BackgroundExosomes derived from umbilical cord mesenchymal stem cells (UCMSC-Exos) have emerged as a highly promising cell-free therapeutic strategy for repairing acute kidney injury (AKI). However, preclinical evidence regarding their efficacy and optimal administration strategy remains heterogeneous and has not been systematically synthesized.MethodsPubMed, Web of Science, Embase, and Scopus were systematically searched to identify randomized controlled experiments evaluating UCMSC-Exos in rat models of AKI. Conventional meta-analyses were performed to pool effect sizes, and frequentist network meta-analyses were used to compare the relative efficacy and ranking probabilities of different interventions.ResultsFourteen studies were included. Conventional meta-analysis showed that, compared with controls, UCMSC-Exos significantly reduced serum creatinine (Scr; SMD = −5.60, 95% CI: −7.61 to −3.60) and blood urea nitrogen (BUN; SMD = −6.33, 95% CI: −8.91 to −3.75), alleviated renal histological injury scores (SMD = −3.62, 95% CI: −4.91 to −2.), and decreased cell apoptosis (SMD = −4.35, 95% CI: −6.06 to −2.64). Network meta-analysis further indicated that, at a fixed dose of 100 μg, tail vein injection was significantly superior to subcapsular renal injection in reducing Scr (SUCRA: 94.2% vs. 55.8%) and showed a similar trend for BUN. Within each administration route, distinct dose–response patterns were observed. For tail vein injection, there were no significant differences in efficacy among 30 μg, 100 μg, and 250 μg, although 100 μg showed the most favorable trend. In contrast, subcapsular renal injection exhibited a dose-dependent pattern, with higher doses (200 μg, 400 μg) being more effective than the lower 100 μg dose. Methodological reporting quality was generally inadequate, and potential publication bias was detected; however, the adjusted effect size remained statistically significant (SMD = −2.59).ConclusionUCMSC-Exos effectively improve renal function, histopathology, and cell survival in rat models of AKI. Tail vein injection, particularly at a dose of 100 μg, may represent the most effective strategy, whereas subcapsular renal injection may require higher doses to achieve adequate efficacy. These conclusions should be interpreted cautiously, and future studies should more rigorously control for and report potential confounders, such as animal sex and AKI induction methods.

Diffuse alveolar epithelial cell (AEC) death occurs extensively during acute lung injury (ALI). Due to the limited proliferative capacity of alveolar type 1 epithelial (AT1) cells, the differentiation and regenerative capacity of alveolar type 2 epithelial (AT2) cells are required to restore the barrier function of AECs. However, during lung injury, AT1 cells are particularly susceptible to injury, and ATII cells die in the presence of severe or certain types of injury. This disruption ultimately results in a hindrance to the ability of AT2 cells to proliferate and differentiate into AT1 cells in time to repair the extensively damaged AECs. Therefore, understanding the mechanism of injury death of AT2 cells may be beneficial to reverse the above situation. This article reviews the main death modes of AT2 cells, including apoptosis, necrosis, necroptosis, pyroptosis, autophagic cell death, and ferroptosis. It compares the various forms of death, showing that various cell injury death modes have unique action mechanisms and partially overlapping pathways. Studying the mechanism of AT2 cell death is helpful in screening and analyzing the target pathway of AEC barrier function recovery. It opens up new ideas and strategies for preventing and treating ALI.

