TY - GEN A1 - Kaiser, Ulrich A1 - Vehling-Kaiser, Ursula A1 - Kück, Fabian A1 - Gilanschah, Mia A1 - Jung, Friedrich A1 - Jung, Ernst Michael T1 - Super-resolution contrast-enhanced ultrasound examination down to the microvasculature enables quantitative analysis of liver lesions : first results T2 - Life N2 - This article investigates the first use of dynamic microvascularization of liver lesions in clinical evaluation using real-time super-resolution contrast-enhanced ultrasound (SR CEUS). A retrospective analysis of SR CEUS examinations of liver lesions was performed. All examinations were conducted using an SC7-1U convex probe after the bolus injection of the ultrasound contrast agent. Digital cine loops were stored for independent evaluation. The evaluation was performed with respect to parallel measuring lines (the diameter corresponded to the capillary density) in the area of the reference lesion, liver tissue, and liver capsule using statistical analysis. In total, 65 patients (female n = 28; male n = 37; average age 57.8 ± 17.2 years) were evaluated. The examined liver lesions were mostly benign masses ( n = 46). Mild liver fibrosis (stage F1) was present in most cases ( n = 35). The lesions examined were located at an average tissue depth of 6.07 ± 2.47 cm. The highest number of lesion measurements was observed in the malignant lesion group. Significant differences in the measurements were found when comparing benign lesions with the capillary region ( p < 0.001) and normal liver tissue ( p < 0.01). The use of SR CEUS opens up new possibilities for the quantification of neovascularization, assessment of microvascular changes, and evaluation of the follow-up of intrahepatic interventions. KW - contrast agent KW - ultrasonography KW - liver KW - intervention KW - microvascularization Y1 - 2025 U6 - https://doi.org/10.3390/life15070991 SN - 2075-1729 VL - 15 IS - 7 SP - 1 EP - 16 PB - MDPI CY - Basel ER - TY - GEN A1 - Braune, Steffen A1 - Jung, Conrad G. H. A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Arthrospira platensis as protein-rich source for human nutrition T2 - Life N2 - The continuing growth of the world’s population, combined with climate change, poses a growing challenge to ensuring food security in the 21st century. Animal protein, e.g., from beef, is a particularly rich source of protein, but there is by no means enough arable land on earth to transfer the animal meat-rich nutritional style of the early industrialized countries to the global South. A hitherto largely neglected option for the production of proteins is the cultivation of microalgae and cyanobacteria, which already have a long history of use as a human or animal food for their nutritional and environmental merits. In particular, Limnospira platensis (Spirulina and formerly Arthrospira platensis)—a filamentous cyanobacterium—is considered the “food of the future” since it is a viable source of vegan protein. In this manuscript, we review the scientific literature as well as national and intergovernmental agency statements regarding the quality and quantity of AP-based proteins. The content of AP protein is d KW - Arthrospira platensis KW - Limnospira platensis KW - Protein quality KW - Protein quantity Y1 - 2025 U6 - https://doi.org/10.3390/life15121789 SN - 2075-1729 VL - 15 IS - 12 SP - 1 EP - 15 PB - MDPI CY - Basel ER - TY - GEN A1 - Sieber, Irmgard Maria A1 - Jung, Friedrich A1 - Jung, Ernst Michael T1 - High-resolution contrast-enhanced ultrasound with SRCEUS for assessing the intrahepatic microvasculature and shunts in patients with hereditary haemorrhagic teleangiectasia (Osler’s disease) T2 - Life N2 - The aim of this retrospective clinical pilot study is to evaluate multiparametric ultrasound liver parenchyma assessments in the diagnosis of Osler’s disease, and to detect micro-shunts using SRCEUS with quantifications at the capillary level. Material/Method: All examinations were performed by an experienced examiner with a multi-frequency probe on a high-resolution matrix ultrasound device (SC 7-1U), convex probe (Mindray A 20), and were stored digitally in the PACS system. Vascular ultrasound was performed using colour-coded Doppler ultrasound (CCDS) and ultrasound microangiography (UMA). The recent M-Ref tool was utilised for the purpose of liver tissue characterisation, encompassing the domains of shear wave elastography, fat evaluation, and viscosity. Dynamic CEUS, HiFR CEUS, and SR CEUS were performed after the intravenous bolus injection of 1–2.4 mL of ultrasound contrast agent (SonoVue®). Measurements of SR CEUS