Journals
2025 EN
Torozan Dominique A. · Laczny Cédric Christian · Roomp Kirsten
+3 more
ABSTRACT Background We explored the interaction between the oral microbiome and the development of radiation‐induced mucositis in patients with head and neck squamous cell cancer (HNSCC) undergoing chemoradiotherapy (CRT). We prospectively studied the oral microbiome and compared it to healthy controls. Additionally, we compared patients with low‐grade (LGM) vs. high‐grade mucositis (HGM). Methods Ten HNSCC patients scheduled for CRT were included. Saliva samples were characterized prior to, during, and nine months after CRT using metagenomic sequencing. We similarly characterized samples from seven healthy controls. We assessed alpha and beta diversity and examined abundances at different taxonomic levels between (sub)groups. Results Patients exhibited significantly reduced alpha diversity compared to controls at all times (p ⟨ 0.05). Differential abundance of taxa between patients and controls was observed at baseline. In patients, the relative abundance of Staphylococcus aureus and Escherichia coli increased significantly during CRT. Capnocytophaga spp. was associated with the definitive CRT patients' subgroup. At baseline, two fungal families (Melampsoraceae and Herpotrichiellaceaea) were more abundant in patients who later developed HGM. No differentially abundant taxa were found between LGM vs. HGM during irradiation. Conclusion Our findings support the hypothesis that CRT, as well as HNSCC itself, influences the composition of the oral microbiome. Microbial markers found in patients who later developed HGM should be evaluated using independent cohorts to qualify their specific biomarker potential.
Journals
2025 EN
Grohmann Dominique · Banham Claire · Mengoni Silvana
+2 more
Abstract Objectives The aim of this study was to conduct a pilot evaluation of a novel six‐week school‐based intervention (‘Haven Schools’) on young people's psychological wellbeing. Methods One hundred and forty‐one students (ages 12–16 years) from 11 schools in England attended up to six sessions of the intervention at their school during the day. Psychological wellbeing was evaluated at each session using the overall score on the Young Person's Core‐10 (YP CORE‐10) outcome measure, and anxiety and self‐harm were evaluated using individual questions in the YP CORE‐10. Results Participants' psychological wellbeing was significantly better at their last session compared to their first session. Anxiety and thoughts of self‐harm were also significantly lower in last sessions compared to first sessions. Attendance was good, with 64% attending at least four sessions ( M = 3.99 sessions attended). Conclusions The Haven Schools programme appears to have promising initial results; however, further investigation using a control group and longer‐term follow up are warranted. Patient Consent Statement This was an analysis of secondary data used to evaluate the programme, and therefore did not fall within the remit required for ethical review. Each school managed the issue of parental consent differently depending on their own rules. One school felt that it was not necessary to get parental consent as they felt it could be a barrier to some young people attending as they may not want their parents to know. However, most schools sent parents of students who indicated an interest an information letter, and asked parents to email the school with consent.
Journals
2025 EN
Elmi Abdirahman · Zengin Gokhan · Said Mohamed A.
+8 more
ABSTRACT Boscia coriacea Graells (BC), Grewia erythraea (Schweinf.) Chiov. (GE), Ochradenus baccatus Delile (OB), and Orthosiphon pallidus Royle ex Benth. (OP) are medicinal plants used in Djibouti. They were evaluated to determine their total phenolic content (TPC), flavonoid content (TFC), and phytochemical profile using HPLC–MS/MS. Additionally, their antioxidant capacity was assessed through five various methods. Enzymatic activities were also measured, focusing on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α‐amylase, α‐glucosidase, and tyrosinase. OP extract had the highest TPC and exhibited the best antioxidant capacity, whereas OB and BC extracts had the highest TFC. Twenty‐seven compounds were identified and quantified by LCMS. GE extract demonstrated the highest AChE activity, whereas OP extract had the highest BChE activity. BC was most active against α‐amylase and α‐glucosidase, and only GE and OP extracts showed tyrosinase inhibition in vitro. In silico analysis, the compounds were optimized and docked to the human tyrosinase‐related protein 1 using AutoDock Vina, with absorption, distribution, metabolism, and elimination to evaluate their suitability based on key therapeutic criteria. Chlorogenic, neochlorogenic, gallic acids, and quercetin emerged as promising tyrosinase inhibitors. These plants can be a viable source in the prevention and treatment related to tyrosinase enzyme inhibition.
Journals
2025 EN
Li Qifei · Claes Sandra · Van Loy Tom
+3 more
ABSTRACT The human chemokine receptor 8 (CCR8) received attention as target for the treatment of various autoimmune disorders. Phenoxybenzylpiperidine analogues are known to act as CCR8 agonists, although their structure–activity relationship (SAR) has been studied to a limited extent. In this study, the SAR of phenoxybenzylpiperidinyl analogues was explored in a systematic way by fusion or insertion of various heterocyclic groups on the piperidinyl ring, yielding a set of 21 novel phenoxybenzylpiperidinyl derivatives. Evaluation of potential CCR8 agonism in a cell‐based assay revealed that the newly synthesized compounds were clearly less potent than the reference compounds, with the most potent analogues displaying an EC 50 value of 4 µM. Despite the fact that CCR8 agonism tolerated quite some structural variety on the piperidinyl moiety, this study demonstrated that the substitution pattern has some structural constraints for CCR8 agonism.
