@article{nadegger_characterization_2025,

title = {Characterization of Phyllobilins in Hops: Antioxidant and Potentially Bitter Senescence-Related Metabolites},

author = {Christian Nadegger and Patricia Frei and Christian A. Elvert and Cornelia A. Karg and Johanna M. Gostner and Jonathan S. Lindsey and Christoph R. Kreutz and Stefan Schwaiger and Thomas Müller and Simone Moser},

doi = {10.1021/acs.jafc.5c03549},

issn = {1520-5118},

year  = {2025},

date = {2025-07-01},

journal = {Journal of Agricultural and Food Chemistry},

abstract = {Hops is of high relevance to the food sector, and increasingly valued as medicinal plant. Its complex phytochemistry includes phenolic compounds and bitter prenylated polyketides, but phyllobilins─bioactive linear tetrapyrroles from chlorophyll catabolism─remain underexplored. In this work, several dioxobilin-type phylloleucobilins (DPleBs) and phylloxanthobilins (DPxBs) were identified in yellowish leaves of common hops (Humulus lupulus). Isolation from 107 g of leaves yielded 0.24 mg of Hl-DPleB-28 and 0.80 mg of Hl-DPxB-31. Structural elucidation via UV/vis, HR-MS2, and NMR confirmed those as new phyllobilins, featuring an unusual hydroxylation motif, indicating an uncharacterized metabolic pathway. Hl-DPxB constituted about 40% of HPLC peak areas at 420 nm in yellow leaves, suggesting its significant role in the visual senescence of hops. Hl-DPxB-31 possessed high antioxidative activity, comparable to quercetin. A virtual tool predicted over 60% bitterness probability. These findings expand the phytochemical profile of hops and highlight potential for upcycling leaf waste.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{robertson_increased_2025,

title = {Increased immune activation in people living with HIV on antiretroviral therapy but not when compared with persons on HIV preexposure prophylaxis},

author = {Josefina Robertson and Arvid Edén and Aylin Yilmaz and Lars-Magnus Andersson and Lars Hagberg and Kristina Nyström and Staffan Nilsson and Carl-Johan Treutiger and Petra Tunbäck and Johanna M. Gostner and Henrik Zetterberg and Magnus Gisslén},

doi = {10.1080/23744235.2025.2515157},

issn = {2374-4243},

year  = {2025},

date = {2025-06-01},

journal = {Infectious Diseases (London, England)},

pages = {1–8},

abstract = {BACKGROUND: Residual immune activation is common in people living with HIV (PWH) despite antiretroviral therapy (ART) and may be associated with HIV-specific, as well as lifestyle-related factors. 

OBJECTIVE: We aimed to investigate markers of immune activation and neuronal injury in PWH on ART compared with controls with similar lifestyle. 

METHODS: Cerebrospinal fluid (CSF) and blood were collected from 50 men who have sex with men (MSM) with HIV on ART, 50 HIV-negative MSM on preexposure prophylaxis (PrEP), and 25 HIV-negative controls without PrEP. β2-microglobulin, neopterin, and neurofilament light protein (NfL) were analyzed. Cytomegalovirus and herpes simplex virus-2 serostatus, as well as sexually transmitted bacterial infections were registered. 

RESULTS: Serum and CSF β2-microglobulin and neopterin did not differ significantly between MSM with HIV and MSM on PrEP. However, both groups had significantly higher serum levels of β2-microglobulin and neopterin compared with HIV-negative controls without PrEP. Age-adjusted CSF NfL levels were also similar in MSM with HIV and MSM on PrEP, but higher than in controls without PrEP. A recent syphilis infection was associated with increased immune activation in CSF and blood. 

