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To better understand diabetic nephropathy (DN), developing accurate animal models is crucial. Current models often fail to fully mimic human DN, showing only mild albuminuria, glomerular hypertrophy, and limited mesangial matrix expansion. Our study aims to develop a more robust model by combining streptozotocin (STZ)-induced diabetes with a high-protein diet (HPD). We divided C57Bl/6J mice into three groups: control, STZ with a standard diet (STZ-SD), and STZ with a HPD (45 kcal% protein) (STZ-HPD) for 12 weeks. Renal function was evaluated using the urinary albumin-to-creatinine ratio, and kidney tissues were analyzed for histological and molecular changes. The STZ-HPD group showed significantly higher albuminuria and more severe glomerular and tubular damage compared to the control and STZ-SD groups. These changes were accompanied by increased inflammatory and oxidative stress markers, highlighting the harmful effects of high-protein intake on renal injury. Our findings suggest that the STZ-HPD model could be a valuable tool for studying DN pathophysiology and evaluating therapeutic interventions, providing a new approach for preclinical research.

The success of cancer immunotherapy relies on the induction of an immunoprotective response targeting tumor antigens (TAs) presented on MHC-I molecules. We demonstrated that the splicing inhibitor isoginkgetin and its water-soluble and non-toxic derivative IP2 act at the production stage of the pioneer translation products (PTPs). We showed that IP2 increases PTP-derived antigen presentation in cancer cells in vitro and impairs tumor growth in vivo. IP2 action is long-lasting and dependent on the CD8+ T cell response against TAs. We observed that the antigen repertoire displayed on MHC-I molecules at the surface of MCA205 fibrosarcoma is modified upon treatment with IP2. In particular, IP2 enhances the presentation of an exon-derived epitope from the tumor suppressor nischarin. The combination of IP2 with a peptide vaccine targeting the nischarin-derived epitope showed a synergistic antitumor effect in vivo. These findings identify the spliceosome as a druggable target for the development of epitope-based immunotherapies.Darrigrand, Pierson et al. study the effect of mRNA splicing inhibitors on the generation of the MHC class I ligands. They developed a derivative of the spliceosome inhibitor isoginkgetin which is less toxic and more effective at enhancing antigen presentation and CD8+ T cell activation and showed greater antitumour activity in vivo. These findings identify the spliceosome as a druggable target for the development of epitope-based immunotherapies.

PurposeNeurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation.MethodsENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality.Results1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71–0.87] and 0.71 CI95 [0.61–0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7–21] vs 6 [3–11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure).ConclusionsIn neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.

Objectives To evaluate the technical assets of a new imaging device that, wifi linked to a AI based algorithm, automatically grades in vivo the exfoliating process of the skin, taking dandruff as model. Material and Methods The hand portable device comprises a camera that possibly uses three illuminating conditions (white LED diffused lamp, cross‐polarized white light and UVA rays). The learning phase of the algorithm was built on 3600 images of the vertex area of 234 subjects of different ages and three ethnicities with and without dandruff. This learning phase allowed 15 experts and dermatologists to score regarding a 6‐point atlas of dandruff severities, taken as reference. In a second validation phase, 460 images from 192 subjects of different ages and ethnic background/phototypes, were automatically analyzed by the AI based device, allowing to calculate the correlation between expert's assessments and the gradings provided by the device, and, as second indicator, to compute the Mean Average Error (MAE) between both variables. Results The values were found significantly correlated (r2 = 0.952; p < 0.001) with an overall MAE of 0.16 grading units, although presenting some differences according to ethnic background and phototypes (0.12–0.24). Conclusion This new imaging device coupled with AI‐based analysis allows a valid, rapid, and easy determination of the scalp exfoliating process and may represent a complementary help in the diagnosis of dermatologists in some other scalp disorders. Its versatility, easy handling, and immediate AI‐based analysis suggest that it may be applied to other cosmetic areas (skincare, makeup, haircare, etc.).