Plasma metabolites as mediators in immune cell-pancreatic cancer risk: insights from Mendelian randomization.

Background: Immune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors. Methods: The genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites. Results: Our investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, ORIVW=1.105; 95% confidence interval, 95%CI: 1.002-1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (ORIVW=0.920; 95%CI: 0.873-0.968; P=0.001), and HLA DR+ CD8br T cells (ORIVW=1.058; 95%CI: 1.002-1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer. Conclusion: This MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.

A meta-analysis of Lactate Ringer's solution versus Normal Saline in the treatment of acute pancreatitis.

Fluid resuscitation is an important way in the treatment of acute pancreatitis (AP). This meta-analysis aimed to compare the safety and efficacy of Lactate Ringer's solution (LR) and Normal Saline (NS) in the treatment of patients with acute pancreatitis. Searched in PubMed, Web of Science Core Collection (Clarivate), Embase, Cochrane Library, CNKI, China Wanfang, and China VIP database. All randomized controlled clinical trials (RCTs) were identified. Six studies with 431 patients were included. Compared with NS, LR can significantly reduce the incidence of SIRS at 24h, reduce the length of hospitalization, moderate-severe AP, ICU admission and local complications, especially pancreatic necrosis. It is safe and effective to choose LR for fluid resuscitation in AP, but due to the small number of included studies, multi-center and large-sample RCTs are still needed for further verification. PROSPERO registration number: CRD42022322788.

UXT at the crossroads of cell death, immunity and neurodegenerative diseases.

The ubiquitous expressed transcript (UXT), a member of the prefoldin-like protein family, modulates regulated cell death (RCD) such as apoptosis and autophagy-mediated cell death through nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), P53, P62, and methylation, and is involved in the regulation of cell metabolism, thereby affecting tumor progression. UXT also maintains immune homeostasis and reduces proteotoxicity in neuro-degenerative diseases through selective autophagy and molecular chaperones. Herein, we review and further elucidate the mechanisms by which UXT affects the regulation of cell death, maintenance of immune homeostasis, and neurodegenerative diseases and discuss the possible UXT involvement in the regulation of ferroptosis and immunogenic cell death, and targeting it to improve cancer treatment outcomes by regulating cell death and immune surveillance.

The role of UXT in tumors and prospects for its application in hepatocellular carcinoma.

UXT is widely expressed in human and mouse tissues and aberrantly expressed in various tumor tissues. UXT may play a pro-cancer or tumor suppressor role in different tumor types and microenvironments with different mechanisms of action. Studies have shown that UXT can interact with related receptors to exert its functions and affect tumor proliferation and metastasis, leading to a poor prognosis when the biological functions of these tumors are changed. Interestingly, the signaling pathways and mechanism-related molecules that interact with UXT are closely related to the occurrence of hepatocellular carcinoma (HCC) during disease progression. This article reviews the research progress of UXT and prospects for its application in HCC, with the aim of providing possible scientific suggestions for the basic research, diagnosis and treatment of HCC.

Patients with hepatocellular carcinoma (HCC) have a poor overall prognosis. Surgical resection is the preferred treatment option for HCC; however, most patients are already in the middle and late stages of the disease at the time of diagnosis. Surgical resection cannot achieve a therapeutic effect, and targeted therapy has become a feasible alternative. In this review we summarize the expression and mechanisms of action of the protein UXT in a variety of tumors and discuss its potential for future development as a therapeutic target to further improve the targeted therapy of HCC.