CONCLUSION: Increased levels of immune activation and neuronal injury markers were found in virologically suppressed MSM with HIV and MSM on PrEP compared with controls. These findings imply that other factors than HIV contribute to the residual immune activation and impact on neurons observed in MSM with HIV on ART, and emphasize the importance of appropriate controls with similar lifestyle in studies of biomarkers in PWH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hofer_myrobalan_2025,

title = {Myrobalan Fruit Extracts Modulate Immunobiochemical Pathways In Vitro.},

author = {Stefanie Hofer and Marcel Jenny and Angela Klein and Kathrin Becker and Lucia Parráková and Florian Überall and Markus Ganzera and Dietmar Fuchs and Hubert Hackl and Pablo Monfort-Lanzas and Johanna M. Gostner},

doi = {10.3390/antiox14030350},

issn = {2076-3921},

year  = {2025},

date = {2025-03-01},

journal = {Antioxidants (Basel, Switzerland)},

volume = {14},

number = {3},

abstract = {Myrobalan fruits are important ingredients of traditional remedies, such as the Ayurvedic formulation Triphala or the Tibetan formulation Bras bu 3. Myrobalan-containing remedies are described to have positive effects on metabolism, the cardiovascular system, and the immune system. The chemical composition of botanical mixtures can be very complex, and it is often impossible to identify individual compounds as specific active ingredients, which suggests a multi-target mode of action. In this in vitro study, the effect of myrobalan extracts in human cell models was investigated to gain more information about the molecular mechanism of action and to find possible synergistic effects. Direct and indirect antioxidant effects were investigated, and the activation of immunobiochemical metabolic pathways involved in the cellular immune response was examined in cell lines treated with extracts of the fruits of Phyllanthus emblica, Terminalia chebula and Terminalia bellirica, as well as a combination of them. In particular, a synergistic effect on the activation of the endogenous antioxidant defence system was observed with the combined treatment of the three fruit extracts. An integrated transcriptome analysis of cells treated with a combination of fruit extracts confirmed an effect on immune pathways, oxidative stress, and detoxification processes. This study shows the modulation of various signalling pathways and cellular processes that may be part of the multi-target mechanism of individual and combined myrobalan fruit extracts. Although the results are limited to in vitro data, they contribute to a better understanding of how botanical mixtures work and provide hypotheses for further research.},

note = {Place: Switzerland},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ulfhammer_asymptomatic_2025,

title = {Asymptomatic Cerebrospinal Fluid HIV-1 Escape: Incidence and Consequences.},

author = {Gustaf Ulfhammer and Aylin Yilmaz and Åsa Mellgren and Erika Tyrberg and Erik Sörstedt and Lars Hagberg and Johanna Gostner and Dietmar Fuchs and Henrik Zetterberg and Staffan Nilsson and Kristina Nyström and Arvid Edén and Magnus Gisslén},

doi = {10.1093/infdis/jiae555},

issn = {1537-6613 0022-1899},

year  = {2025},

date = {2025-02-01},

journal = {The Journal of infectious diseases},

volume = {231},

number = {2},

pages = {e429–e437},

abstract = {BACKGROUND: The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSFE) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSFE in a Swedish HIV cohort. METHODS: Neuroasymptomatic people with HIV (PWH) who have been on ART for at least 6 months with suppressed plasma viral load were followed longitudinally. CSFE was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or CSF HIV-1 RNA exceeding that in plasma when both were quantifiable. Paired CSF and plasma were analyzed for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio. RESULTS: Asymptomatic CSFE (cutoff 50 copies/mL) was found in 4 of 173 PWH (2%) and 5 of 449 samples (1%). The corresponding proportions were 8% of PWH and 4% for samples using a 20 copies/mL cutoff for CSF HIV-1 RNA. CSFE samples (cutoff 20 copies/mL) had a 25% higher geometric mean of CSF neopterin (P = .01) and 8% higher albumin ratio (P = .04) compared to samples without CSFE. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (≥ 3 cells/μL) in samples with CSFE was 3.9 (P = .004), compared to samples without elevated CSF viral load. CONCLUSIONS: Asymptomatic CSFE was identified in only 4 (2%) PWH, with no cases of continuous CSFE observed. Increased CSF HIV-1 RNA was associated with biomarkers of CNS immune activation and blood-brain barrier impairment, but not with biomarkers of neuronal injury.},

note = {Place: United States},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{burtscher_interplay_2025,

