@misc{LemmKoehlerWodtkeetal., author = {Lemm, Sandy and K{\"o}hler, Susanne and Wodtke, Robert and Jung, Friedrich and K{\"u}pper, Jan-Heiner and Pietzsch, Jens and Laube, Markus}, title = {Enabling insights into the cytochrome P450 isoform specific metabolism of radiotracers by CYP overexpressing hepatoblastoma cell lines}, series = {Nuclear Medicine and Biology}, journal = {Nuclear Medicine and Biology}, number = {108-109, Supplement }, issn = {1872-9614}, pages = {S66 -- S67}, language = {en} } @misc{BuchmuellerEngePetersetal., author = {Buchmueller, Julia and Enge, Anne-Margarethe and Peters, Antonia and Ebmeyer, Johanna and K{\"u}pper, Jan-Heiner and Sch{\"a}fer, Bernd and Br{\"a}uning, Albert and Hessel-Pras, Stefanie}, title = {The chemical structure impairs the intensity of genotoxic effects promoted by 1,2-unsaturated pyrrolizidine alkaloids in vitro}, series = {Food and Chemical Toxicology}, volume = {Vol. 164}, journal = {Food and Chemical Toxicology}, issn = {1873-6351}, doi = {10.1016/j.fct.2022.113049}, language = {en} } @misc{KnauerSchulzZemellaetal., author = {Knauer, Jan Felix and Schulz, Christian and Zemella, Anne and W{\"u}stenhagen, Doreen A. and Walter, Ruben Magnus and K{\"u}pper, Jan-Heiner and Kubick, Stefan}, title = {Synthesis of mono Cytochrome P450 in a modified CHO-CPR cell-free protein production platform}, series = {Scientific Reports}, volume = {14}, journal = {Scientific Reports}, issn = {2045-2322}, doi = {10.1038/s41598-024-51781-6}, pages = {14}, abstract = {AbstractCytochromes P450 (CYPs) are a group of monooxygenases that can be found in almost all kinds of organisms. For CYPs to receive electrons from co-substrate NADPH, the activity of NADPH-Cytochrome-P450-oxidoreductase (CPR) is required as well. In humans, CYPs are an integral part of liver-based phase-1 biotransformation, which is essential for the metabolization of multiple xenobiotics and drugs. Consequently, CYPs are important players during drug development and therefore these enzymes are implemented in diverse screening applications. For these applications it is usually advantageous to use mono CYP microsomes containing only the CYP of interest. The generation of mono-CYP containing mammalian cells and vesicles is difficult since endogenous CYPs are present in many cell types that contain the necessary co-factors. By obtaining translationally active lysates from a modified CHO-CPR cell line, it is now possible to generate mono CYPs in a cell-free protein synthesis process in a straightforward manner. As a proof of principle, the synthesis of active human CYPs from three different CYP450 gene families (CYP1A2, CYP2B6 and CYP3A4), which are of outstanding interest in industry and academia was demonstrated. Luciferase based activity assays confirm the activity of the produced CYPs and enable the individual adaptation of the synthesis process for efficient cell-free enzyme production. Furthermore, they allow for substrate and inhibitor screenings not only for wild-type CYPs but also for mutants and further CYP isoforms and variants. As an example, the turnover of selected CYP substrates by cell-free synthesized CYPs was demonstrated via an indirect luciferase assay-based screening setup.}, language = {en} } @misc{JungConnes, author = {Jung, Friedrich and Connes, Philippe}, title = {Morphology and Function of Red Blood Cells in COVID-19 Patients: Current Overview 2023}, series = {Life}, volume = {14}, journal = {Life}, number = {4}, issn = {2075-1729}, doi = {10.3390/life14040460}, abstract = {In severe cases, SARS-CoV-2 infection leads to severe respiratory failure. Although angiotensin-converting enzyme 2 (ACE2) receptors are not expressed in red blood cells, SARS-CoV-2 can interact with red blood cells (RBCs) via several receptors or auxiliary membrane proteins. Recent data show that viral infection causes significant damage to the RBCs, altering their morphology, deformability, and aggregability. Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation, as has been described to occur in COVID-19 patients. In addition, many patients also develop systemic endotheliitis associated with generalized coagulopathy. This manifests itself clinically as obstructive microthrombi in the area of the medium and smallest vessels, which can affect all internal organs. It is thought that such changes in the RBCs may contribute to the microangiopathy/microthrombosis associated with COVID-19 and may result in impaired capillary blood flow and tissue oxygenation.}, language = {en} } @misc{JungKaiserHerretal., author = {Jung, E.M. and Kaiser, U. and Herr, W. and Stroszczynski, C. and Jung, F.