Acute kidney injury (AKI) is one of the most common and severe clinical renal syndromes with high morbidity and mortality. Ferroptosis is a form of programmed cell death (PCD), is characterized by iron overload, reactive oxygen species accumulation, and lipid peroxidation. As ferroptosis has been increasingly studied in recent years, it is closely associated with the pathophysiological process of AKI and provides a target for the treatment of AKI. This review offers a comprehensive overview of the regulatory mechanisms of ferroptosis, summarizes its role in various AKI models, and explores its interaction with other forms of cell death, it also presents research on ferroptosis in AKI progression to other diseases. Additionally, the review highlights methods for detecting and assessing AKI through the lens of ferroptosis and describes potential inhibitors of ferroptosis for AKI treatment. Finally, the review presents a perspective on the future of clinical AKI treatment, aiming to stimulate further research on ferroptosis in AKI.

Prostate cancer (PCa) is the most common cancer among men in the United States and the leading cause of cancer-related death. The Solute Carrier Family 14 Member 1 (SLC14A1) is a member of urea transporters which are important for the regulation of urine concentration. However, the physiological significance of SLC14A1 in PCa still remains unclear. In the present study, via bioinformatics analysis and experiments, we found that expression of SLC14A1 is significantly decreased in PCa progression, which could be attributed to hypermethylation on SLC14A1 promoter region. Moreover, its low expression and hypermethylation on SLC14A1 promoter are closely related to the poor prognosis of PCa patients. On the other hand, overexpression of SLC14A1 inhibited cell proliferation and metastasis while its overexpression also suppressed CDK1/CCNB1 pathway and mTOR/MMP-9 signaling pathway. Additionally, SLC14A1 expression is enriched in prostate basal-type cells. In summary, our study indicates that its low expression level and promoter hypermethylation of SLC14A1 may represent novel indicators for PCa progression and prognosis, and SLC14A1 could inhibit the progression of PCa.

OBJECTIVE: To investigate the incidence and risk factors of acute kidney injury (AKI) stage 3 in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support.
METHODS: A retrospective case-control study.
METHODS: Single center, Fuwai Hospital.
METHODS: Adult VA-ECMO patients age ≥18 years and older treated between January 2020 and December 2022 were included.
METHODS: The patients were grouped by whether they developed AKI Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 or <3. Multivariate logistic regression was performed t\"o evaluate risk factors of AKI stage 3.
RESULTS: Among enrolled patients, 40 (53.3%) developed AKI stage 3. The in-hospital mortality of AKI stage 3 patients was significantly higher than that of AKI stage <3 patients (67.5% vs 34.3%; p = 0.004). Multivariate logistic regression analysis revealed that concomitant hypertension (odds ratio [OR], 0.250; 95% confidence interval [CI], 0.063, 0.987), p = 0.048), pre-ECMO hemoglobin (OR, 0.969; 95% CI, 0.947-0.992; p = 0.009), pre-ECMO lactate (OR, 1.173; 95% CI, 1.028-1.339; p = 0.018), and pre-ECMO creatinine (OR, 1.014; 95% CI, 1.003-1.025; p = 0.011) were independent risk factors for AKI stage 3.
CONCLUSIONS: This study found a high incidence (53.3%) of AKI stage 3 in adult patients with VA-ECMO support and an association with increased in-hospital mortality. Concomitant hypertension, low pre-ECMO hemoglobin, and elevated pre-ECMO lactate and pre-ECMO creatinine were independent risk factors for AKI stage 3 in patients receiving VA-ECMO. It is imperative to identify and adjust these risk factors to enhance outcomes for those supported by VA-ECMO.

暂无摘要。

Transcription factors (TFs) are essential proteins regulating gene expression by binding to specific nucleotide sequences upstream of genes. Among TF families, the forkhead box (FOX) proteins, characterized by a conserved DNA-binding domain, play vital roles in various cellular processes, including cancer. The FOXA subfamily, encompassing FOXA1, FOXA2, and FOXA3, stands out for its pivotal role in mammalian development. FOXA1, initially identified in the liver, exhibits diverse expression across multiple organ tissues and plays a critical role in cell proliferation, differentiation, and tumor development. Its structural composition includes transactivation domains and a DNA-binding domain, facilitating its function as a pioneer factor, which is crucial for chromatin interaction and the recruitment of other transcriptional regulators. The involvement of FOXA1 in sex hormone-related tumors underscores its significance in cancer biology. This review provides an overview of multifaceted roles of FOXA1 in normal development and its implications in the pathogenesis of hormone-related cancers, particularly breast cancer and prostate cancer.

The secretory leukocyte protease inhibitor (SLPI) is mainly produced by immune cells and various epithelial cells, and is regulated by a variety of cytokines, such as transforming growth factor β1, interleukin 1β and tumor necrosis factor α. In addition to commonly known anti-protease activity, it has been found in recent years that SLPI plays essential roles in anti-apoptosis, regulating cell cycle, cell differentiation and proliferation, and inhibiting inflammatory response. SLPI can also assist the immune system to clear pathogens/damaged cells by enhancing the phagocytic function of phagocytes, so as to ameliorate tissue damage and promote repair. Moreover, recent studies have shown that the change of SLPI level in the serum of patients post cardiovascular surgery has a high diagnostic value in predicting the occurrence of acute kidney injury, suggesting that SLPI is involved in ischemia-reperfusion (IR) induced acute kidney injury. In this review, we summarized the expression, regulation, signaling pathways and associated biological events of SLPI in different organ injury models, and also discussed and evaluated the potential role of SLPI in renoprotection against IR induced acute kidney injury and its potential as a new biomarker.