title = {The interplay of NAD and hypoxic stress and its relevance for ageing.},

author = {Johannes Burtscher and Vanna Denti and Johanna M. Gostner and Alexander Kh Weiss and Barbara Strasser and Katharina Hüfner and Martin Burtscher and Giuseppe Paglia and Martin Kopp and Tobias Dünnwald},

doi = {10.1016/j.arr.2024.102646},

issn = {1872-9649 1568-1637},

year  = {2025},

date = {2025-02-01},

journal = {Ageing research reviews},

volume = {104},

pages = {102646},

abstract = {Nicotinamide adenine dinucleotide (NAD) is an essential regulator of cellular metabolism and redox processes. NAD levels and the dynamics of NAD metabolism change with increasing age but can be modulated via the diet or medication. Because NAD metabolism is complex and its regulation still insufficiently understood, achieving specific outcomes without perturbing delicate balances through targeted pharmacological interventions remains challenging. NAD metabolism is also highly sensitive to environmental conditions and can be influenced behaviorally, e.g., by exercise. Changes in oxygen availability directly and indirectly affect NAD levels and may result from exposure to ambient hypoxia, increased oxygen demand during exercise, ageing or disease. Cellular responses to hypoxic stress involve rapid alterations in NAD metabolism and depend on many factors, including age, glucose status, the dose of the hypoxic stress and occurrence of reoxygenation phases, and exhibit complex time-courses. Here we summarize the known determinants of NAD-regulation by hypoxia and evaluate the role of NAD in hypoxic stress. We define the specific NAD responses to hypoxia and identify a great potential of the modulation of NAD metabolism regarding hypoxic injuries. In conclusion, NAD metabolism and cellular hypoxia responses are strongly intertwined and together mediate protective processes against hypoxic insults. Their interactions likely contribute to age-related changes and vulnerabilities. Targeting NAD homeostasis presents a promising avenue to prevent/treat hypoxic insults and - conversely - controlled hypoxia is a potential tool to regulate NAD homeostasis.},

note = {Place: England},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{seizer_case_2025,

title = {Case Report: Endocrine, immune and disease dynamics in a patient with rheumatoid arthritis during flare and medication change},

author = {Lennart Seizer and Johanna M. Gostner and Christoph Garbers and Melina Licht and Sebastian Sager and Andreas Brandl and Christian Schubert},

doi = {10.3389/fimmu.2025.1491475},

issn = {1664-3224},

year  = {2025},

date = {2025-01-01},

journal = {Frontiers in Immunology},

volume = {16},

pages = {1491475},

abstract = {OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease of mostly unknown etiology and pathophysiology. In this integrative single-case study on a patient with RA, we had the unique opportunity to closely monitor the individual dynamics of endocrine, immune and disease variables during a naturally occurring flare-up and subsequent medication change. 

METHODS: The 59-year-old female RA patient collected her entire urine over 30 days in 12-h intervals (60 consecutive measurements in total). Subsequently, cortisol, interleukin-6 (IL-6), orosomucoid-2 (ORM-2), neopterin and creatinine levels were determined in the urine samples. Further, each morning and evening, the patient completed the DIARI, a set of questionnaires on variables such as perceived pain, perceived RA disease activity and emotional states. Once a week, the patient was interviewed online and had an appointment with her rheumatologist, in which several indices of RA disease activity were determined: SDAI, CDAI and DAS28. From these data various time series were constructed for statistical analysis. 

RESULTS: RA disease state increased from low to high activity during the first 12 study days. Thereupon, the medication was changed, which proved effective in reducing RA disease activity. However, the levels of urinary neopterin, urinary IL-6 and urinary ORM-2 did not show any response, neither to the increasing disease activity nor the medication change. The patient's daily reports on pain, RA disease activity, emotional states and body temperature, however, mirrored the course of the rheumatologic indices. 

