4open最新文献

{"title":"In vitro assessment of stearyl triphenyl phosphonium toxicity in drug-resistant tumor cells","authors":"Shrey Shah, Miller Ouellette, G. D’souza","doi":"10.1051/fopen/2022003","DOIUrl":"https://doi.org/10.1051/fopen/2022003","url":null,"abstract":"Introduction: The triphenyl phosphonium residue is a well-documented mitochondriotropic that has been shown to improve the accumulation of biomolecules in mitochondria. Stearyl triphenyl phosphonium (STPP) modified liposomes have been shown to facilitate the selective accumulation of various biomolecules in mitochondria resulting in improved effect in-vitro and in-vivo. More recently, STPP was reported to have higher toxicity towards a drug resistant ovarian cancer cell line compare to a non-drug resistant cell line. The purpose of this study was to further investigate STPP toxicity using multiple drug resistant and non-drug resistant cell lines. Methods: STPP was incorporated into phosphatidylcholine cholesterol liposomes using the thin film hydration method. Mean particle size and zeta potential was measured using dynamic light scattering. The 5,5,6,6′-tetrachloro-1,1′,3,3′ tetraethylbenzimi-dazoylcarbocyanine iodide (JC-1) dye accumulation assay was used as an indicator of mitochondrial membrane potential in the tested cell lines. Cytotoxicity of the preparations towards different cell lines was determined using light microscopy and the CellTiter 96® AQueous One Solution Cell Proliferation assay. Results: The JC-1 accumulation assay confirmed that the drug-resistant cell lines had significantly higher dye accumulation than the non-drug resistant cell lines. Higher cytotoxicity of STPP towards drug resistant cell line was seen when incorporated into liposomes but not when dissolved in dimethyl sulfoxide (DMSO). STPP showed a comparable toxicity profile to the known oxidative phosphorylation uncoupler carbonyl cyanide p-trifluoro-methoxyphenyl hydrazone (FCCP). Discussion: Taken together, the data suggest that higher STPP toxicity in the drug-resistant cell lines is influenced by the presence of liposomal lipids and that STPP acts in a way similar to an oxidative phosphorylation uncoupler and is therefore more toxic to the drug-resistant cells that rely on a higher mitochondrial membrane potential to maintain their viability.","PeriodicalId":6841,"journal":{"name":"4open","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80632903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"War against Ukraine: Humanitarian aid and how much morality can science bear","authors":"Björn BLDM Brücher","doi":"10.1051/fopen/2022012","DOIUrl":"https://doi.org/10.1051/fopen/2022012","url":null,"abstract":"An unprovoked war has impacted Ukraine. “Humanity and peace initiatives should have top priority now” [1]. The resulting outrage by the Western world together with a global alliance has imposed economic sanctions on Russia [2]. Though moral, the efficacy of economic sanctions are known to be limited as earlier shown by an empirical cross-national, time-series data analysis of 133 countries during the period from 1970 to 2005 [3]. The TheodorBillroth-Academy with its International Consortium of Research Excellence (INCORE) have so far in solidarity with the Ukraine and with scientists and Board members of 4open realized several projects for active humanitarian aid in a very short time [1]. This included medical transports to the Ukraine which were carried out by pro bono by Veterans from Germany through the Recondo Vets MMC Germany, Military Motorcycle Club (Fig. 1) and from Austria through the Green Knights, Military Motorcycle Club, Chapter 147, Austria as they work closely with the Territorial Defense Forces (of the Ukraine) (Biqcmra nepbnopiakmyoї o,opoyb) and the International Legion of Territorial Defense of Ukraine (Ukrainian Foreign Legion) (Iynepyawioyakmybq keuioy nepbnopiakmyoї o,opoyb Erpaїyb) to ensure that transports arrive where and when needed (Figs. 2–4). Furthermore, medical refugee students from the Kharkiv National Medical University (KNMU) and the Bogomolets National Medical University (NMU) were offered cost-free living along with a German language course, academic lecture and medical internship financed by the Carl-Thiem-Klinikum (CTK) in Cottbus, Germany. The TBA and INCORE continuously encourage (and demand) that European and German-speaking universities to set an example and open their doors to Ukrainian refugee medical students during the war so that they can have the opportunity to continue their studies. Finland on March 9, 2022 