarkers of environmental pollution by neonicotinoids.

The intestinal barrier is an extremely important structure to maintain piglet health. However, various enteropathogens, including coronaviruses, are especially aggressive factors for intestinal barrier destruction. That is why the aim of the present study was to clarify the role of adhesive proteins in the piglet intestinal barrier affected by coronavirus enteric infection. For this purpose, we formed two groups of 14-day-old piglets to construct an experimental model of enteric disorder. Each animal was infected with the porcine epidemic diarrhea virus (PEDV) at a dose of 104 virions. The piglets of the experimental group were additionally fed of isotonic protein mixture (IPM). The intensity of the infectious process was assessed by the duration of virus elimination from the piglets’ body, the amount of excreted virus, and the immune response efficacy. The level of immune response was detected by specific IgG in the blood serum and α-interferon (IFN-α) in the intestinal tissues. The intestinal barrier integrity was assessed by the level of proteins in the tissues that form tight intercellular contacts especially E-cadherin and fibronectin in the duodenum. The results have shown variability in the duration of the PEDV elimination period in piglets’ faeces. The exposure to IPM provides a protective effect that enhances the recovery processes in the intestinal tissues. That was also reflected in an increase in the amount of E-cadherin and fibronectin in the duodenum. Furthermore, the isotonic protein mixture’s protective effect was reflected in an increase in the body’s immune responses at the intestinal level. This effect was evidenced by an increase in the amount of IFN-α in the duodenum and an increase in the synthesis of specific IgG in the blood serum. Obtained results showed a protective effect of IPM treatment while the intestinal barrier and immune responses were enhanced. IPM treatment induced about a 10 times decrease in the amount of PEDV excreted in the faeces of experimental animals and contributed to a 7-day reduction in the virus excretion period.

Heavy metals in model conditions as well as industrial pollution launch disturbances in neural cells of different animals and human beings. The neurotoxicity of mercury, which is one of the most toxic heavy metals, has been studied for several decades. However, its low doses chronic exposure effects for neural tissue cells are still poorly understood. Therefore, the basic molecular mechanisms of mercury should be clarified. The purpose of our research is to clarify the mechanism of mercury genotoxicity, the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in neural tissue cells, and the response to inorganic mercury-induced neurotoxicity. In our model, we used juvenile rainbow trout exposed to mercury chloride with a range of doses 9‑36 µg/L for 60 days to study the cytotoxicity of chronic exposure. We detected the reactive oxygen species (ROS) production as an index of oxidative stress and APE1 as a marker of cellular DNA damage response in a neural cell. The ROS level was measured by using the fluorometric method based on 2',7'-dichlorofluorescein diacetate reaction. The analyses of markers of the DNA repair (APE1) and apoptosis (B cell lymphoma-2 anti-apoptotic protein – Bcl-2) were carried out with western blotting. The mercury chloride chronic exposure induced statistically significant upregulation of the ROS production in the fish brain. Contrary, the mercury low doses stimulated the downregulation of APE1 expression in the brain tissue. Furthermore, mercury chronic exposure inhibited the expression of Bcl-2 in the animals treated with 18 and 36 µg/L mercury chloride. The harmful effect of mercury could be promoted by oxidative stress generation. The downregulation of APE1 expression could lead to a lack of DNA damage response efficacy and initiate the decline in neural cell functioning. Obtained data on the APE1 expression have shown that the neurotoxic effect of mercury could be mediated, at least partially, by the decline in cellular DNA damage response in the brain. The evaluation of decrease in DNA repair response via detection of the APE1 expression can be a prospective tool to reveal the deleterious effects of toxicants in terms of their neuro- and genotoxicity.