CONCLUSION: This integrative single-case study clearly demonstrated the importance of process analysis for the evaluation of therapeutic measures in RA. In the studied patient, urinary levels of neopterin, IL-6 and ORM-2 were not found to be appropriate biomarkers of short-term fluctuations in RA disease activity. Instead, the results reported by the patient proved to be a useful tool for ambulatory and longitudinal monitoring of RA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{monfort-lanzas_modeling_2025,

title = {Modeling omics dose-response at the pathway level with DoseRider.},

author = {Pablo Monfort-Lanzas and Johanna M. Gostner and Hubert Hackl},

doi = {10.1016/j.csbj.2025.04.004},

issn = {2001-0370},

year  = {2025},

date = {2025-01-01},

journal = {Computational and structural biotechnology journal},

volume = {27},

pages = {1440–1448},

abstract = {The generation of omics data sets has become an important approach in modern pharmacological and toxicological research as it can provide mechanistic and quantitative information on a large scale. Analyses of these data frequently revealed a non-linear dose-response relationship underscoring the importance of the modeling process to infer biological exposure limits. A number of tools have been developed for dose-response modeling and various thresholds have been defined as a quantitative representation of the effect of a substance, such as effective concentrations or benchmark doses (BMD). Here we present DoseRider an easy-to-use web application and a companion R package for linear and non-linear dose-response modeling and assessment of BMD at the level of biological pathways or signatures using generalized mixed effect models. This approach allows to analyze custom or provided multi-omics data such as RNA sequencing or metabolomics data and its annotation of a collection of pathways and gene sets from various species. Moreover, we introduce the concept of the trend change doses (TCDs) as a numerical descriptor of effects derived from complex dose-response curves. The usability of DoseRider was demonstrated by analyses of RNA sequencing data of bisphenol AF (BPAF) treatment of a human breast cancer cell line (MCF-7) at 8 different concentrations using gene sets for chemical and genetic perturbations (MSigDB). The BMD for BPAF and a set of genes upregulated by estrogen in breast cancer was 0.2 µM (95 %-CI 0.1-0.5 µM) and the lowest TCD (TCD1) was 0.003 µM (95 %-CI 0.0006-0.01 µM). The comprehensive presentation of the results underlines the suitability of the system for pharmacogenomics, toxicogenomics, and applications beyond.},

note = {Place: Netherlands},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kyvelidou_dendritic_2024,

title = {Dendritic cells under the control of the preimplantation embryo secretome: an in vitro study.},

author = {Christiana Kyvelidou and Sofia Haselrieder and Maria Gierke and Johanna M. Gostner and Wolfgang Biasio and Barbara Wirleitner and Christine Heufler and Bettina Toth and Susanne Hofer-Tollinger},

doi = {10.1186/s12958-024-01319-2},

issn = {1477-7827},

year  = {2024},

date = {2024-11-01},

journal = {Reproductive biology and endocrinology : RB&E},

volume = {22},

number = {1},

pages = {150},

abstract = {OBJECTIVE: To study the crosstalk between maternal immune cells and the developing embryo by investigating the immunogenic properties of human blastocyst spent media (SM) on dendritic cells. METHODS: In this prospective multicenter experimental study, human preimplantation embryo spent media were collected after blastocyst formation, grouped based on successful or unsuccessful implantation, and analyzed by protein array or used to stimulate monocyte derived dendritic cells (moDC). The immunomodulatory properties of SM on moDC were investigated by analyzing changes in phenotype, cytokine secretion, indoleamine 2,3-dioxygenase (IDO) activity, and ability to activate T cells. RESULTS: A plethora of cytokines and growth factors secreted from preimplantation embryos was detected. Exposure to embryo SM altered the phenotype of moDC in a manner dependent on the implantation outcome. Specifically, SM from non-implanted embryos increased the expression of co-stimulatory molecules and activation markers on moDC. Furthermore, SM treated dendritic cells secreted low levels of cytokines and growth factors and were able to stimulate naïve T cells. Activation of IDO was decreased in moDC after stimulation with SM. CONCLUSIONS: Our findings show that human preimplantation embryos secrete an abundance of molecules with the ability to significantly affect and even regulate immune cells in their environment.},

note = {Place: England},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hu_changes_2024-1,