provided strong leadership in this regard [4]. So far, only one German University partially opened their doors as suggested, although the primary conditions will only be achievable by a minority of students because students need a valid Test for Medical Studies (TMS) result notification. Soon, Theodor Billroth’ lectures of various themes in science, education, training for students and physicians (independent of their level and stage of career), a project which originally was planned to be realized in 2023, will be realized soon (Fig. 5). This will be cross-linked by the support of 4open and EDP Sciences as increasingly students and physicians should actively be encouraged to publish their thesis also at no cost. Thus, the proposed scientific, humanitarian and peace initiatives of our colleagues provide Ukraine with much-needed assistance. Next to humanitarian aid, it is being demanded to expel Russian culture and science from the fine arts and science. Today’s science (and medicine) is changed from a compassion-based profession into a corporate-greed driven industry why halting and expelling o","PeriodicalId":6841,"journal":{"name":"4open","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85947752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interconnection of severe obesity, gastric intestinal metaplasia, gastric cancer, bariatric surgery and the necessity of preoperative endoscopy","authors":"M. Kermansaravi, R. Valizadeh, Behnood Farazmand","doi":"10.1051/fopen/2022019","DOIUrl":"https://doi.org/10.1051/fopen/2022019","url":null,"abstract":"Obesity is a growing challenge around the globe accounting for approximately 1.7 billion adults with reduced life expectancy of 5–20 years and these patients are at greater risk for various cancers. Bariatric surgery is one efficient an approved treatment of severe obesity for losing weight and to decrease associated health complications. Besides correct indications and contraindications as well as the various risks of individual bariatric surgical procedures, many more variables influence decision-makings, such as patient’s family history of diseases, as well as individual patient-specific factors, patient and family socioeconomic and nutrition status, and professionalism of a bariatric surgical unit and the presence of intestinal metaplasia that is the replacement of columnar epithelial cells by intestinal architecture and morphology. Patients with severe obesity undergoing esophagogastroduodenoscopy (EGD) and biopsy prior to bariatric surgery may present with gastric IM because regular follow-up to early diagnosis of any subsequent pathological changes is necessary and reveals the importance of addressing interconnections between pre-existing conditions and outcomes. However, there is currently no unified recommendation about preoperative EGD before bariatric surgery. With this short review, we point out the necessary knowledge that undermines why the responsibility for a patient with severe obesity cannot be divided across various disciplines, and why we recommend that EGD always be performed preoperatively.","PeriodicalId":6841,"journal":{"name":"4open","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87206477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membraneless physiology of the living cell. The past and the present","authors":"Vladimir Vasilievich Matveev","doi":"10.1051/fopen/2022013","DOIUrl":"https://doi.org/10.1051/fopen/2022013","url":null,"abstract":"Since the 1880s, the concept of compartmentalizing through membranes has taken a firm place in cell physiology and has defined the objects, methods, and goals of physiologists’ research for decades. A huge mass of biologists know about the important role of intra-membrane pumps, channels, and lipids, and various hypotheses about the origin of life often begin with explanations about how the lipid membrane occurred, without which it is impossible to imagine the origin of a living cell. Against this background, there was a dissonance of statements that there are membraneless organelles in the cell, the functions of which are rapidly expanding under our eyes. Physically, they are similar to coacervate droplets, which from time to time were used to explain the origin of life, and now the coacervates are being more and more often discussed when describing the physics of the nucleus and cytoplasm of modern cells. However, ideas about the coacervate nature of cytoplasm/protoplasm originated in the first half of the 19th Century, when the contents of cells were likened to jelly, but this approach