IL-38, an anti-inflammatory cytokine, is a key regulator of homeostasis in host immunity. Intestinal immunity plays a critical role in defence against pathogenic invasion, as it is the largest surface organ and the most common entry point for micro-organisms. Dysregulated IL-38 activity is observed in several autoimmune diseases including systemic lupus erythematosus and atherosclerosis. The protective role of IL-38 is well illustrated in experimental colitis models, showing significantly worse colitis in IL-38 deficient mice, compared to wildtype mice. Moreover, exogenous IL-38 has been shown to ameliorate experimental colitis. Surprisingly, upregulated IL-38 is detected in inflamed tissue from inflammatory bowel disease patients, consistent with increased circulating cytokine levels, demonstrating the complex nature of host immunity in vivo. However, colonic IL-38 is significantly reduced in malignant tissues from patients with colorectal cancer (CRC), compared to adjacent non-cancerous tissue. Additionally, IL-38 expression in CRC correlates with 5-year survival, tumour size and differentiation, suggesting IL-38 plays a protective role during the development of CRC. IL-38 is also an independent biomarker for the prognosis of CRC, offering useful information in the management of CRC. Taken together, these data demonstrate the role of IL-38 in the maintenance of normal intestinal mucosal homeostasis, but that dysregulation of IL-38 contributes to initiation of chronic inflammatory bowel disease (resulting from persistent local inflammation), and that IL-38 provides protection during the development of colorectal cancer. Such data provide useful information for the development of novel therapeutic targets in the management of intestinal diseases for more precise medicine.

Abstract Background Gastric cancer is a malignant tumor with a high incidence and mortality rate. Angiogenesis is necessary for tumor infiltration and metastasis, and also affects patient prognosis. YKL-39 has monocyte chemotactic activity and pro-angiogenic activity in some of the tumors. In this study, we will investigate the relationship between YKL-39 and tumor-associated macrophages and microangiogenesis in gastric cancer and explore the value of YKL-39 as a prognostic biomarker for gastric cancer. Methods A total of 119 patients with gastric cancer who had undergone gastrectomy at the 940th Hospital of the Joint Security Force between 2013 and 2019 were included in this study, and the protein expression of YKL-39, CD68, and CD34 was detected by immunohistochemistry, and intracellular expression of YKL-39 and CD68 was detected by immunofluorescence. Results Our results showed that YKL-39 was expressed in both nucleus and cytoplasm of gastric cancer tissues and tumor mesenchyme, and the expression of YKL-39 was positively correlated with CD68 and CD34, as well as the high expression of YKL-39 was associated with poor prognosis of gastric cancer patients. Conclusion In gastric cancer, YKL-39 expression positively correlated with the degree of tumor-associated macrophage infiltration and angiogenesis, and it could be a potential prognostic marker and therapeutic target for gastric cancer.

Gastric cancer has a high incidence and mortality rate. Angiogenesis is necessary for tumor infiltration and metastasis and affects patient prognosis. YKL-39 has monocyte chemotactic activity and pro-angiogenic activity in some tumors. In this study, we investigated the relationship between YKL-39 and tumor-associated macrophages and microangiogenesis in gastric cancer to determine its potential as a prognostic biomarker. A total of 119 patients with gastric cancer who had undergone gastrectomy at the 940th Hospital of the Joint Security Force between 2014 and 2018 were included in this study. We assayed the protein expression of YKL-39, CD68, and CD34 by immunohistochemistry in tissues of 119 patients with gastric cancer, as well as the intracellular expression of YKL-39 and CD68 by immunofluorescence. Data were analyzed with SPSS Statistics 25.0 to explore the impact of expression of YKL-39, CD68, and CD34 in gastric cancer patients and the relationship among them. Our results show that YKL-39 was expressed in both the nucleus and cytoplasm of gastric cancer cells and tumor mesenchyme. YKL-39 protein expression was associated with the depth of tumor infiltration, lymph node metastasis, and TNM stage; CD68 protein expression was associated with lymph node metastasis and TNM stage; CD34 protein expression was not associated with clinicopathological characteristics. Expression of YKL-39 was positively correlated with CD68 and CD34 (p < 0.001), and high expression of YKL-39 was associated with poor prognosis (p < 0.05). In gastric cancer, YKL-39 expression is positively correlated with the degree of tumor-associated macrophage infiltration and angiogenesis, and is a potential prognostic marker for gastric cancer.