}, title = {Novel high-resolution contrast agent ultrasound techniques HiFR CEUS and SR CEUSin combination with shear wave elastography, fat assessment and viscosity of liver parenchymal changes and tumors}, series = {Clinical Hemorheology and Microcirculation}, volume = {86 (2024)}, journal = {Clinical Hemorheology and Microcirculation}, doi = {10.3233/CH-249103}, pages = {263 -- 273}, abstract = {Abstract. BACKGROUND: The continuous development of ultrasound techniques increasingly enables better description and visu alization of unclear lesions. New ultrasound systems must be evaluated with regard to all these diagnostic possibilities. METHODS:Amultifrequency C1-7 convex probe (SC7-1M) with the new high-end system Resona A20 Series was used moderntechnologies, includingHiFRCEUS, SRCEUSandmultimodaltissueimaging withs hearwaveelastography(SWE), fat evaluation and viscosity measurements (M-Ref) were applied. RESULTS:Ofn=70(meanvalue 48,3 years±20,3 years, range 18-84 years) cases examined, a definitive diagnosis could be made in n=67 cases, confirmed by reference imaging and/or follow-up. Of these, n=22 cases were malignant changes (HCC (hepatocellular carcinoma) n=9, CCC (cholangiocellular carcinoma) n=3, metastases of colorectal carcinomas or recurrences of HCC n=10). In all 12 cases of HCC or CCC, the elastography measurements using the shear wave technique (with values >2m/s to 3.7m/s) showed mean values of 2.3±0.31m/s and a degree of fibrosis of F2 to F4. In n=14 cases, changes in the fat measurement (range 0.51 to 0.72dB/cm/MHz, mean values 0.58±0.12dB/cm/MHz) in the sense of proportional fatty changes in the liver were detected. In the 4 cases of localized fat distribution disorders, the values were >0.7dB/cm/MHz in the sense of significant fatty deposits in the remaining liver tissue. Relevant changes in the viscosity measurements with values >1.8kPa were found in n=31 cases, in n=5 cases of cystic lesions with partially sclerosing cholangitis, in n=13 cases of malignant lesions and in n=9 cases post-interventionally, but also in n=4 cases of benign foci with additional systemic inflammation. CONCLUSIONS:The results are promising and show a new quality of ultrasound-based liver diagnostics. However, there is a need for further investigations with regard to the individual aspects, preferably on a multi-center basis.}, language = {en} } @misc{JavakhishviliSanikidzeMardaleishvilietal., author = {Javakhishvili, I and Sanikidze, T and Mardaleishvili, K and Momtselidze, N and Urdulashvili, T and Mantskava, M and Prantl, L and Jung, F}, title = {Finding possible diagnostic markers for differentiating benign and malignant thyroid tumors on example investigate of rheological properties}, series = {Clinical Hemorheology and Microcirculation}, volume = {87 (2024)}, journal = {Clinical Hemorheology and Microcirculation}, number = {4}, doi = {10.3233/CH-249102}, pages = {515 -- 526}, abstract = {BACKGROUND: The functioning of the thyroid gland is a multi-component process that in some conditions may undergo alterations. The thyroid gland is part of the endocrine system that produces the iodine-containing hormones thyroxine and triiodothyronine. Thyroid hormones, control metabolism and energy, growth processes, maturation of tissues and organs, regulation of blood flow, and, therefore, providing vital functions of the body. The role of thyroid hormones in the regulation of blood flow is determined by the intensity of their production and the quantity in the blood. Presumably, in case of oncological and non-oncological diseases of the thyroid gland, the fluidity of the blood, which depends on the rheological properties, will be different. OBJECTIVE: Our aim was investigating rheological characteristics for studying of changes of rheology in patients with thyrotoxicosis, with benign tumor pathology of the thyroid gland, with thyroid cancer and finding possible diagnostic markers for differentiating benign and malignant thyroid tumors METHODS: In this regard, we examined, using modern methods accepted in clinical practice, a standard list of recommended diagnostic tests in the group of patients (thyrotoxicosis: n = 25; benign tumor: n = 47), thyroid cancer: n = 35) and control group (n = 15), and with new original methods, parameters that describe the rheological properties of the blood, such as blood rheological index, volume, thickness, surface area of erythrocytes, erythrocyte aggregation index, deformation index, plasma viscosity, hematocrits. RESULTS: Against the background of relative changes in the studied values, it is necessary to pay attention to the fact that erythrocyte aggregation in patients with a benign form and control, as well as in patients with a malignant form and control, differ significantly from each other, in addition, there is a significant difference between aggregation in the group of patients with benign and control aggregation. malignant forms of the disease. It is significant that aggregability differs in patients with thyrotoxicosis and in controls. This indicates that erythrocyte aggregation is particularly informative. The blood rheological index most clearly demonstrated the difference between benign and malignant forms of the disease. Significantly changed compared to control in various forms of thyroid diseases. CONCLUSION: Additional diagnostic markers for differentiating benign and malignant thyroid tumors may be consideredeerythrocyte aggregation index and blood rheological index.