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BioTeSys ist active as speaker at public events and publishes scientific articles. You can find an overview of these publications here.

Publication: 16. September 2023

Associations of circulating GDF15 with combined cognitive frailty and depression in older adults of the MARK-AGE study

Growth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with combined cognitive-frailty-and-depression in older (i.e. ≥ 55 years) and younger adults of the MARK-AGE study. In the present work, samples and data of MARK-AGE ("European study to establish bioMARKers of human AGEing") participants (N = 2736) were analyzed. Cognitive frailty was determined by the global cognitive functioning score (GCF) and depression by the Self-Rating Depression Scale (SDS score). Cross-sectional associations were determined by unadjusted and by age, BMI, sex, comorbidities and hsCRP-adjusted linear and logistic regression analyses. Cognitive frailty, depression, age and GDF15 were significantly related within the whole study sample. We conclude that plasma GDF15 concentrations are significantly associated with combined cognitive-frailty-and-depression status and, with cognitive frailty and depressive symptoms separately in old as well as young community-dwelling adults.

Publication: 15. July 2023

Comparison of the Hologic Genius Digital Diagnostics System with the ThinPrep Imaging System-A retrospective assessment

Digital cytology (DC) with artificial intelligence (AI) is a new approach. The authors compared DC with liquid-based cytology (LBC) using computer assistance (CAS) in a retrospective, noninterventional study. In total, 1994 ThinPrep LBC slides (Hologic), which were previously analyzed in 2020 using an imaging system with CAS in routine cotesting for cytology/human papillomavirus, were reviewed in a blinded mode using the Genius Digital Diagnostics System (Hologic). In 86.56% of cases, a complete match between both systems was observed using the same cytology categories. When also considering the histology results, the match was 90.37%. In addition, when a cytology follow-up and/or a retrospective review was applied, the match reached 97.34%. In only 0.65% of cases was a major discrepancy observed (two grades of cytology or a low-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion [LSIL/HSIL] shift), and none were identified by DC. Significantly more cases of higher severity (atypical squamous cells cannot exclude high grade [ASC-H], high-grade squamous intraepithelial lesion [HSIL]) were identified with DC, and its negative predictive value was higher. The screening time was significantly shorter with DC. With the Genius system for DC, the sensitivity for HSIL+/ASC-H and the specificity for LSIL and HSIL were superior to LBC and CAS. Screening time was significantly lower.

Publication: 04. May 2023

Uncovering the Relationship between Selenium Status, Age, Health, and Dietary Habits: Insights from a Large Population Study including Nonagenarian Offspring from the MARK-AGE Project

An inadequate selenium (Se) status can accelerate the aging process, increasing the vulnerability to age-related diseases. The study aimed to investigate plasma Se and Se species in a large population, including 2200 older adults from the general population (RASIG), 514 nonagenarian offspring (GO), and 293 GO Spouses (SGO). Plasma Se levels in women exhibit an inverted U-shaped pattern, increasing with age until the post-menopausal period and then declining. Conversely, men exhibit a linear decline in plasma Se levels with age. Subjects from Finland had the highest plasma Se values, while those from Poland had the lowest ones. Plasma Se was influenced by fish and vitamin consumption, but there were no significant differences between RASIG, GO, and SGO. Plasma Se was positively associated with albumin, HDL, total cholesterol, fibrinogen, and triglycerides and negatively associated with homocysteine. Fractionation analysis showed that Se distribution among plasma selenoproteins is affected by age, glucometabolic and inflammatory factors, and being GO or SGO. These findings show that sex-specific, nutritional, and inflammatory factors play a crucial role in the regulation of Se plasma levels throughout the aging process and that the shared environment of GO and SGO plays a role in their distinctive Se fractionation.