gradually faded into the shadows. Nevertheless, limited research in this area continued and was completed in the form of a membraneless cell physiology. Now that the focus of attention has turned to membraneless compartmentalization, it’s time to remember the past. The sorption properties of proteins are the physical basis of membraneless cell because of water adsorbed by proteins changes the physical state of any biomolecular system, from supramolecular and subcellular structures to the cell as a whole. A thermodynamic aqueous phase is formed because adsorbed water does not mix with ordinary water and, in this cause, is separated from the surrounding solution in the form of a compartment. This article discusses the fundamental physical properties of such a phase – a biophase. As it turned out, the Meyer–Overton rule, which led to the idea of a lipid membrane, also applies to membraneless condensates.","PeriodicalId":6841,"journal":{"name":"4open","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84772778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker assessment in urgent surgical pathology of the small bowel: case-control analysis of a retrospective database","authors":"Kryvoruchko Ia, T. Briukhanova, O. Nakonechna, O. S. Olefir","doi":"10.1051/fopen/2022014","DOIUrl":"https://doi.org/10.1051/fopen/2022014","url":null,"abstract":"Background: Small bowel obstruction, mesenteric thrombosis, and strangulated ventral hernia area a challenge in emergency abdominal surgery. This study aimed to evaluate biomarkers of damage to the digestive tract in patients with urgent pathology. Materials and methods: The study involved 71 patients aged 18 to 80 years who were hospitalized in the intensive care unit in the immediate postoperative period. Results: All 71 underwent emergency surgery, 27 with small bowel necrosis. Lactate level area under curve (AUC = 0.964), C-reactive protein (AUC = 0.805) and systolic blood pressure (area under curve, AUC = 0.803) on the context of Sequential Organ Failure Assessment (SOFA) score (AUC = 0.880) showed stratification of patients with complications before surgery. Small bowel necrosis patients revealed an increase in primary thiobarbituric acid (TBA) reactive products (AUC = 0.813) lipid peroxidation products, and a decrease in superoxide dismutase activity (AUC = 0.818) and catalase (AUC = 0.804). Wide variability of intestinal fatty-acid binding protein (I-FABP) from 199.8 to 2189.6 pg/mL were observed in all patients studied, with an AUC = 0.814 in small intestinal necrosis. Conclusion: Surgical pathology of the small intestine due to obstruction of various origina, mesenteric thrombosis, and strangulated ventral hernia pronounced revealed disorders of the antioxidant-prooxidant balance. This was expressed by an increase in lipid peroxidation products, and the level of TBA-reactive products, and the activities of superoxide dismutase (SOD), and catalase. Viewed against the background of an increase in I-FABP above 577 pg/mL, these variables were the most significant indicators of small intestinal necrosis.","PeriodicalId":6841,"journal":{"name":"4open","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76457287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Realtime, continuous assessment of complex-mixture protease and protease inhibitor activity","authors":"Sarah-Ellen Leonard, P. Kenis, Ray C. Perkins","doi":"10.1051/fopen/2022010","DOIUrl":"https://doi.org/10.1051/fopen/2022010","url":null,"abstract":"Recently the treatment PAXLOVID™ (nirmatrelvir co-packaged with ritonavir) was authorized for use as a treatment for COVID-19. The presumed mechanism of action of the treatment, an inhibitor of a Sars-Cov-2 “3CL” protease, continues decades-long interest in viral protease inhibition in the fight against pathogenic viruses (e.g., HIV protease inhibitors). Proteolysis assay methods vary widely, roughly bounded by interrogation of basic biochemistry and high-throughput, early-stage drug screening. Reported here are methods that provide unique and biologically relevant characterization of proteolysis and protease inhibition. A companion report provides evidence that these methods show promise for drug and basic biological discovery, especially for early detection of potential side effects. Electron spin resonance spectroscopy and spin labeling (ESRSL) of whole proteins are leveraged to monitor reactants and products of whole-protein digestion through differentiation of angular mobility of those products and reactants. These proof-of-concept data demonstrate