Search Results for: Scoperto nuovo biomarker per il cancro al colon-retto

Background
Early-onset gastric cancer (EOGC) is a lethal malignancy. It differs from late-onset gastric cancer (LOGC) in clinical and molecular characteristics. The current strategies for EOGC detection have certain limitations in diagnostic performance due to the rising trend in EOGC.

Objective
We developed a liquid biopsy signature for EOGC detection.

Design
We use a systematic discovery approach by analysing genome-wide transcriptomic profiling data from EOGC (n=43), LOGC (n=31) and age-matched non-disease controls (n=37) tissue samples. An extracellular vesicle-derived long non-coding RNA (EV-lncRNA) signature was identified in blood samples from a training cohort (n=299), and subsequently confirmed by qPCR in two external validation cohorts (n=462 and n=438), a preoperative/postoperative cohort (n=66) and a gastrointestinal tumour cohort (n=225).

Results
A three EV-lncRNA (NALT1, PTENP1 and HOTTIP) liquid biopsy signature was developed for EOGC detection with an area under the receiver operating characteristic curve (AUROC) of 0.924 (95% CI 0.889 to 0.953). This EV-lncRNA signature provided robust diagnostic performance in two external validation cohorts (Xi’an cohort: AUROC, 0.911; Beijing cohort: AUROC, 0.9323). Furthermore, the EV-lncRNA signature reliably identified resectable stage EOGC patients (stage I/II) and demonstrated better diagnostic performance than traditional GC-related biomarkers in distinguishing early-stage EOGC (stage I) from precancerous lesions. The low levels of this biomarker in postsurgery and other gastrointestinal tumour plasma samples indicated its GC specificity.

Conclusions
The newly developed EV-lncRNA signature effectively identified EOGC patients at a resectable stage with enhanced precision, thereby improving the prognosis of patients who would have otherwise missed the curative treatment window.

Basic scienceComing out of my (glyco)cage Ma W, Wang C, Kothandapani J, et al. Bespoke plant glycoconjugates for gut microbiota-mediated drug targeting. Science 2025; eadk7633. doi: 10.1126/science.adk7633. Targeted drug delivery to the colon is somewhat of a ‘holy grail’ in gastrointestinal medicine. The need to get the right drug to the right place at the right time to treat intestinal inflammation without the collateral damage of unwanted systemic uptake has led to several novel solutions over the years. These include multimatrix delivery systems, administration of prodrugs and pH-dependent and time-dependent carriers. Our ever-increasing knowledge of the human gut microbiota is allowing us to harness its activity to achieve the same ends. Xyloglucans (XyG) are polysaccharides found in fruit and vegetables. While humans lack enzymes to degrade XyG, human gut microbiomes all contain genes coding for these enzymes in abundant bacteria such as Bacteroides sp. In this study,…

Background
GPR171 suppresses T cell immune responses involved in antitumour immunity, while its role in inflammatory bowel disease (IBD) pathogenesis remains unclear.

Objective
We aimed to investigate the role of GPR171 in modulating CD4+ T cell effector functions in IBD and evaluate its therapeutic potential.

Design
We analysed GPR171 expression in colon biopsies and peripheral blood samples from patients with IBD and assessed the impact of GPR171 on CD4+ T cell differentiation through administration of its endogenous ligand (BigLEN). We further determined the role of GPR171 in dextran sulfate sodium (DSS)-induced colitis and CD45RBhighCD4+ T-cell transfer colitis model and deciphered the underlying mechanisms using RNA sequencing (RNA-seq) and lipidomics. We developed a novel BigLEN-based Fc fusion protein (BigLEN-Fc) and evaluated its potential in preventing and treating colitis.

Results
GPR171 was markedly increased in inflamed mucosa and CD4+ T cells of patients with IBD compared with controls. BigLEN-triggered GPR171 activation inhibited Th17 cell differentiation in vitro. GPR171 deficiency exacerbated DSS- and CD45RBhighCD4+ T cell-induced colitis in mice, characterised by increased Th17 cell responses in intestinal mucosa. Mechanistically, GPR171 deficiency promoted Th17 cell differentiation and altered lipidome profile in Th17 cells via the cAMP-pCREB-FABP5 axis. Blockage of FABP5 reduced Th17 cell differentiation in vitro and ameliorated DSS-induced colitis in Gpr171 –/– mice. Furthermore, BigLEN-mutFc administration potently mitigated colitis in mice.

