المؤلفون: Preetam Guha Ray, Debasis Maity, Jinbo Huang, Henryk Zulewski, Martin Fussenegger

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023)

مصطلحات موضوعية: Science

الوصف: Abstract Precision medicine requires smart, ultrasensitive, real-time profiling of bio-analytes using interconnected miniaturized devices to achieve individually optimized healthcare. Here, we report a versatile bioelectronic interface (VIBE) that senses signaling-cascade-guided receptor-ligand interactions via an electronic interface. We show that VIBE offers a low detection limit down to sub-nanomolar range characterised by an output current that decreases significantly, leading to precise profiling of these peptide hormones throughout the physiologically relevant concentration ranges. In a proof-of-concept application, we demonstrate that the VIBE platform differentiates insulin and GLP-1 levels in serum samples of wild-type mice from type-1 and type-2 diabetic mice. Evaluation of human serum samples shows that the bioelectronic device can differentiate between samples from different individuals and report differences in their metabolic states. As the target analyte can be changed simply by introducing engineered cells overexpressing the appropriate receptor, the VIBE interface has many potential applications for point-of-care diagnostics and personalized medicine via the internet of things.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/ceb2ffa8b9c649c28caa56a7555fd226

المؤلفون: Anna-Elisabeth Minder, Xiaoye Schneider-Yin, Henryk Zulewski, Christoph E. Minder, Elisabeth I. Minder

المصدر: Life, Vol 13, Iss 4, p 1066 (2023)

مصطلحات موضوعية: Erythropoietic protoporphyria, liver damage, afamelanotide, dose effect, Science

الوصف: In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. Methods: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. Results: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). Conclusions: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/2075-1729/13/4/1066; https://doaj.org/toc/2075-1729

URL الوصول: https://doaj.org/article/841d190ad35344b985b32d6f0a91a8f8

المؤلفون: Henryk Zulewski, Luca Giovanella, Stefan Bilz, Emanuel Christ, Andreas Haldemann, Hans Steinert, Sabine Weidner, Daniel Oertli, Frédéric Triponez, Thomas Clerici, Anna Minder, Matthias Dettmer, Paul Komminoth

المصدر: Swiss Medical Weekly, Vol 149, Iss 0304 (2019)

مصطلحات موضوعية: consensus guidelines, low risk papillary thyroid cancer, radioiodine treatment, thyroid surgery, Medicine

وصف الملف: electronic resource

Relation: https://www.smw.ch/index.php/smw/article/view/2571; https://doaj.org/toc/1424-3997

URL الوصول: https://doaj.org/article/edb453ee9cd5459a9fb5c0b6fd756be7

المؤلفون: Pratik Saxena, Boon Chin Heng, Peng Bai, Marc Folcher, Henryk Zulewski, Martin Fussenegger

المصدر: Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016)

مصطلحات موضوعية: Science

الوصف: Synthetic biology offers the potential for the design and implementation of rationally designed, complex genetic programmes. Here the authors design a genetic network to trigger the differentiation of patient derived IPSCs into beta-like cells.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/066ccf7797a74348a01c165392480612

المؤلفون: Eric Grouzmann, Oliver Tschopp, Frédéric Triponez, Maurice Matter, Stefan Bilz, Michael Brändle, Tilman Drechser, Sarah Sigrist, Henryk Zulewski, Christoph Henzen, Stefan Fischli, Karim Abid

المصدر: PLoS ONE, Vol 10, Iss 5, p e0125426 (2015)