capillary changes were performed independently by PACS-stored digital cine loops up to 5 s. Results: In the context of angiomas or haemangiomas, the initial contrast enhancement of echogenic or almost echogenic foci within 25 s without late wash-out was observed in 5/10 cases. In the evaluation of microvasculature, the presence of capsule-proximal shunts in Osler’s disease was observed, resulting in the identification of increased numbers of dilated capillaries within both peripheral and central shunts. In the control group, general liver tissue changes (20 cases) were observed in instances of inflammation (3/20 cases), peripherally in 4/20 cases with micro-shunts in altered parenchyma. In the context of multiparametric ultrasound, 16 out of 30 cases exhibited elevated fibrosis values, with a maximum recorded as high as 1.7 m/s, and in 13 out of 30 cases, there was an increase in fat values up to 0.65 dB/cm/MHz, indicative of moderate steatosis. Additionally, in seven cases, there was an increase in viscosity values up to 2.7 Pa·s, suggesting reactive changes. Conclusions: Recent advancements in medical imaging technology, specifically SR CEUS contrast ultrasound imaging, have led to the development of novel diagnostic tools that facilitate the evaluation of tissue and haemodynamic changes, in addition to capillary alterations, associated with Osler’s disease. KW - Osler’s disease KW - Shunts; Superresolution CEUS (SR-CEUS) KW - Multiparametric tissue imaging (M-Ref) Y1 - 2025 U6 - https://doi.org/10.3390/life15101631 SN - 2075-1729 VL - 15 IS - 10 SP - 1 EP - 15 PB - MDPI AG CY - Basel ER - TY - GEN A1 - Dropco, Ivor A1 - Kaiser, Ulrich A1 - Jung, Friedrich A1 - Danihel, Ľudivít A1 - Schlitt, Hans J A1 - Stroszczynski, Christian A1 - Herr, Wolfgang A1 - Brunner, Stefan M A1 - Jung, Ernst Michael T1 - Intraoperative contrast-enhanced ultrasound (CEUS) with time intensity curve (TIC) analysis for better assessment of liver tumor margins T1 - Intraoperative Kontrastmittelsonografie (CEUS) mit Time Intensitiy Curve (TIC)-Analyse zur Beurteilung von Lebertumorgrenzen T2 - RöFo : Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren N2 - AbstractThe purpose of this study was to conduct an intraoperative evaluation of focal liver lesions using time intensity curve (TIC) analysis of contrast-enhanced ultrasound (CEUS) to better assess liver tumor margins.This study included 28 patients (21 men 75%, 7 women 25%) with malignant liver lesions (cholangiocellular carcinoma (CCC), n = 9; hepatocellular carcinoma (HCC), n = 6; hepatic metastases (HepMET), n = 13). A B-mode scan, color-coded Doppler sonography, and CEUS were performed intraoperatively to analyze the focal lesions. The generated parametric images were based on continuous cine loops, acquired with a multifrequency T-probe (6–9 MHz), from the early arterial phase (0–15 seconds) to the portal venous phase (1 minute), generated by integrated perfusion software. Analyses of the CEUS loops were performed using TICs with respect to time-to-peak (TTP) and area under the curve (AUC). Perfusion analysis was performed in the center and periphery of the tumor as well as in healthy liver tissue. All tumor lesions were evaluated histopathologically to verify the diagnosis.Sufficient image quality was achieved in all cases using CEUS for TIC analysis. A comparison of all groups showed a clear difference compared with the center, margin, and healthy liver tissue in the measured parameters of TTP and AUC (p = 0.035 and p = 0.045, respectively). In detail, differences were observed in the CCC group (TTP: p = 0.025) and in the HepMET group (TTP: p = 0.009), particularly in the peripheral areas (strong arterial flooding with a rapid increase in the flooding curve), with equally clear tumor edge representation compared with healthy liver tissue, as shown by the AUC analysis (CCC AUC: p = 0.032 and HepMET AUC: p = 0.029). In patients with HCC, the perfusion pattern (starting from the center) showed the center to be more clearly distinguishable from the edge with significant TTP and AUC (p = 0.035 and p = 0.038).Intraoperative TIC analysis of malignant liver tumors is an important diagnostic tool for better highlighting liver tumor margins during surgery. Y1 - 2025 U6 - https://doi.org/10.1055/a-2600-7229 SN - 1438-9029 VL - 6 IS - 2 SP - 430 EP - 446 PB - Georg Thieme Verlag KG CY - Stuttgart ER - TY - GEN A1 - Schulz, Christian A1 - Stegen, Sarah A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner ED - Lamb, David ED - Syed, Khajamohiddin T1 - Mono-CYP CHO model : a recombinant Chinese