Harnessing the inflammation and angiogenesis is extremely important in wound healing. In this study, we developed bioactive elastin-based hydrogels which can recruit and modulate the innate immune cells and accelerate angiogenesis in the wound site and subsequently improve wound regeneration. These hydrogels were formed by visible-light cross-linking of acryloyl-(polyethylene glycol)-N-hydroxysuccinimide ester modified elastin with methacrylated gelatin, in order to mimic dermal microenvironment. These hydrogels showed highly tunable mechanical properties, swelling ratios and enzymatic degradation profiles, with moduli within the range of human skin. To mimic the in vivo degradation of the elastin by elastase from neutrophils, in vitro co-culture of the hydrogels and neutrophils was conducted. The derived conditioned medium containing elastin derived peptides (EDP-conditioned medium) promoted the expression of both M1 and M2 markers in M1 macrophages in vitro. Additionally, the EDP-conditioned medium induced superior tube formation of endothelia cells in Matrigel. In mice wound model, these elastin-based hydrogels attracted abundant neutrophils and predominant M2 macrophages to the wound and supported their infiltration into the hydrogels. The outstanding immunomodulatory effect of the elastin-based hydrogels resulted in superior angiogenesis, collagen deposition and dermal regeneration. Hence, these elastin-based hydrogels can be a promising regenerative platform to accelerate wound repair.

Background: The effects of bone marrow mesenchymal stem cells (BMSCs) during the treatment of cartilage damage have been proven to be attributed to paracrine mechanisms, particularly the effect of exosomes. Exosomes from different batches are inhomogeneous, and different treatment effects are observed between samples. The purpose of this research was to find more effective and homogeneous exosomes for the repair of chondrocytes in osteoarthritis (OA). We observed the potential effects and possible mechanisms of exosomes derived from parathyroid hormone (PTH) (1-34)-preconditioned BMSCs (Exo^PTH) in the alleviation of OA. Materials and methods: Exosomes derived from BMSCs (Exo^BMSC) and Exo^PTH were isolated by differential centrifugation. Primary rat chondrocytes were used to establish the OA model by interleukin 1 beta (IL-1β) in vitro. The effects of these two types of exosomes on OA chondrocyte proliferation, migration, apoptosis, and extracellular matrix formation were measured and compared. We observed changes in IL-2, TNF-α, and IL-6 levels via Western blotting (WB), and quantitative real-time PCR (qRT–PCR). Results: We successfully extracted Exo^BMSC and Exo^PTH and established an IL-1β-induced OA model in primary chondrocytes from rats. Our study showed that IL-2, TNF-α, and IL-6 levels increased significantly in OA chondrocytes; however, both Exo^BMSC and Exo^PTH reduced the levels of IL-2, TNF-α, and IL-6. In addition, Exo^PTH exhibited stronger anti-inflammatory effects. Exo^PTH had a more marked effect on proliferation, migration, and production of the extracellular matrix (Col-II) in OA chondrocytes than Exo^BMSC at 24 h. Conclusion: Exo^PTH increased the migration, proliferation, and chondral matrix formation of OA chondrocytes in vitro. In OA chondrocyte therapy, the potential mechanism of Exo^PTH might involve the inhibition of production of proinflammatory cytokines. Although the two types of exosomes had some similar effects, most effects of Exo^PTH were better than those of Exo^BMSC, so Exo^PTH may have a better ability to alleviate OA.

