Background: Few studies have studied the relationship between blood culture and mortality in sepsis patients. The aim of this study was to compare the characteristics and outcomes of positive and negative blood culture sepsis. Methods: We performed a study on 640 patients suffering from sepsis in Beijing Chao-Yang Hospital from October 2017 to December 2019. The primary findings revolved around length and expenditure of hospital stay, the possibility of suffering from acute respiratory distress syndrome (ARDS), and any requirements for mechanical ventilation. The secondary findings revolved around whether the patient died early (28-day) or late (28-to-90-day). Results: A total of 592 of the 640 patients met the inclusion criteria for sepsis, with 274 of them having culture-positive results. The culture-positive patients were mostly elderly suffering from diabetes and at risk of cancer, with a higher white blood cell count, and higher procalcitonin. Additionally, they scored higher in their acute physiology and chronic health evaluation II score (15 vs.11, P=0.010), as well as in their predisposition, infection, response, and organ dysfunction (17 vs 11, P< 0.001) than the individuals in the culture-negative group. Culture-positive patients had a longer duration of hospital stay (14 vs 6, P< 0.001) and higher in-hospital mortality (14.6% vs 8.5%, P=0.019) than culture-negative ones. No significant difference in intensive care unit (ICU) mortality (45.7% vs.36.4%, P=0.254) or early mortality (9.5% vs 7.2%, P=0.321) was noted between the two groups. However, the culture-positive patients had increased late mortality (15.7% vs.6.9%, P=0.001), when compared with those with culture-negative results in the cohort. Furthermore, the culture-positive patients who received the appropriate antibiotics early had a lower mortality rate than the culture-negative patients (7.3% vs.14.2%, P=0.008). Conclusion: Culture-positive patients had higher in-hospital mortality, comparable early mortality, and worse late mortality than the culture-negative patients. Early appropriate use of antibiotics might reduce mortality and improve clinical prognosis.

Liver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one‐directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications. Therefore, the aim of the present study was to investigate the role of HSCs on the inflammatory phenotype of KCs. Primary rat HSCs and KCs were isolated from male Wistar rats. HSCs‐derived conditioned medium (CM) was harvested from different time intervals (Day 0−2: CM‐D2 and Day 5−7: CM‐D7) during the activation of HSCs. Extracellular vesicles (EVs) were isolated from CM by ultracentrifugation and evaluated by nanoparticle tracking analysis and western blot analysis. M1 and M2 markers of inflammation were measured by quantitative PCR and macrophage function by assessing phagocytic capacity. CM‐D2 significantly induced the inflammatory phenotype in KCs, but not CM‐D7. Neither CM‐D2 nor CM‐D7 affected the phagocytosis of KCs. Importantly, the proinflammatory effect of HSCs‐derived CM is mediated via EVs released from HSCs since EVs isolated from CM mimicked the effect of CM, whereas EV‐depleted CM lost its ability to induce a proinflammatory phenotype in KCs. In addition, when the activation of HSCs was inhibited, HSCs produced less EVs. Furthermore, the proinflammatory effects of CM and EVs are related to activating Toll‐like receptor 4 (TLR4) in KCs. In conclusion, HSCs at an early stage of activation induce a proinflammatory phenotype in KCs via the release of EVs. This effect is absent in CM derived from HSCs at a later stage of activation and is dependent on the activation of TLR4 signaling pathway.

Coumarin derivates have been proposed as a potential treatment for metabolic-dysfunction-associated fatty liver disease (MAFLD). However, the mechanisms underlying their beneficial effects remain unclear. In the present study, we explored the potential of the coumarin derivate esculetin in MAFLD, focusing on hepatocyte lipotoxicity and lipid accumulation. Primary cultures of rat hepatocytes were exposed to palmitic acid (PA) and palmitic acid plus oleic acid (OA/PA) as models of lipotoxicity and lipid accumulation, respectively. Esculetin significantly reduced oxidative stress in PA-treated hepatocytes, as shown by decreased total reactive oxygen species (ROS) and mitochondrial superoxide production and elevated expression of antioxidant genes, including Nrf2 and Gpx1. In addition, esculetin protects against PA-induced necrosis. Esculetin also improved lipid metabolism in primary hepatocytes exposed to nonlipotoxic OA/PA by decreasing the expression of the lipogenesis-related gene Srebp1c and increasing the expression of the fatty acid β-oxidation-related gene Ppar-α. Moreover, esculetin attenuated lipid accumulation in OA/PA-treated hepatocytes. The protective effects of esculetin against lipotoxicity and lipid accumulation were shown to be dependent on the inhibition of JNK and the activation of AMPK, respectively. We conclude that esculetin is a promising compound to target lipotoxicity and lipid accumulation in the treatment of MAFLD.

Liver sinusoidal endothelial cells (LSECs) are key targets for addressing metabolic dysfunction-associated steatotic liver disease (MASLD). However, isolating and culturing primary LSECs is challenging due to rapid dedifferentiation, resulting in loss of function. The extracellular matrix (ECM) likely plays a crucial role in maintaining the fate and function of LSECs. In this study, we explored the influence of liver-ECM (L-ECM) on liver cells and developed culture conditions that maintain the differentiated function of liver cells in vitro for prolonged periods. Porcine liver-derived L-ECM, containing 34.9 % protein, 0.045 % glycosaminoglycans, and negligible residual DNA (41.2 ng/mg), was utilized to culture primary rat liver cells in generated hydrogels. Proteomic analyses and molecular weight distribution of proteins of solubilized L-ECM revealed the typical diverse ECM core matrisome, with abundant collagens. L-ECM hydrogels showed suitable stiffness and stress relaxation properties. Furthermore, we demonstrated that collagen-rich L-ECM hydrogels enhanced LSECs' and hepatocytes' viability, and reduced the dedifferentiation rate of LSECs. In addition, hepatocyte function was maintained longer by culture on L-ECM hydrogels compared to traditional culturing. These beneficial effects are likely attributed to the bioactive macromolecules including collagens, and mechanical and microarchitectural properties of the L-ECM hydrogels.

Oxidative stress is a key contributor to the onset and progression of diverse pathological conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD), neurodegeneration, cardiovascular disorders, and cancer. Conventional antioxidant therapies, such as small-molecule scavengers or systemic enzyme administration, are limited by poor stability, inefficient delivery, and off-target effects. Extracellular vesicles (EVs), particularly exosomes, are increasingly recognized as natural carriers of antioxidant enzymes (AOEs), including catalase, superoxide dismutases, glutathione peroxidases, peroxiredoxins, and thioredoxin. These vesicles not only protect enzymes from degradation but also enable targeted delivery to recipient cells, where they can actively modulate redox homeostasis. In this review, we summarize current evidence for AOEs as bona fide EV cargo, outline mechanisms that govern their selective packaging and transfer, and highlight their roles in intercellular communication under physiological and pathological conditions. We also discuss emerging therapeutic applications of both natural and engineered EVs for redox modulation, along with the challenges of quantifying enzymatic activity, ensuring reproducibility, and scaling clinical translation. By integrating insights from cell biology, redox signaling, and translational research, we propose that EV-mediated AOE delivery represents a promising next-generation strategy for combating oxidative stress-related diseases.