consistency with prior art for all possible combinations of four proteases, two whole-protein substrates and three inhibitors. Thus, ESRSL is shown to uniquely and widely interrogate proteolysis of natural, whole-protein, substrates insuring the biological relevance of results.","PeriodicalId":6841,"journal":{"name":"4open","volume":"8 13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80449304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam Professor Dr. Philipp A. Schnabel (1953–2021)","authors":"B. Brücher","doi":"10.1051/fopen/2022006","DOIUrl":"https://doi.org/10.1051/fopen/2022006","url":null,"abstract":"","PeriodicalId":6841,"journal":{"name":"4open","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82303143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Logical entropy – special issue","authors":"G. Manfredi","doi":"10.1051/fopen/2022005","DOIUrl":"https://doi.org/10.1051/fopen/2022005","url":null,"abstract":"Entropy is a fundamental quantity in many areas of knowledge, from physics to information science to biology. Originally put forward in the nineteenth century for very practical purposes (to quantify the reversibility of thermodynamic cycles, hence of thermal engines), entropy was the key concept that allowed Ludwig Boltzmann to bridge the gap between the (time irreversible) macroscopic thermodynamics and the (reversible) microscopic Newtonian physics. As defined by Boltzmann, the entropy SB represents the number of microscopic states that are compatible with a given macroscopic realization:","PeriodicalId":6841,"journal":{"name":"4open","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86407630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum logical entropy: fundamentals and general properties","authors":"B. Tamir, Ismael Lucas De Paiva, Zohar Schwartzman-Nowik, E. Cohen","doi":"10.1051/fopen/2021005","DOIUrl":"https://doi.org/10.1051/fopen/2021005","url":null,"abstract":"Logical entropy gives a measure, in the sense of measure theory, of the distinctions of a given partition of a set, an idea that can be naturally generalized to classical probability distributions. Here, we analyze how this fundamental concept and other related definitions can be applied to the study of quantum systems with the use of quantum logical entropy. Moreover, we prove several properties of this entropy for generic density matrices that may be relevant to various areas of quantum mechanics and quantum information. Furthermore, we extend the notion of quantum logical entropy to post-selected systems.","PeriodicalId":6841,"journal":{"name":"4open","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84454504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent developments in mitochondrial medicine (Part 1)","authors":"V. Weissig, M. Edeas","doi":"10.1051/FOPEN/2021002","DOIUrl":"https://doi.org/10.1051/FOPEN/2021002","url":null,"abstract":"Research into elucidating structure and function of mitochondria has been quite steady between the time of discovery during the end of the 19th century until towards the late 1980’s. During the 1990s there was talk about a “comeback” of this organelle reflecting a widely revitalized interest into mitochondrial research which was based on two major discoveries made during that time. The first was the etiological association between human diseases and mitochondrial DNA mutations, while the second revealed the crucial function of mitochondria during apoptosis. The March 5th, 1999 issue of Science even featured a textbook image of a mitochondrion on its front cover and was entirely dedicated to this organelle. Whilst the term “comeback” might have been appropriate to describe the general excitement surrounding the new mitochondrial discoveries made during the 1990s, a term for describing the progress made in mitochondrial research during the last two decades is difficult to find. Between 2000 and 2020 the number of publications on mitochondria has skyrocketed. It is now widely accepted that there hardly exists any human disease for which either the etiology or pathogenesis does not seem to be associated with mitochondrial malfunction. In this review we will discuss and follow several lines of mitochondrial research from their early beginnings up to the present. We hope to be able to convince the reader of what we expressed about a decade ago, that the future of medicine will come through mitochondria.","PeriodicalId":6841,"journal":{"name":"4open","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90957407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}