مصطلحات موضوعية: Medicine, Science

الوصف: Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing neuroendocrine tumors that arise respectively inside or outside the adrenal medulla. Several reports have shown that adrenal glucocorticoids (GC) play an important regulatory role on the genes encoding the main enzymes involved in catecholamine (CAT) synthesis i.e. tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). To assess the influence of tumor location on CAT metabolism, 66 tissue samples (53 PHEO, 13 PGL) and 73 plasma samples (50 PHEO, 23 PGL) were studied. Western blot and qPCR were performed for TH, DBH and PNMT expression. We found a significantly lower intra-tumoral concentration of CAT and metanephrines (MNs) in PGL along with a downregulation of TH and PNMT at both mRNA and protein level compared with PHEO. However, when PHEO were partitioned into noradrenergic (NorAd) and mixed tumors based on an intra-tumoral CAT ratio (NE/E >90%), PGL and NorAd PHEO sustained similar TH, DBH and PNMT gene and protein expression. CAT concentration and composition were also similar between NorAd PHEO and PGL, excluding the use of CAT or MNs to discriminate between PGL and PHEO on the basis of biochemical tests. We observed an increase of TH mRNA concentration without correlation with TH protein expression in primary cell culture of PHEO and PGL incubated with dexamethasone during 24 hours; no changes were monitored for PNMT and DBH at both mRNA and protein level in PHEO and PGL. Altogether, these results indicate that long term CAT synthesis is not driven by the close environment where the tumor develops and suggest that GC alone is not sufficient to regulate CAT synthesis pathway in PHEO/PGL.

وصف الملف: electronic resource

Relation: http://europepmc.org/articles/PMC4422698?pdf=render; https://doaj.org/toc/1932-6203

URL الوصول: https://doaj.org/article/4e07ed5db2da46fea79b374f86f6a394

المؤلفون: Henryk Zulewski, Ron Ninnis, André R. Miserez, Manfred W. Baumstark, Ulrich Keller

المصدر: Journal of Lipid Research, Vol 39, Iss 2, Pp 380-387 (1998)

مصطلحات موضوعية: apolipoprotein B-100, VLDL, IDL, LDL, FH, FDB, Biochemistry, QD415-436

الوصف: Mutations in the apolipoprotein (apo) B, E (LDL) receptor gene and in the apolipoprotein B-100 gene are the cause of familial hypercholesterolemia (FH) and of familial defective apo B-100 (FDB), respectively. Whether these abnormalities lead to altered production or uptake of very low density lipoprotein (VLDL) or intermediate density lipoprotein (IDL) has not been established previously. Therefore VLDL and IDL apo B-100 kinetics were measured in seven subjects with FH, in six subjects with FDB, and in five normocholesterolemic controls using primed-constant infusions of [1-13C]leucine. Absolute production rates (APR) of VLDL apoB were higher in FH than in controls (27.1 ± 1.9 vs. 17.9 ± 2.1 mg/kg/day P < 0.03). VLDL APR in FDB were between those of FH and controls (24.3 ± 4.8 mg/kg/day), and demonstrated a relatively large inter-individual variability. The increase in VLDL APR in FH resulted in higher fasting serum triglyceride concentrations than in controls (P < 0.05), whereas in FDB triglycerides were between those observed in FH and in controls. A significant correlation was observed between VLDL apoB APR and serum triglycerides in FH and in FDB; the correlation coefficient for all subjects was r = 0.84 (P < 0.0001), indicating that the major determinant of serum triglyceride concentrations was VLDL apoB APR. IDL apoB APR was lower in FH and in FDB compared to controls (P < 0.03 P < 0.02, respectively): and its fractional catabolic rate (FCR) was slightly lower in FH and in FDB, resulting in similar plasma IDL apoB concentrations in all three groups of subjects. IDL apoB APR in FH were negatively correlated with LDL cholesterol concentrations (r = –0.89; P < 0.001); LDL cholesterol concentrations correlated positively with the part of VLDL that did not appear in IDL (r = 0.82 P < 0.02), bypassing therefore the delipidation cascade. In conclusion the data demonstrate increased VLDL apoB production rates in FH. VLDL and IDL kinetics differ when LDL concentrations are elevated either due to a LDL receptor defect or due to defective apolipoprotein B-100.—Zulewski H., R. Ninnis, A. R. Miserez, M. W. Baumstark, and U. Keller. VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S0022227520338992; https://doaj.org/toc/0022-2275