hamster ovary cell platform for investigating CYP-specific tamoxifen metabolism T2 - International journal of molecular sciences N2 - The metabolism of drugs and foreign substances in humans typically involves multiple enzymatic steps, particularly in phase-1 biotransformation in the liver, where various cytochrome P450 monooxygenases (CYPs) play crucial roles. This complexity can lead to a wide range of metabolites. Understanding the contributions of individual CYPs and their interactions within these intricate enzyme cascades can be challenging. We recently developed an in vitro biotransformation platform employing various Chinese Hamster Ovarian (CHO) cell clones. These clones express human cytochrome P450 oxidoreductase (CPR), and each is defined by a specific human CYP enzyme expression, thus exhibiting no detectable endogenous CYP enzyme activity (mono-CYP CHO platform). In this study, we investigated whether the mono-CYP CHO platform is a suitable tool for modeling complex drug metabolization reactions in vitro. Tamoxifen (TAM) was selected as a model substance due to its role as a prodrug widely used in breast cancer therapy, where its main active metabolite, endoxifen, arises from a two-step metabolism primarily involving the CYP system. Specifically, the combined activity of CYP3A4 and CYP2D6 is believed to be essential for efficient endoxifen production. However, the physiological metabolization pathway of TAM is more complex and interconnected, and the reasons for TAM’s therapeutic success and variability among patients are not yet fully understood. Analogous to our recently introduced mono-CYP3A4 CHO cells, we generated a CHO cell line expressing human CPR and CYP2D6, including analysis of CYP2D6 expression and specific activity. Comparative studies on the metabolization of TAM were performed with both mono-CYP CHO models individually and in co-culture with intact cells as well as with isolated microsomes. Supernatants were analyzed by HPLC to calculate individual CYP activity for each metabolite. All the picked mono-CYP2D6 clones expressed similar CYP2D6 protein amounts but showed different enzyme activities. Mono-CYP2D6 clone 18 was selected as the most suitable for TAM metabolization based on microsomal activity assays. TAM conversion with mono-CYP2D6 and -3A4 clones, as well as the combination of both, resulted in the formation of the expected main metabolites. Mono-CYP2D6 cells and microsomes produced the highest detected amounts of 4-hydroxytamoxifen and endoxifen, along with N -desmethyltamoxifen and small amounts of N , N -didesmethyltamoxifen. N -desmethyltamoxifen was the only TAM metabolite detected in notable quantities in mono-CYP3A4, while 4-hydroxytamoxifen and endoxifen were present only in trace amounts. In CYP2D6/3A4 co-culture and equal mixtures of both CYP microsomes, all metabolites were detected at concentrations around 50% of those in individual clones, indicating no significant synergistic effects. In conclusion, our mono-CYP CHO model confirmed the essential role of CYP2D6 in synthesizing the active TAM metabolite endoxifen and indicated that CYP2D6 is also involved in producing the by-metabolite N , N -didesmethyltamoxifen. The differences in metabolite spectra between the two mono-CYP models highlight the CYP specificity and sensitivity of our in vitro system. KW - Chinese hamster ovary cells KW - Mono-CYP CHO KW - Liver KW - Phase-1 biotransformation KW - Cytochrome P450 monooxygenase KW - CYP2D6 KW - Tamoxifen KW - Endoxifen KW - DDM-TAM Y1 - 2025 U6 - https://doi.org/10.3390/ijms26093992 SN - 1422-0067 VL - 26 IS - 9 SP - 1 EP - 24 PB - MDPI CY - Basel ER - TY - GEN A1 - Rampling, Mike A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Prantl, Lukas T1 - In memory of Prof. Dr. Bo Sandhagen T2 - Clinical hemorheology and microcirculation Y1 - 2025 U6 - https://doi.org/10.1177/13860291251343775 SN - 1386-0291 VL - 90 IS - 2 SP - 49 EP - 49 PB - SAGE Publications CY - London ER - TY - GEN A1 - Jung, Friedrich A1 - Prantl, Lukas A1 - Rampling, Mike A1 - Connes, Philippe T1 - Obituary for Giles Roy Cokelet T2 - Clinical hemorheology and microcirculation Y1 - 2025 U6 - https://doi.org/10.1177/13860291251343774 SN - 1386-0291 VL - 90 IS - 2 SP - 50 EP - 50 PB - SAGE Publications CY - London ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Lehmann, Christian T1 - A.L. Copley Best Paper Prize 2023 T2 - Clinical hemorheology and microcirculation Y1 - 2025 U6 - https://doi.org/10.1177/13860291251331151 SN - 1386-0291 VL - 89 IS - 4 SP - 315 EP - 315 PB - SAGE Publications CY - London ER -