External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab.

OBJECTIVE: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy). DESIGN: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE). RESULTS: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively). CONCLUSION: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal. TRIAL REGISTRATION NUMBER: NCT00571337 and NCT02177071.

Thiol-polyethylene glycol-folic acid (HS-PEG-FA) induced aggregation of Au@Ag nanoparticles: A SERS and extinction UV-Vis spectroscopy combined study.

Plasmonic colloidal nanoparticles (NPs) functionalised with polymers are widely employed in diverse applications, offering advantages demonstrated over non-functionalised NPs such as enhanced colloidal stability or increased biocompatibility. However, functionalisation with polymers does not always increase the stability of the colloidal system. This work explores the intricate relationship between the functionalisation of plasmonic core@shell Au@Ag nanoparticles (NPs) with thiol-polyethylene glycol-folic acid (HS-PEG-FA) polymer chains and the resulting stability and spectral characteristics of Surface-Enhanced Raman Scattering (SERS) nanotags based on these NPs. We demonstrate that varying levels of HS-PEG-FA grafting influence nanotag stability, with a low level of grafting causing aggregation and subsequently affecting the spectral signature of Raman-reporter molecules attached to the surface of the NP. Electrostatic destabilisation is identified as the primary mechanism driving aggregation, impacting the SERS spectrum of Malachite Green isothiocyanate (MGITC) whose spectral shape is different between the aggregated and non-aggregated NPs. The findings provide valuable insights into NPs stability under different conditions, offering essential considerations for the design and optimisation of SERS nanotags in bio-analytical applications, particularly those involving data processing based on spectral shape, such as in multiplex approaches where experimental spectra are decomposed with several reference components.

Serum proteome signatures associated with ileal and colonic ulcers in Crohn's disease.

At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (n = 23), isolated ileal ulcers (n = 17), or isolated colonic ulcers (n = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (p-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location. SIGNIFICANCE: Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (n = 23); 2) isolated ileal ulcers (n = 17); 3) isolated colonic ulcers (n = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location.

Designing SERS nanotags for profiling overexpressed surface markers on single cancer cells: A review.

This review focuses on the chemical design and the use of Surface-Enhanced Raman Scattering (SERS)-active nanotags for measuring surface markers that can be overexpressed at the surface of single cancer cells. Indeed, providing analytical tools with true single-cell measurements capabilities is capital, especially since cancer research is increasingly leaning toward single-cell analysis, either to guide treatment decisions or to understand complex tumor behaviour including the single-cell heterogeneity and the appearance of treatment resistance. Over the past two decades, SERS nanotags have triggered significant interest in the scientific community owing their advantages over fluorescent tags, mainly because SERS nanotags resist photobleaching and exhibit sharper signal bands, which reduces possible spectral overlap and enables the discrimination between the SERS signals and the autofluorescence background from the sample itself. The extensive efforts invested in harnessing SERS nanotags for biomedical purposes, particularly in cancer research, highlight their potential as the next generation of optical labels for single-cell studies. The review unfolds in two main parts. The first part focuses on the structure of SERS nanotags, detailing their chemical composition and the role of each building block of the tags. The second part explores applications in measuring overexpressed surface markers on single-cells. The latter encompasses studies using single nanotags, multiplexed measurements, quantitative information extraction, monitoring treatment responses, and integrating phenotype measurements with SERS nanotags on single cells isolated from complex biological matrices. This comprehensive review anticipates SERS nanotags to persist as a pivotal technology in advancing single-cell analytical methods, particularly in the context of cancer research and personalized medicine.

Dynamics of leaching of POPs and additives from plastic in a Procellariiform gastric model: Diet- and polymer-dependent effects and implications for long-term exposure.

Procellariiform seabirds are known to have high rates of plastic ingestion. We investigated the bioaccessibility of plastic-associated chemicals [plastic additives and sorbed persistent organic pollutants (POPs)] leached from plastic over time using an in vitro Procellariiform gastric model. High-density polyethylene (HDPE) and polyvinyl chloride (PVC), commonly ingested by Procellariiform seabirds, were manufactured with one additive [decabrominated diphenyl ether (PBDE-209) or bisphenol S (BPS)]. HDPE and PVC added with PBDE-209 were additionally incubated in salt water with 2,4,4'-trichloro-1,1'-biphenyl (PCB-28) and 2,2',3,4,4',5'-hexachlorobiphenyl (PCB-138) to simulate sorption of POPs on plastic in the marine environment. Our results indicate that the type of plastic (nature of polymer and additive), presence of food (i.e., lipids and proteins) and gastric secretions (i.e., pepsin) influence the leaching of chemicals in a seabird. In addition, 100% of the sorbed POPs were leached from the plastic within 100 hours, while only 2-5% of the additives were leached from the matrix within 100 hours, suggesting that the remaining 95% of the additives could continue to be leached. Overall, our study illustrates how plastic type, diet and plastic retention time can influence a Procellariform's exposure risk to plastic-associated chemicals.