testosterone (TBS1 / Natesto / TBS 1)

Testosterone disrupts trophoblast function and immune homeostasis via PTGER4/cAMP/RAP1 and ANXA1-FPR1 signaling in PCOS-complicated preeclampsia.

Jiang Ruoan R, Wang Ting T, Yao Yingsha Y, Wu Juanhong J et al.

Polycystic ovary syndrome (PCOS) and preeclampsia (PE) are closely associated conditions, with elevated testosterone levels in PCOS significantly increasing PE risk. This study aimed to elucidate the shared molecular mechanisms linking PCOS and PE, with a particular focus on testosterone-mediated placental dysfunction and immune dysregulation. Integrative bioinformatics analysis of transcriptome data from PCOS and PE patients identified common differentially expressed genes. Human trophoblast cells (HTR-8/SVneo) were treated with testosterone (10 μM) to model pathogenesis. RNA sequencing, RT-qPCR, histopathology, scRNA-seq, and CellChat analysis were used to explore gene regulation and cellular interactions, with functional assays validating key pathways. We identified 418 common DEGs between PCOS and PE using bioinformatics analysis. In vitro, testosterone upregulated PTGER4 in HTR-8/SVneo cells, with PTGER4 showing stepwise increases in PCOS and PCOS-complicated PE, correlating with disease severity. Functional enrichment highlighted Ras-associated protein 1 (RAP1) and immune pathways. Mechanistically, testosterone treatment suppressed trophoblast function (migration and invasion) via PTGER4/cAMP/RAP1 axis suppression. Furthermore, PTGER4/cAMP/RAP1 signaling dysregulation reduced ANXA1 expression in trophoblasts, impaired ANXA1-FPR1-mediated EVT-macrophage communication, and promoted M1 macrophage polarization and pro-inflammatory responses, thereby contributing to the pathogenesis of PCOS-complicated PE. This study provides significant insights into the molecular mechanisms linking PCOS and PE, emphasizing the role of hyperandrogenism in placental dysfunction and immune dysregulation.

The rheological behavior, particle properties and supramolecular structure of low acyl gellan gum fluid gels: impact of the calcium concentration before fluid gel formation.

D'Oria Gabriele G, Zhu Yanshen Y, Limbach Hans Joerg HJ, Hartmann Christoph C et al.

Fluid gels are jammed microgel suspensions obtained by shearing a gelling hydrocolloid during its sol-gel transition. This study focused on calcium-induced low acyl gellan gum (LAGG) fluid gels and investigated the impact of calcium concentration before fluid gel formation on the resulting rheological behavior, fluid gel particle properties, and supramolecular structure. The elasticity and yield stress of fluid gels and quiescently cooled gels reached a maximum when the calcium concentration was increased from 0.78 to (approx.) 30 mmol/kg. Small angle X-ray scattering (SAXS) of fluid gels revealed a progressive increase in gel network connectivity up to the calcium concentration where the peak in rheological properties was observed followed by a less interconnected network at calcium concentrations above the peak. Furthermore, rheological measurements supplemented with free calcium and zeta-potential measurements, support that the decrease after the peak in rheological response is due to the combination of fluid gel particle softening with a decrease in surface charge. The results of this study enable to establish clearer links between rheological behavior, particle properties and supramolecular structure of calcium-induced LAGG fluid gels. This work enables a more effective design of fluid gel properties for different applications from food to pharma and biomaterials.

Designing soy protein amyloid fibrils-high methoxyl pectin composite gel as a potential dysphagia food: Focus on interaction exploration and delivery properties.

Feng Jianling J, Yang Bowen B, Han Xu X, Tong Xiaohong X et al.

In this study, a composite gel system oriented by dysphagia diet was constructed by soy protein amyloid fibrils (SAF) crosslinking high methoxyl pectin (HMP). The interaction mode, structure and properties of composite gels at different pH values and composite ratios were investigated. Results showed that HMP enhanced the gel properties of SAF through non-covalent interaction and steric hindrance of its own polysaccharide chain. Among them, the network pores of the pH 7.0 group gel were smaller, and the structure was more uniform than those of pH 2.0 group gel. Moreover, the composite gel changed from protein-based to polysaccharide-based as the volume ratio of SAF and HMP decreased, and the size of the intermolecular interaction force and the three-dimensional network structure changed. In particular, pH 7.0-SAF-HMP-1:1 had the optimal water holding capacity (91.37 ± 2.14%), rheology, textural properties, and lubricating performance. pH 7.0-SAF-HMP-1:1 was classified as Level 5 according to the International Dysphagia Diet Standardization Initiative and can be considered as potential transition foods. Furthermore, when the curcumin was 3 mg/mL, it had the highest embedding rate (83.62 ± 1.27%), bioaccessibility (74.87 ± 0.82%), and stability. These studies provided a theoretical basis for the ideal gels for dysphagia and functional foods.

Ultrasound gel: an overlooked sustainability challenge.

Ip Vivian H Y VHY, Bloc Sébastien S, Sondekoppam Rakesh V RV