}, language = {en} } @misc{BagherzadehRahmaniMarzettiKaramietal., author = {Bagherzadeh-Rahmani, B and Marzetti, E and Karami, E and Campbell, BI and Fakourian, A and Haghighi, AH and Mousavi, SH and Heinrich, KM and Brazzi, L and Jung, F and Baker, JS and Patel, DI}, title = {Tirzepatide and exercise training in obesity}, series = {Clinical Hemorheology and Microcirculation}, volume = {87 (2024)}, journal = {Clinical Hemorheology and Microcirculation}, number = {4}, doi = {10.3233/CH-242134}, pages = {465 -- 480}, abstract = {OBJECTIVES: The purpose of this study was to investigate the effects of 6 weeks of resistance training (RT) combined with aerobic training (AT) and Tirzepatide supplementation on lipid profiles, insulin resistance, anthropometric characteristics and physical fitness in prediabetic obese soldiers. METHODS: 61 obese men were randomly divided into six groups: Placebo; Tirzepatide 5 mg (T5); Tirzepatide 2.5 mg (T2.5); Hypertrophy, Strength, Power-Circuit Training+Placebo (Ex+P); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 5 mg (Ex+T5); Hypertrophy, Strength, Power-Circuit Training+Tirzepatide 2.5 mg (Ex+T2.5). All training groups performed aerobic training (AT) after resistance training. Subjects trained for six weeks, three sessions per week. Before and after the intervention period, the participants were evaluated for anthropometric measures, body composition [body weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM)], cardiorespiratory fitness (VO2max), and muscle strength (chest press 1RM and leg press 1RM). Blood biochemistry evaluations included triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), insulin level and insulin resistance (HOMA-IR). To evaluate the differences between the groups, ANCOVA statistical method was used along with Bonferroni's post hoc test, and the significance level was P < 0.05. RESULTS: Body weight, BMI, WC, FM, FBG, LDL-C, TC, TG and HOMA-IR were significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. WHR significantly decreased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo group. HDL-C, chest press and leg press significantly increased in Ex+P, Ex+T5 and Ex+T2.5 groups compared to Placebo, T5 and T2.5 groups. VO2max significantly increased and insulin significantly decreased in Ex+P group compared to Placebo, T5 and T2.5 groups. FM, FBG and TG were significantly decreased in both the T2.5 and T5 groups compared to Placebo group. HOMA-IR, LDL-C and TC significantly decreased in the T5 group compared to Placebo group. Also, leg press significantly increased in Ex+P group compared to all other groups. CONCLUSIONS: Performing six weeks of combined resistance and aerobic training in the form of RT+AT alone is more effective than the simultaneous use of Tirzepatide on cardiorespiratory fitness, strength, and modulating insulin levels. Taking Tirzepatide in doses of 5 mg and 2.5 mg in combination with exercise training did not have a significant advantage over exercise training alone. Finally, taking Tirzepatide in doses of 5 mg or 2.5 mg in combination with exercise training is not significantly superior to each other.}, language = {en} } @misc{RinkKuenzelStrosczynskietal., author = {Rink, M and K{\"u}nzel, J and Strosczynski, C and Jung, F and Jung, EM}, title = {Smart scanning: automatic detection of superficially located lymph nodes using ultrasound - initial results}, series = {Fortschr R{\"o}ntgenstr Fortschritte auf dem Gebiet der R{\"o}ntgenstrahlen und der bildgebenden Verfahren}, volume = {2024}, journal = {Fortschr R{\"o}ntgenstr Fortschritte auf dem Gebiet der R{\"o}ntgenstrahlen und der bildgebenden Verfahren}, doi = {10.1055/a-2331-0951}, pages = {1 -- 7}, abstract = {Purpose Over the last few years, there has been an increasing focus on integrating artificial intelligence (AI) into existing imaging systems. This also applies to ultrasound. There are already applications for thyroid and breast lesions that enable AI-assisted sonography directly on the device. However, this is not yet the case for lymph nodes. Materials and Methods The aim was to test whether already established programs for AI-assisted sonography of breast lesions and thyroid nodules are also suitable for identifying and measuring superficial lymph nodes. For this purpose, the two programs were used as a supplement to routine ultrasound examinations of superficial lymph nodes. The accuracy of detection by AI was then evaluated using a previously defined score. If available, a comparison was made with cross-sectional imaging. Results The programs that were used are able to adequately detect lymph nodes in the majority of cases (78.6\%). Problems were caused in particular by a high proportion of echo-rich fat, blurred differentiation from the surrounding tissues and the occurrence of lymph node conglomerates. The available cross-sectional images did not contradict the classification of the lesion as a lymph node in any case. Conclusion In the majority of cases, the tested programs are already able to detect and measure superficial lymph nodes. Further improvement can be expected through specific training of the software. Further developments and studies are required to assess risk of malignancy.