Glioblastoma, kemo ve radyoterapiye karşı dirençli, en agresif beyin kanseri tiplerinden biridir. C60 fulleren türevi nanopartiküller, çeşitli modellerde antikanser aktivite amacı ile geliştirilmektedir. Birçok kemoterapi ajanının aksine, bu fulleren çeşitli konsantrasyonlarda toksik değildir. C60 fulleren, birçok biyomedikal uygulama için umut verici bir adaydır. Bu nedenle, suda çözünür hydrated C60 fullerene'in (HyC60Fn) insan glioblastoma U373 hücresinde PARP, Beclin1, LC3 ve GFAP ekspresyonu üzerindeki etkileri araştırılmıştır. Hücre canlılığı ve göçü, sırasıyla MTT ve yara iyileşmesi testi ile belirlendi. PARP, Beclin1 ve LC3 ekspresyonu western blot ile ve GFAP ise immünositokimya ile tespit edildi. 0.5 – 2.0 µM doz aralığındaki HyC60Fn, doza bağlı bir şekilde hücre canlılığını azalttığı belirlendi. Ayrıca, HyC60Fn 1.0 ve 2.0 µM dozları, glioblastoma hücre göçünü belirgin şekilde bastırmıştır. Mekanizma olarak, HyC60Fn'nin otofaji belirteçleri olarak Beclin-1'i ve LC3-II/LC3-I ekspresyon oranını belirgin şekilde yukarı regüle ettiği belirlendi. Ayrıca, suda çözünür HyC60Fn’nin PARP fragmanı ve bu durumun doğal sonuç olarak glioblastoma U373 hücrelerinde parthanatos aktive ettiği belirlendi. Mevcut sonuçlar, HyC60Fn'nin, glioblastoma hücrelerinde şiddetli otofaji akışı ve parthanatos kombinasyonu yoluyla anti-tümör etkisini başlatabildiğini göstermektedir. Bu nedenle HyC60Fn, glioblastoma hücrelerinin reaktivitesini ve programlanmış hücre ölümünü modüle ederek en azından kısmen hücre ölüm mekanizmasını etkiler. Bulgularımız, HyC60Fn 'in umut verici bir kanser karşıtı terapötik olabileceğini ve bu konuda daha fazla çalışmanın gerekli olduğunu göstermektedir.

The applying copper sulphate is a cheap, however it leads to global the environment contamination. Especially, the contamination of the water sources is crucial for fish harvesting and farming. The copper contamination in some areas are caused by decades. The impact of copper ions is dependent on the inhibition of invasive aquatic plants, many microorganisms and protozoa. The family of copper-contained chemicals is frequently used as algaecides in swimming pools. Despite the copper ions are well known as a high toxic for fish in freshwater ponds, the copper sulphate remains one of the prevalent pesticides in fish farming everywhere. High cytotoxicity and accumulation of the copper ions in the sediments require studying and calculation of the optimal dosage to use it as an antiseptic agent that should prevent the detrimental effect in various tissue types of aquatic organisms. The main depicted mechanism, which is associated with cytotoxicity is the generation of oxidative stress. Neural tissue cells are extremely susceptible to oxidative damages. Neural damaging is important cause of the CNS disfunction as well as is the critic to the organism vitality. Glial cells maintain the structure and many vital functions of neuronal cells. Glial fibrillary acidic protein (GFAP), transcriptional nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and poly(ADP-ribose) polymerase (PARP) are critic regulators in a cell response to the environment toxicity. Based on this fact, it could be applied as the boimarkers of heavy metal toxicity. In presented study, we investigated the effects of copper ions on PARP, NF-kB, and GFAP expression in the rainbow trout (Oncorhynchus mykiss) brain tissue. For 96 hours the fishes were exposed to the copper sulphate sublethal concentrations 380 µg/L, estimated as 1/4 of the LC50 value. Western blot analysis of GFAP, NF-kB and PARP was used to assess further effects in the brain tissue. The modulatory effect of copper ions on the expression of GFAP was detected in fish brain. Reciprocal changes were observed in respect with 24 hours exposure in compare to both 48 hours and 96 hours treatment. Obtained results demonstrated meaningful disturbance in the expression of transcriptional factor NF-kB in the brain of fish group exposed to copper in compare to control group. Furthermore, the time-depended effect in a range 24 – 96 hours was detected. However, the short time exposure to copper ions initiated no effect in fish group treated 24 hours while in compare to both 48 hours and 96 hours treatment. The similar changes of PARP content in the brain of fish were determined as well. It deserves to be mentioned that all of aforementioned changes of GFAP, NF-kB and PARP expression were accompanied by increasing in reactive oxygen species content. Thus, copper ions cytotoxic effect could be initiated with oxidative injury in a brain tissue. On the other hand, the observed effect of copper in the fish brain evidences the unspecific toxicity of this ion in brain tissue cells. The results showed that copper ions could induce astroglial response accompanied by modulations of NF-kB and PARP-1 expression. Obtained in presented study data suggest that copper sulphate has significant effect on astrogliosis and DNA damage in the fish brain.