title = {Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection.},

author = {Zicheng Hu and Paola Cinque and Ameet Dravid and Lars Hagberg and Aylin Yilmaz and Henrik Zetterberg and Dietmar Fuchs and Johanna Gostner and Kaj Blennow and Serena S. Spudich and Laura Kincer and Shuntai Zhou and Sarah Beth Joseph and Ronald Swanstrom and Richard W. Price and Magnus Gisslén},

doi = {10.1371/journal.ppat.1012470},

issn = {1553-7374 1553-7366},

year  = {2024},

date = {2024-09-01},

journal = {PLoS pathogens},

volume = {20},

number = {9},

pages = {e1012470},

abstract = {Using the Olink Explore 1536 platform, we measured 1,463 unique proteins in 303 cerebrospinal fluid (CSF) specimens from four clinical centers contributed by uninfected controls and 12 groups of people living with HIV-1 infection representing the spectrum of progressive untreated and treated chronic infection. We present three initial analyses of these measurements: an overview of the CSF protein features of the sample; correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament light chain protein (NfL) concentrations; and comparison of CSF proteins in HIV-associated dementia (HAD) and neurosymptomatic CSF escape (NSE). These reveal a complex but coherent picture of CSF protein changes with highest concentrations of many proteins during CNS injury in the HAD and NSE groups and variable protein changes across the course of systemic HIV-1 progression that included two common patterns, designated as lymphoid and myeloid patterns, related to principal involvement of their underlying inflammatory cell lineages. Antiretroviral therapy reduced CSF protein perturbations, though not always to control levels. The dataset of these CSF protein measurements, along with background clinical information, is posted online. Extended studies of this unique dataset will supplement this report to provide more detailed characterization of the dynamic impact of HIV-1 infection on the CSF proteome across the spectrum of HIV-1 infection, advancing the mechanistic understanding of HIV-1-related CNS pathobiology.},

note = {Place: United States},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{monfort-lanzas_exonsurfer_2024,

title = {ExonSurfer: a web-tool to design primers at exon-exon junctions.},

author = {Pablo Monfort-Lanzas and Elena Cristina Rusu and Lucia Parrakova and Cornelia A. Karg and Dorina-Elina Kernbichler and Dietmar Rieder and Peter Lackner and Hubert Hackl and Johanna M. Gostner},

doi = {10.1186/s12864-024-10456-2},

issn = {1471-2164},

year  = {2024},

date = {2024-06-01},

journal = {BMC genomics},

volume = {25},

number = {1},

pages = {594},

abstract = {BACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) with intercalating dyes is one of the main techniques to assess gene expression levels used in basic and applied research as well as in diagnostics. However, primer design for RT-qPCR can be complex due to the high demands on primer quality. Primers are best placed on exon junctions, should avoid polymorphic regions, be specific to the target transcripts and also prevent genomic amplification accurately, among others. Current software tools manage to meet all the necessary criteria only insufficiently. Here, we present ExonSurfer, a novel, user-friendly web-tool for qPCR primer design. RESULTS: ExonSurfer combines the different steps of the primer design process, encompassing target selection, specificity and self-complementarity assessment, and the avoidance of issues arising from polymorphisms. Amplification of potentially contaminating genomic DNA is avoided by designing primers on exon-exon junctions, moreover, a genomic alignment is performed to filter the primers accordingly and inform the user of any predicted interaction. In order to test the whole performance of the application, we designed primer pairs for 26 targets and checked both primer efficiency, amplicon melting temperature and length and confirmed the targeted amplicon by Sanger sequencing. Most of the tested primers accurately and selectively amplified the corresponding targets. CONCLUSION: ExonSurfer offers a comprehensive end-to-end primer design, guaranteeing transcript-specific amplification. The user interface is intuitive, providing essential specificity and amplicon details. The tool can also be used by command line and the source code is available. Overall, we expect ExonSurfer to facilitate RT-qPCR set-up for researchers in many fields.},

note = {Place: England},

keywords = {},

pubstate = {published},

tppubtype = {article}

}