Conclusions
GPR171 deficiency promotes Th17 cell differentiation and causes lipid metabolism perturbation, contributing to intestinal inflammation in a FABP5-dependent manner. Target therapy (eg, BigLEN-Fc) represents a novel therapeutic approach for IBD treatment.

Background
Gut microbial metabolites are recognised as critical effector molecules that influence the development of colorectal cancer (CRC). Peptidoglycan fragments (PGFs) produced by microbiota play a crucial role in maintaining intestinal homeostasis, but their role in CRC remains unclear.

Objective
Here, we aimed to explore the potential contribution of PGFs in intestinal tumourigenesis.

Design
The relative abundance of peptidoglycan synthase and hydrolase genes was assessed by metagenomic analysis. Specific PGFs in the faeces and serum of CRC patients were quantified using targeted mass spectrometry. The effects of PGF on intestinal tumourigenesis were systematically evaluated using various murine models of CRC and organoids derived from CRC patients. Downstream molecular targets were screened and evaluated using proteome microarray, transcriptome sequencing and rescue assays.

Results
Metagenomic analysis across seven independent cohorts (n=1121) revealed a comprehensive reduction in peptidoglycan synthase gene relative abundance in CRC patients. Targeted mass spectrometry identified significant depletion of a specific PGF, N-acetylmuramic acid (NAM) in CRC patients, which decreased as tumours progressed (p

Objective
A synthesis and appraisal of the recommendations for biomarkers in practice guidelines concerning sepsis is required to consolidate evidence-based practice. We generated an evidence gap map (EGM) on the use of biomarkers for managing adults with sepsis.

Design
Scoping review.

Data sources
MEDLINE, Guidelines International Network, Pan American Health Organization, Trip Database and UpToDate were searched from 2016 to March 2025.

Eligibility criteria
Guidance documents (GD) that searched at least one literature source and provided clinical recommendations for the use of biomarkers for the management (diagnosis and prognosis, including treatment response) of adults with sepsis.

Data extraction and synthesis
Two reviewers independently applied the eligibility criteria and extracted data. We used the AGREE-II (Appraisal of Guidelines for Research and Evaluation) tool to assess the GD quality. GDs that scored ≥50% on the AGREE-II ‘Rigour of development’ domain were considered robust. We also applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate if the recommendations were strong or conditional.

Results
We found 10 GDs, with only half (4/8) having a robust methodology. There were 31 recommendations concerning biomarkers. Among these, 24 (77.4%) recommendations were about single biomarkers, with lactate (23; 74.2%) and procalcitonin (8; 25.8%) most frequently recommended. Biomarker testing focused on prognosis in 28 (90.3%) recommendations. Overall, 16 (51.6%) recommendations were graded strong and 13 (42.0%) were conditional, which we displayed in an EGM.

Conclusions
The methodology of GDs concerning adult sepsis was poor. Our review calls for more prudent use of biomarkers in specific prognostic scenarios and in combination with standard clinical assessments. Enhancing the methodological quality of future GDs is essential to generate more valid and robust recommendations for optimising patient care.

A woman in her 50s with a history of hemochromatosis, psoriasis, and type 2 diabetes presented with a 3-month history of abdominal pain, weight loss, and a large palpable fixed abdominal mass. What is your diagnosis?

Agisce riducendo i livelli di molecole chiamate acidi biliari

Cellule cancerose modificano loro struttura per sfuggire farmaci

Tumore colon retto – Studio rileva presenza di microplastiche nei tessuti tumorali del colon-retto, aprendo interrogativi su salute umana e rischio oncologico.