Publication: 30. March 2023

Skin penetration of active folate salts and their effects on wound healing in vitro: new approaches for dermal folate application

The skin has a high demand for folates because of its constant renewal and growth. Folates play an important role in the metabolism of healthy skin and in the regeneration of irritated or injured skin. The high proliferation rate supports wound healing in chronic and degenerative skin diseases. In contrast to systemic folate administration, there is little known on skin penetration of folates after topical application. Therefore, skin penetration with L-formyltetrahydrofolate di-arginine salt (L-FTHF-di-arginine), L-formyltetrahydrofolate calcium gluconate mixture (L-FTHF-Ca) and L-methyltetrahydrofolate dicholine salt (L-MTHF-dicholine) was studied. We investigated the epidermal penetration of 2.5% aqueous solution of L-FTHF di-arginine, L-FTHF Ca and L-MTHF dicholine using in vitro reconstructed epidermal skin models. In order to assess an effect on wound healing in vitro, the selected folates were tested in a keratinocyte scratch assay. Analysis of the examined folates in the cell culture medium located opposite of the application site showed their penetration through the reconstructed epidermal model. In epidermal models to which L-FTHF di-arginine was added, L-MTHF dicholine was detected on the opposite site. L-FTHF salts were partially converted to L-MTHF. Improved wound healing was shown in keratinocyte scratch assay when the selected folates were added to the medium.

Publication: 26. January 2023

Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study

Aging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be further aggravated by antioxidant nutrient deficiency. Low plasma carotenoids are associated with an increased risk of inflammation and cellular damage and predict mortality. However, no evidence is yet available on the relationship between antioxidants and the blood bacterial DNA (BB-DNA). Therefore, this study aimed to compare BB-DNA from (a) GO (nonagenarian offspring), (b) age-matched controls (Randomly recruited Age-Stratified Individuals from the General population [RASIG]), and (c) spouses of GO (SGO) recruited in the MARK-AGE project, as well as to investigate the association between BB-DNA, behavior habits, Charlson Comorbidity Index (CCI), leucocyte subsets, and the circulating levels of some antioxidants and oxidative stress markers. We provide evidence of a reduced BB-DNA in individuals from long-living families and their spouses, suggesting a decreased microbial dysbiosis and bacterial systemic translocation. BB-DNA was also associated with smoking, CCI, leukocyte subsets, and some redox biomarkers in older participants.

Publication: 15. January 2023

An exploratory study on the effect of choline and folate deficiency on levels of vascularization proteins and transcription factors in first trimester trophoblast HTR-8/SVneo cells

We studied the effect of choline and folate deficiencies on levels of predetermined placental proteins during early development. HTR-8/SVneo cells were incubated under choline and folate deficiency conditions and levels of some placental proteins were measured using ELISA methods. As a conlcusion, LRP2 and CDX2 are likely to be molecular targets for early choline and folate deficiencies in human trophoblast cells. The results should be confirmed in animal models and in other models of placental cells.

Publication: 10. January 2023

Association of Torquetenovirus Viremia with Physical Frailty and Cognitive Impairment in Three Independent European Cohorts

Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. The findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV's clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.

Publication: 22. December 2022

Association between Maternal Choline, Fetal Brain Development, and Child Neurocognition: Systematic Review and Meta-Analysis of Human Studies

We studied associations between prenatal and early postnatal choline intake, brain development, and neurocognitive function of children. We conducted a systematic review followed by a meta-analysis and critical appraisal of human studies published from 1997 to 2021. Thirty publications were identified. The meta-analysis included 5 of 7 case-control studies studying neural tube defects (NTDs) in relation to maternal choline intakes/circulating concentrations. Despite limitations of available trials and observational studies, higher maternal choline intake was likely to be associated with better child neurocognition/neurodevelopment. The results should be used to guide choline intake recommendations in pregnancy and lactation, especially because most young women are not achieving the reference intake of choline.

Publication: 21. July 2022

Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.

Publication: 28. May 2022

Synbiotic Compositions of Bacillus megaterium and Polyunsaturated Fatty Acid Salt Enable Self-Sufficient Production of Specialized Pro-Resolving Mediators

Specialized pro-resolving mediators (SPM) have emerged as crucial lipid mediators that confer the inflammation-resolving effects of omega-3 polyunsaturated fatty acids (n-3 PUFA). To overcome the limitations of conventional n-3 PUFA supplementation strategies, we devised a composition enabling the self-sufficient production of SPM in vivo. A pilot study was performed to test if a synbiotic Bacillus megaterium/n-3 PUFA formulation increases SPM levels in vivo. Supplementation with a synbiotic capsule product led to significantly increased plasma levels of hydroxy-eicosapentaenoic acids (5-HEPE, 15-HEPE, 18-HEPE) and hydroxy-docosahexaenoic acids (4-HDHA, 7-HDHA) as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in healthy humans.