Objective: Sepsis is the leading cause of death in patients admitted to adult intensive care units (ICUs). We aimed to determine the predictive value of red blood cell distribution width (RDW) in patients with sepsis in a large cohort. Methods: This retrospective observational study used data from the eICU Collaborative Research Database. The prognostic value of RDW was investigated using the receiver operating characteristic (ROC) curve, multiple logistic regression model, integrated discriminatory index (IDI), and net reclassification index (NRI). Results: In total, 9743 patients were included. The area under the ROC curve of the RDW for predicting hospital mortality was 0.631 (95% confidence interval [CI]: 0.616–0.645). Based on the multiple logistic regression model, an RDW of ≥14.5% was correlated with hospital mortality, regardless of Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scores (odds ratio [OR]: 1.838, 95% CI: 1.598–2.119). Using SOFA and APACHE IV scores as reference, the IDI and continuous NRI of RDW for hospital mortality was about 0.3 and 0.014, respectively. Conclusions: The RDW may be useful in predicting hospital mortality in patients with sepsis, offering extra prognostic value beyond SOFA and APACHE IV scores.

Sepsis remains a leading global cause of morbidity and mortality among the critically ill, driven by a dysregulated host response to infection that culminates in systemic inflammation and multi-organ dysfunction. While numerous potential biomarkers have been identified, their translation into robust clinical tools remains challenging. This review synthesizes the current understanding of sepsis biomarkers, focusing on their utility in delineating the intricate pathophysiological mechanisms underlying this heterogeneous syndrome and predicting patient outcomes. Crucially, we emphasize the pivotal role of cutting-edge methodologies, including advanced multi-omics integration, sophisticated bioinformatics, and machine learning algorithms, in accelerating the discovery and validation of novel precision-guided strategies. Through this synthesis, we outline recent advances and remaining knowledge gaps, aiming to inform precision medicine frameworks by highlighting how innovative technologies are reshaping the approach to biomarker identification and clinical application.

Cardiac arrest is a global health concern with consistently high mortality. It is also a common condition seen in the intensive care unit (ICU). We aimed to investigate the importance of albumin level on admission, which is a widely available and simple test, to predict in-hospital mortality in cardiac arrest patients. The retrospective study collected data from the eICU Collaborative Research Database. It contains data from 171 hospitals, 276 ICU wards, and 4,529 patients who were treated for cardiac arrest from 2014 to 2015. We analyzed the patients’ laboratory results and vital signs during the first 24 hours after admission to the ICU. The primary outcome was in-hospital mortality, and the secondary outcome was the length of ICU stay among survivors. In total, 2,414 patients were eligible. After adjusting for severity scores, including the Acute Physiology and Chronic Health Evaluation (APACHE) IV and Sequential Organ Failure Assessment (SOFA) scores, serum albumin was found to be a protective factor for survival (odds ratio of mortality: 0635, 95% confidence interval: 0.458-0.734, P<0.001). Among patients who survived until discharge, those with hypoalbuminemia had a long duration of stay in the ICU (P=0.005). The higher albumin level at admission to the ICU was associated with lower mortality in patients with cardiac arrest.

Regional citrate anticoagulation (RCA) is recommended for critically ill patients at high bleeding risk undergoing continuous renal replacement therapy (CRRT). Nafamostat mesylate (NM), a short-half-life serine protease inhibitor, is a popular alternative in East Asia. Direct comparisons of their efficacy and safety are limited. This retrospective single-center study included 81 critically ill patients receiving CRRT with either NM (n = 31) or RCA (n = 50) from January 2022 to January 2023. The primary outcome was filter lifespan. Secondary outcomes included circuit patency, bleeding events, and metabolic complications. The median filter lifespan was significantly shorter in the NM group compared to the RCA group (23.4 vs. 29.6 h, p = 0.02). The NM group also had a higher rate of unplanned circuit discontinuation (52.3 vs. 39.1%, p = 0.03). Multivariable analysis confirmed RCA was independently associated with a lower risk of circuit failure (HR = 0.44, p = 0.03). Although not statistically significant, trends favored NM regarding metabolic safety, with lower incidences of severe metabolic alkalosis (16.1 vs. 36.0%, p = 0.09) and hypocalcemia (9.7 vs. 26.0%, p = 0.13). RCA demonstrated superior anticoagulation efficacy in prolonging filter survival, while NM may offer a more favorable metabolic safety profile. The choice of anticoagulant should be individualized based on efficacy priorities and metabolic risk.