}, language = {en} } @misc{GogilashviliTsinamdzgvrishviliMomtselidzeetal., author = {Gogilashvili, N and Tsinamdzgvrishvili, B and Momtselidze, N and Jung, F and Prantl, L and Urdulashvili, T and Mantskava, M}, title = {Study of some components of the influence and formation of blood flow in patients with "slow flow"}, series = {Clinical Hemorheology and Microcirculation}, volume = {88 (2024)}, journal = {Clinical Hemorheology and Microcirculation}, number = {3}, doi = {10.3233/CH-249104}, pages = {325 -- 336}, abstract = {BACKGROUND: "Slow flow" is one very important concept in modern fundamental and clinical biomedicine. Slow coronary flow is indicative of delayed filling of the terminal coronary artery vessels, occurring in the absence of significant coronary stenosis. This group patient of patients exhibits a high incidence of disability and represents a significant financial and material burden for the state and the healthcare system in general. OBJECTIVE: The primary objective of our study was to examine patients with slow coronary flow. METHODS: We studied the standard parameters recommended by the international health care system (electrocardiography (by Medica QRS-12, Germany), through the electrical activity of a patient's heart by the electrical impulses (beating) of the heart; HC1(Germany); coagulogramma by Coatron M1 (Germany), troponin by AQT 90 (Germany); general blood test we used automatic human counting device HC1(Germany). Also, we investigate the original parameters (non-standard parameters, which we use in this pilot study) that we were first studied for this diagnosis and non-standard parameters. RESULTS: A general blood test showed that patients with slow flow had a higher blood leukocyte count than the control group, but the amount of hemoglobin was normal, the hematocrit was much higher than in the control group, and the platelet count was close to the lower limit of clinical standards. We obtained details of blood flow by coagulation situation, such as prothrombin time, prothrombin index, international normalized ratio, activated partial thromboplastin time, thrombin time, fibrinogen, and rheological properties such as index of erythrocyte aggregability, index of erythrocyte deformability, plasma viscosity, in silico blood rheological index. CONCLUSSION: Blood flow can be considered as a superposition of vortices with similar frequencies and wave vectors that change after bifurcations or other obstacles in the vascular network. These factors together determine the conditions for structuring the flow of moving blood. Disruption or alteration of these factors results in slow flow. It has been found that the speed of blood flow in the coronary arteries depends on changes in the number and function of red blood cells. Slow flow is directly influenced by the aggregation and deformation of red blood cells, their number, and plasma viscosity. Consequently, the rheological status plays a crucial role in determining blood flow and its velocity.}, language = {en} } @misc{KordiSaydiAzimietal., author = {Kordi, N and Saydi, A and Azimi, M and Mazdarani, F and Gadruni, K and Jung, F and Karami, S}, title = {Cuproptosis and physical training}, series = {Clinical Hemorheology and Microcirculation}, volume = {88 (2024)}, journal = {Clinical Hemorheology and Microcirculation}, number = {3}, doi = {10.3233/CH-242329}, pages = {337 -- 350}, abstract = {Copper is an essential element in the human body, involved in many physiological and metabolic functions, including coagulation, oxidative metabolism, and hormone production. The maintenance of copper homeostasis within cells is a complex procedure that is intrinsically controlled by a multitude of intricate mechanisms. Disorders of copper homeostasis encompass a wide range of pathological conditions, including degenerative neurological diseases, metabolic disorders, cardio-cerebrovascular diseases, and tumors. Cuproptosis, a recently identified non-apoptotic mode of cell death mode, is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis represents a novel form of cell death distinct from the previously described modes, including apoptosis, necrosis, pyroptosis, and ferroptosis. Excess copper has been shown to induce cuproptosis by stimulating protein toxic stress responses via copper-dependent abnormal oligomerization of lipoylation proteins within the tricarboxyli}, language = {en} }