Stroke, Ahead of Print. BACKGROUND:Spontaneous aneurysmal subarachnoid hemorrhage induces early blood-brain barrier permeability dysfunction, although its clinical relevance and underlying mechanisms remain poorly understood. We aimed to evaluate the association between blood-brain barrier disruption, quantified with dynamic contrast–enhanced magnetic resonance imaging at the end of the early brain injury period, circulating neuroinflammatory mediators, and long-term clinical outcomes.METHODS:We analyzed a prospective cohort of subarachnoid hemorrhage patients who underwent dynamic contrast–enhanced magnetic resonance imaging at a median (interquartile range) of 4 (2–6) days after clinical onset. Permeability maps were used to obtain K-trans values as a measure of increased blood-brain barrier permeability in the whole brain, gray matter, and white matter. Circulating neuroinflammatory molecules, including IL (interleukin) 8 and PDGF (platelet-derived growth factor), were measured using Multiplex-ELISA in blood samples collected concurrently with magnetic resonance imaging acquisition. Poor clinical outcome was defined as a modified Rankin Scale score of >2 at 90 days. Associations between K-trans values, neuroinflammatory mediators, and clinical outcomes were assessed using univariate and multivariate regression models.RESULTS:From 153 patients initially screened, 96 were finally included (63% females; median age, 55 years; 43% premorbid hypertension; 32% World Federation of Neurosurgical Societies grade 4–5; 31% poor outcome). In adjusted linear regression analyses, higher K-trans values were significantly associated with increased IL-8 (P=0.001) and PDGF (P=0.018) levels. In univariate analysis, K-trans values in white matter were significantly higher in patients with poor clinical outcome (median [interquartile range], 2.5 [2.07–6.09] ×10−3·min−1) compared with good clinical outcome (median [interquartile range], 2.0 [1.60–2.42] ×10−3·min−1;P

Stroke, Ahead of Print. Stroke significantly impacts mortality and long-term disability, necessitating effective rehabilitation strategies to enhance recovery. This review examines the roles of vagus nerve stimulation (VNS) and fastigial nucleus stimulation (FNS) in facilitating ischemic stroke recovery through brain-body interactions. VNS enhances ischemic stroke recovery by reprogramming microglia from proinflammatory (M1) to neuroprotective (M2) phenotypes, reducing neuroinflammation and promoting tissue repair via neurotrophic factors. It has shown promise in clinically improving chronic upper limb deficits when combined with rehabilitation therapies. Conversely, FNS provides cerebellar-mediated neuroprotection by mainly mitigating excitotoxic damage and inflammatory responses independent of cerebral blood flow alterations, as evidenced by preclinical models of middle cerebral artery occlusion. By integrating VNS-driven immunomodulation with FNS-mediated excitotoxicity suppression, this review highlights their synergistic potential to improve rehabilitation outcomes for ischemic stroke survivors. Biomarker-guided protocols: VNS for cortical/subcortical ischemic deficits and FNS for cerebellar network recovery are advocated to address postischemic disability via anti-inflammatory rewiring, neuroplasticity enhancement, and cerebellar-thalamocortical circuit stabilization. Critical gaps remain in hemorrhagic stroke, where FNS’s excitotoxicity suppression may destabilize clots, necessitating subtype-specific safety validations.

Background
Studies examining the association between Medicaid expansion (ME) under the Affordable Care Act (ACA) and colon cancer incidence have produced mixed results.

Objective
To re-visit the association between the ACA-ME and annual cases of colon cancer.

Design
Difference-in-differences (DiD).

Setting
The primary analyses used data from the National Cancer Database from 2010 to 2018, a hospital-based cancer registry in the USA. We also conducted exploratory analyses using data from the Surveillance, Epidemiology and End Results (SEER) registry.

Patients
Patients aged 40 and older with newly diagnosed colon cancer.

Measurements
The primary outcome was the percent change in colon cancer of all stages. Secondary outcomes were percent changes in stage I and stage IV cases.

Results
Among those aged 40–49, we observed a statistically significant greater increase in stage I colon cancer in expansion states relative to non-expansion states (DiD (percent change) 9.7% (95% CI, 2.5% to 17.4%)). In those aged 50–64, we did not observe statistically significant differences between the two state groups in any of the outcomes. Among those aged 65+, we observed a statistically significant relative decrease for all stages in ACA-ME states (–1.0% (95% CI, –1.0% to –3.0%)) and for stage IV (–3.0% (95% CI, –2.0% to –5.0%)). We explored our findings among younger individuals (

Oncologi, ‘è un cambio di paradigma significativo’

Consentirà di personalizzare cure sin dal momento della diagnosi