Mesenchymal stem cells (MSCs) have been studied for the treatment of acute liver failure (ALF) for several years. MSCs may exert their effect via complex paracrine mechanisms. Heme oxygenase (HO) 1, a rate-limiting enzyme in heme metabolism, exerts a wide range of anti-inflammatory, anti-apoptotic and immunoregulatory effects in a variety of diseases. However, the relationship between MSCs and HO-1 in the treatment of ALF is still unclear. We investigated the preventive and therapeutic potential of intravenously administered BMSCs. Bone marrow-derived mesenchymal stem cells (BMSCs) obtained from Sprague–Dawley rats were isolated and cultured. We employed BMSCs, hemin (a HO-1 inducer) and zinc protoporphyrin (ZnPP, the HO-1 activity inhibitor) in D-galactosamine (D-Gal)/lipopolysaccharides (LPS)-induced ALF rats. Rats were sacrificed at days 1, 3, 5, and 7 post-transfusion, respectively. Blood samples and liver tissues were collected. Hepatic injury, HO-1 activity, chemokines, inflammatory cytokines, the number and oxidative activity of neutrophils, ki67, and TUNEL-positive cells were evaluated. HO-1 induction or BMSCs transplantation attenuated D-galactosamine/lipopolysaccharide-induced increases in alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBIL), ammonia, and inflammatory cytokines. Treatment with hemin or BMSCs also inhibited neutrophil infiltration, oxidative activity, and hepatocyte apoptosis. The protective effect of BMSCs was partially neutralized by ZnPP, suggesting the key role of HO-1 in the process. These findings may correlate with inhibition of nuclear factor-κ B activation. BMSCs ameliorated ALF by increasing the HO-1 expression, which reduced PMN infiltration and function, and played an important anti-inflammatory and anti-apoptotic role. Proposed mechanism by which BMSCs reduce inflammation, neutrophil activation, and hepatocyte apoptosis and promote hepatocyte proliferation via HO-1. BMSCs increase HO-1 expression in liver via Nrf2. HO-1 protects against LPS/D-Gal-induced ALF by inhibiting neutrophil infiltration and inflammatory burst, and hepatocyte apoptosis and necrosis. HO-1 also promotes hepatocyte proliferation.

Pancreatitis is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). Previous studies in mice have demonstrated that pancreatitis contributes to oncogenic Kras‐driven carcinogenesis, probably initiated in acinar cells; however, oncogenic Kras alone or in combination with caerulein‐induced pancreatitis is not sufficient in initiating PDAC from the ductal compartment. We thus introduced ductal obstruction – which induces a more severe form of pancreatitis – by pancreatic ductal ligation in mice harbouring oncogenic Kras. This induced a particular phenotype with highly proliferative nonmucinous cells with nuclear atypia. Around these lesions, there was a significant proliferation of activated fibroblasts and infiltration of immune cells, corroborating the pathological features of preneoplastic lesions. Lineage‐tracing experiments revealed that these preneoplastic cells derived from two distinctive cellular sources: acinar and ductal cells. Phenotypic characterisation revealed that the duct‐derived preneoplastic lesions show a high proliferative potential with persistent activation of tumour‐promoting inflammatory pathways while the acinar‐derived ones were less proliferative with persistent p53 activation. Furthermore, the duct‐derived preneoplastic cells have a particularly high nuclear‐to‐cytoplasmic ratio. These data demonstrate that ductal obstruction promotes preneoplastic lesion formation from the pancreatic ductal compartment.

Ferroptosis has emerged as a potential therapeutic target in cancer. This study shows the critical role of AGR2 in ferroptosis suppression across pancreatic cancer cell lines and in vivo models. Notably, human pancreatic cancer cells exhibit dose-dependent AGR2 upregulation upon exposure to ferroptosis inducers. Genetic ablation of AGR2 significantly sensitizes cells to ferroptosis through a p53-mediated mechanism, while p53 knockdown effectively rescues ferroptosis resistance. Mechanistic investigations demonstrate that AGR2 deficiency activates p53 signaling, downregulating the iron exporter SLC40A1 (encoding ferroportin/FPN1), inducing intracellular iron overload and consequent ferroptosis. Clinically, we find a positive correlation between AGR2 and FPN1 expression in PDAC specimens, with co-elevation of both markers predicting unfavorable patient prognosis. Therapeutically, administration of an AGR2-targeting peptide synergizes with ferroptosis inducers, significantly enhancing cell death in PDAC models. Our findings not only elucidate a novel AGR2/p53/FPN1 regulatory axis in ferroptosis control but also propose innovative combination strategies for pancreatic cancer treatment.

Background Robotic surgery (RS) has gained increasing acceptance due to its ability to overcome certain limitations associated with laparoscopic surgery (LS). However, the performance of RS in hilar cholangiocarcinoma (HCCA) patients compared with LS remain unclear. This study aimed to compare the short- and long-term outcomes of RS versus LS in patients with HCCA. Method This retrospective study included patients who underwent radical resection of HCCA between February 2020 and August 2024. Baseline characteristics, pathological findings, surgical outcomes, and long-term outcomes were analyzed and compared between the RS and LS group. Results The baseline characteristics and pathologic findings of both groups were comparable. The RS group had less estimated blood loss [300 (175–400) vs 700 (200–750) ml, p = 0.008], and lower ALT, AST, TBIL, and DBIL compared to LS group, while no significant differences in postoperative complications. Regarding long-term outcomes, the overall survival rates and recurrence-free survival rates were comparable in two groups (p = 0.77 and p = 0.17, respectively). Conclusion This study demonstrated that robotic surgery for HCCA generally achieves satisfactory perioperative outcomes compared to laparoscopic surgery. With continued advancements in surgical techniques and accumulation of experience, robotic radical resection for HCCA could become a routine approach in the future.