Journals
2025 EN
Marshall Andrea G. · Stephens Dominique · Neikirk Kit
+35 more
ABSTRACT Alzheimer's Disease (AD) is a global health issue, affecting over 6 million people in the United States, with that number expected to increase as the population ages. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. In this study, we measured hemodynamic parameters related to cardiovascular and cerebrovascular function in 5xFAD mice with AD and their littermates. Specifically, we measured cardiovascular pulse wave velocity parameters, a marker of arterial stiffness and cardiovascular risk, and cerebrovascular pulse wave velocity, a novel technique to measure cerebral arterial stiffness. Our results showed that while 5xFAD mice exhibited significant differences in ejection time, pulse pressure, and Tei index, many other cardiovascular and cerebral parameters were not different. Despite reports that amyloid plaque deposition begins at an early age of 1.5 months in 5xFAD mice, our results did not indicate significant cardiovascular changes. Studies to elucidate cardiovascular and cerebrovascular parametric changes should be done at later ages where the underlying changes are more profound.
Journals
2025 UN
Marshall Andrea G. · Stephens Dominique · Neikirk Kit
+35 more
The cover image is based on the article Alterations in Cardiovascular Parameters in 5xFAD Murine Model by Antentor Hinton et al., https://doi.org/10.1002/cbf.70138
Journals
2025 EN
Trujillo Marissa N. · Jennings Erin Q. · Farrera Dominique O.
+8 more
Abstract Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme in de novo Ser biosynthesis. Numerous metabolic pathways rely on Ser as a precursor, most notably one‐carbon metabolism, glutathione biosynthesis, and de novo nucleotide biosynthesis. To facilitate proliferation, many cancer cells shunt glycolytic flux through this pathway, placing PHGDH as a metabolic liability and feasible therapeutic target for the treatment of cancer. Herein, we demonstrate the post‐translational modification (PTM) of PHGDH by lactoylLys. These PTMs are generated through a non‐enzymatic acyl transfer from the glyoxalase cycle intermediate, lactoylglutathione (LGSH). Knockout of the primary LGSH regulatory enzyme, glyoxalase 2 (GLO2), results in increased LGSH and resulting lactoylLys modification of PHGDH. These PTMs reduce enzymatic activity, resulting in a marked reduction in intracellular Ser. Using stable isotope tracing, we demonstrate reduced flux through the de novo Ser biosynthetic pathway. Collectively, these data identify PHGDH as a target for modification by lactoylLys, resulting in reduced enzymatic activity and reduced intracellular Ser.
Journals
2025 EN
Möller Christina · Terholsen Henrik · Schmöker Ole
+13 more
Abstract The supply of blood products such as red blood cells poses a challenge due to rising demand and declining donor numbers. Careful matching of blood products of different types is required. Only type O of the blood types A, B, AB and O can be received by any patient without transfusion incompatibilities. Therefore, O‐type blood can be considered “universal blood” and is especially needed in emergency situations. In this study, we focused on the conversion of the B antigen by enzymatic deglycosylation to generate the H antigen determining O‐type blood. For this, we characterized several previously unstudied α‐1,3‐galactosidases belonging to the GH110 family. Our findings revealed that the α‐1,3‐galactosidase from Pedobacter panaciterrae (PpaGal) exhibits superior efficiency compared to previously described galactosidases. We further increased the activity of PpaGal by 2.5‐fold using site‐directed mutagenesis. Moreover, we solved two crystal structures of PpaGal, one in the apo‐state and another in complex with d ‐galactose. The combination of our mutagenesis study with the solved crystal structures provides valuable information to guide further optimization of PpaGal or other B antigen converting enzymes paving the way for the easier production of universal blood from B‐type blood.
Journals
2025 EN
SastournéHaletou Romain · Marynberg Sacha · Pereira Arthur
+23 more
This symposium is the 6th Paris Sciences & Lettres (PSL) Chemical Biology meeting (2015, 2016, 2019, 2023, 2024, 2025) being held at Institut Curie. This initiative originally started in 2013 at Institut de Chimie des Substances Naturelles (ICSN) in Gif‐sur‐Yvette and was mostly focused on organic synthesis. It was then exported at Institut Curie to cover a larger scope, before becoming the official French Chemical Biology meeting. This year, around 200 participants had the opportunity to meet world leaders in chemistry and biology who described their latest innovations and future trends covering topics as diverse as prebiotic chemistry, activity‐based protein profiling, high‐resolution cell imaging, nanotechnologies, bio‐orthogonal chemistry, metal ion signaling, ferroptosis, and biocatalysis.
Journals
2025 EN
Möller Christina · Pohlschröder Fabian · Wesche Jan
+9 more
The transfusion of blood products requires ABO compatibility due to A and B antigens on blood cells and their corresponding antibodies in plasma. The supply of red cell concentrates (RCCs) and platelet concentrates (PCs) is challenged by rising demand and declining numbers of donors. To counteract the supply limitations, a method is developed to generate universal RCCs and PCs. For this, the A antigen is enzymatically removed by two enzymes from Flavonifractor plautii working in concert and the B antigen is removed by galactosidases from Pedobacter panaciterrae (PpaGal_WT or the variant PpaGal_W260Y) and Akkermansia muciniphila (AmGH110A or AmGH110B). The glycosidases are immobilized on polymethacrylate microparticles and are removed by the 200 µm filter of the mandatory transfusion set before the transfusion to avoid a possible immune reaction by the enzymes. B‐positive red cells in RCCs are reduced below a 4% background signal within 48 h at 2–6 °C. Pooled PCs showed a 34 ± 14% reduction in B‐positive cells and a residual A‐positive platelet population of 4 ± 1% after 4 h of treatment at 20–24 °C. This approach efficiently generates ABO‐universal RCCs and PCs while preserving blood quality and reducing incompatibility risks.