URL الوصول: https://doaj.org/article/baad0b55088e4ef4ad7d47cb952caffb

المؤلفون: Jochen A. Vielhaber, Jasmin Barman-Aksözen, Elisabeth I. Minder, Xiaoye Schneider-Yin, Henryk Zulewski, Anna-Elisabeth Minder

المصدر: Obesity Surgery. 33:1600-1602

مصطلحات موضوعية: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Surgery

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::346e5e78a2baae81fe0d170c9de08ab0
https://doi.org/10.1007/s11695-023-06555-w

المؤلفون: Cynthia Janine Huppermans, Anna Elisabeth Minder, Lukas Frischknecht, Eric Grouzmann, Jean-Louis Blouin, Thierry Nouspikel, Andreas Werner Jehle, Henryk Zulewski

المصدر: Swiss Medical Forum ‒ Schweizerisches Medizin-Forum.

مصطلحات موضوعية: General Medicine

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::ec6b4816d74f10dd9312110951f4a38d
https://doi.org/10.4414/smf.2023.09379

المؤلفون: Cynthia Janine Huppermans, Anna Elisabeth Minder, Lukas Frischknecht, Eric Grouzmann, Jean-Louis Blouin, Thierry Nouspikel, Andreas Werner Jehle, Henryk Zulewski

المصدر: Forum Médical Suisse ‒ Swiss Medical Forum.

مصطلحات موضوعية: General Medicine

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::c144da9739a88e2976e753fbd102c183
https://doi.org/10.4414/fms.2023.09379

المؤلفون: Anna Elisabeth Minder, Christian Pruente, Ursula Schmidt-Erfurth, Roger Lehmann, Alexandra Kaider, Henryk Zulewski, Tilman Drescher, Katja Hatz, Bianca S. Gerendas

المصدر: Diabetes Research and Clinical Practice. 148:234-239

مصطلحات موضوعية: Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Patient Education as Topic, Interquartile range, Diabetes mellitus, Internal medicine, Prevalence, Internal Medicine, medicine, Humans, Insulin, In patient, 030212 general & internal medicine, Stage (cooking), Glycated Hemoglobin, Type 1 diabetes, Diabetic Retinopathy, Dose-Response Relationship, Drug, business.industry, Blood Glucose Self-Monitoring, General Medicine, Diabetic retinopathy, Middle Aged, medicine.disease, Combined Modality Therapy, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, business, Retinopathy

الوصف: Aim Prevalence of retinopathy (DR) in patients with type 1 diabetes treated with education-based intensified insulin therapy (EBIIT) and its association with parameters of glucose control. Methods 151 patients with mean diabetes duration of 14.3 years [SD ± 5.8]) were analyzed. Eyes were examined using standardized 7 field ETDRS (Early Treatment Diabetic Retinopathy Study) settings and images analyzed by a professional external reading center. The glucose exposure over time was defined as HbA1c years, i.e. the sum of the differences between annual mean HbA1c (in %) minus the ideal HbA1c of 6.0% (42 mmol/mol) for each diabetes year (e.g. HbA1c of 8% (64 mmol/mol) over 6 years gives an excess HbA1c of 2.0% (22 for mmol/mol) for 6 years, resulting in 12 HbA1c years (or 131 for mmol/mol)). Results The median (interquartile range) of individual mean HbA1c was 7.3% (6.8–7.8) [56 mmol/mol (51–62)]. and the median HbA1c years was 16.8 (9.1–29.1) [183 mmol/mol (99–319)]. No evidence for DR was found in 59 patients (39%), stage 1 DR in 43 (28.5%), stage 2 in 41 (27.2%), stage 3 in 7 (4.6%) and proliferative DR stage 4 in 1 patient. The best correlation between severity of DR and diabetes control measures was found for HbA1c years (Pearson r = 0.41, p Conclusions In type 1 diabetes EBIIT is associated with good diabetes control and a low prevalence of DR. The cumulative glucose exposure over time given as HbA1c years is the best predictor for development of DR. ClinicalTrials.gov Identifier: NCT02307110.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1cdc2e7d2c49d77eb43fef1e5111b40e
https://doi.org/10.1016/j.diabres.2019.01.016