UNASSIGNED: Serum ferritin (SF) is clinically found to be elevated in many disease conditions, and our research examines serum ferritin in patients with acute kidney injury (AKI) and its implication on the risk of short-term mortality in AKI.
UNASSIGNED: Data were extracted from the Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2) database. Adult patients with AKI who had serum ferritin tested on the first day of ICU admission were included. The primary outcome was 28-day mortality. Kaplan-Meier survival curves and Cox proportional hazards models were used to test the relationship between SF and clinical outcomes. Subgroup analyses based on the Cox model were further conducted.
UNASSIGNED: Kaplan-Meier survival curves showed that a higher SF value was significantly associated with an enhanced risk of 28-day mortality, 90-day mortality, ICU mortality and hospital mortality (log-rank test: p < 0.001 for all clinical outcomes). In multivariate Cox regression analysis, high level of SF with mortality was significantly positive in all four outcome events (all p < 0.001). This result remains robust after adjusting for all variables. Subgroup analysis of SF with 28-day mortality based on Cox model-4 showed that high level of SF was associated with high risk of 28-day mortality in patients regardless of the presence or absence of sepsis (p for interaction = 0.730). Positive correlations of SF and 28-day mortality were confirmed in all other subgroups (p for interaction>0.05).
UNASSIGNED: High level of SF is an independent prognostic predictor of 28-day mortality in patients with AKI.

BACKGROUND Sepsis-associated acute kidney injury (SA-AKI) is linked to high mortality rates and an unfavorable prognosis. Early identification of patients with poor prognosis is crucial. This study aimed to investigate the relationship between the systemic immune-inflammation index (SII) and mortality in this specific patient population. MATERIAL AND METHODS This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV database. Data on patient demographics, comorbidities, vital signs, laboratory parameters, treatment usage, acute kidney injury staging, and renal replacement therapy were collected within 48 h of intensive care unit admission. Restricted cubic splines, Kaplan-Meier curves, and Cox regression models were used for analysis. Stratified analyses were performed on the basis of various factors. RESULTS In total, 7856 patients were included, with a median age of 66.9 years and a male-to-female ratio of 57.7%-42.3%. A J-shaped relationship was observed between SII and mortality risk. The lowest mortality risk occurred at an SII of 760.078×10⁹/L. Compared to the reference group (second quartile of SII), the highest and third quartiles had increased 28-day mortality risk, with adjusted hazard ratios (HRs) of 1.33 (1.16-1.52) and 1.55 (1.36-1.77), respectively. Although a trend towards higher mortality hazard was observed in the lowest SII group (Q1), it was not statistically significant, with an adjusted HR of 1.15 (1-1.32). CONCLUSIONS In patients with SA-AKI, both low and high SII were associated with increased short-term mortality risk. The lowest mortality risk was observed at an SII of 760.078×10⁹/L within a 28-day period.

BACKGROUND: Although it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are unclear.
METHODS: We assessed the causal relationship between prostatitis or BPH and PCa using a two-sample Mendelian randomization (MR) approach. The data utilized in this study were sourced from genome-wide association study. The association of genetic variants from cohorts of prostatitis or BPH and PCa patients was determined using inverse-variance weighted and MR Egger regression techniques. The direction of chance was determined using independent genetic variants with genome-wide significance (P < 5 × 10-6). The accuracy of the results was confirmed using sensitivity analyses.
RESULTS: MR analysis showed that BPH had a significant causal effect on PCa (Odds Ratio = 1.209, 95% Confidence Interval: 0.098-0.281, P = 5.079 × 10- 5) while prostatitis had no significant causal effect on PCa (P > 0.05). Additionally, the pleiotropic test and leave-one-out analysis showed the two-sample MR analyses were valid and reliable.
CONCLUSIONS: This MR study supports that BPH has a positive causal effect on PCa, while genetically predicted prostatitis has no causal effect on PCa. Nonetheless, further studies should explore the underlying biochemical mechanism and potential therapeutic targets for the prevention of these diseases.

Bone metastasis is an essential factor affecting the prognosis of prostate cancer (PCa), and circulating tumor cells (CTCs) are closely related to distant tumor metastasis. Here, the protein-protein interaction (PPI) networks and Cytoscape application were used to identify diagnostic markers for metastatic events in PCa. We screened ten hub genes, eight of which had area under the ROC curve (AUC) values > 0.85. Subsequently, we aim to develop a bone metastasis-related model relying on differentially expressed genes in CTCs for accurate risk stratification. We developed an integrative program based on machine learning algorithm combinations to construct reliable bone metastasis-related genes prognostic index (BMGPI). On the basis of BMGPI, we carefully evaluated the prognostic outcomes, functional status, tumor immune microenvironment, somatic mutation, copy number variation (CNV), response to immunotherapy and drug sensitivity in different subgroups. BMGPI was an independent risk factor for disease-free survival in PCa. The high risk group demonstrated poor survival as well as higher immune scores, higher tumor mutation burden (TMB), more frequent co-occurrence mutation, and worse efficacy of immunotherapy. This study highlights a new prognostic signature, the BMGPI. BMGPI is an independent predictor of prognosis in PCa patients and is closely associated with the immune microenvironment and the efficacy of immunotherapy.