FURIN suppresses the progression of atherosclerosis by promoting macrophage autophagy.

FURIN, a member of the mammalian proprotein convertases (PCs) family, can promote the proteolytic maturation of proproteins. It has been shown that FURIN plays an important role in the progression of atherosclerosis (AS). Current evidence indicates that autophagy widely participates in atherogenesis. This study aimed to explore whether FURIN could affect atherogenesis via autophagy. The effect of FURIN on autophagy was studied using aortic tissues from aortic dissection patients who had BENTALL surgery, as well as macrophages and ApoE-/- mice. In atherosclerotic plaques of aortic tissues from patients, FURIN expression and autophagy were elevated. In macrophages, FURIN-shRNA and FURIN-overexpression lentivirus were used to intervene in FURIN expression. The results showed that FURIN overexpression accelerated LC3 formation in macrophages during the autophagosome formation phase. Furthermore, FURIN-induced autophagy resulted in lower lipid droplet concentrations in macrophages. The western blot revealed that FURIN regulated autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway. In vivo, FURIN overexpression resulted in increased macrophage LC3 formation in ApoE-/- mice atherosclerotic plaques, confirming that FURIN could inhibit the progression of AS by promoting macrophage autophagy. The present study demonstrated that FURIN suppressed the progression of AS by promoting macrophage autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway, which attenuated atherosclerotic lesion formation. Based on this data, current findings add to our understanding of the complexity of AS.

STC2 is a potential biomarker of hepatocellular carcinoma with its expression being upregulated in Nrf1α-deficient cells, but downregulated in Nrf2-deficient cells.

Nrf1 (encoded by Nfe2l1) and Nrf2 (encoded by Nfe2l2), as two key members of the CNC-bZIP transcription factor, exhibit significant functional differences in their pathophysiology. Our previous findings demonstrated that loss of Nrf1α (i.e., a full-length isoform of Nrf1) promotes HepG2-derived tumor growth in xenograft mice, but malgrowth of the xenograft tumor is significantly suppressed by knockout of Nrf2. To gain insights into the mechanism underlying such marked distinctions in their pathologic phenotypes, we mined transcriptome data from liver cancer in the TCGA database to establish a prognostic model and calculate predicted risk scores for each cell line. The results revealed that knockout of Nrf1α markedly increased the risk score in HepG2 cells, whereas the risk score was reduced by knockout of Nrf2. Notably, stanniocalcin 2 (STC2), a biomarker associated with liver cancer, that is upexpressed in hepatocellular carcinoma (HCC) tissues with a reduction in the overall survival ratio of those patients. We observed increased expression levels of STC2 in Nrf1α-/- cells but decreased expression in Nrf2-/- cells. These findings suggested that STC2 may play a role in mediating the distinction between Nrf1α-/- and Nrf2-/-. Such potential function of STC2 was further corroborated through a series of experiments combined with transcriptomic sequencing. The results revealed that STC2 functions as a dominant tumor-promoter, because the STC2-leading increases in clonogenicity of hepatoma cells and malgrowth of relevant xenograft tumor were almost completely abolished in STC2-/- cells. Together, these demonstrate that STC2 could be paved as a potential therapeutic target, albeit as a diagnostic marker, for HCC.

ECM1 regulates the resistance of colorectal cancer to 5-FU treatment by modulating apoptotic cell death and epithelial-mesenchymal transition induction.

5-Fluorouracil (5-FU) chemoresistance is a persistent impediment to the efficient treatment of many types of cancer, yet the molecular mechanisms underlying such resistance remain incompletely understood. Here we found CRC patients resistant to 5-FU treatment exhibited increased extracellular matrix protein 1 (ECM1) expression compared to CRC patients sensitive to this chemotherapeutic agent, and higher levels of ECM1 expression were correlated significantly with shorter overall survival and disease-free survival. 5-FU resistant HCT15 (HCT15/FU) cells expressed significantly higher levels of ECM1 relative to parental HCT15 cells. Changes in ECM1 expression altered the ability of both parental and HCT15/FU cells to tolerate the medication in vitro and in vivo via processes associated with apoptosis and EMT induction. From a mechanistic perspective, knocking down and overexpressing ECM1 in HCT15/FU and HCT15 cell lines inhibited and activated PI3K/AKT/GSK3ß signaling, respectively. Accordingly, 5-FU-induced apoptotic activity and EMT phenotype changes were affected by treatment with PI3K/AKT agonists and inhibitors. Together, these data support a model wherein ECM1 regulates CRC resistance to 5-FU via PI3K/AKT/GSK3ß pathway-mediated modulation of apoptotic resistance and EMT induction, highlighting ECM1 as a promising target for therapeutic intervention for efforts aimed at overcoming chemoresistance in CRC patients.

In situ repair or reconstruction of the abdominal aorta-iliac artery by autologous fascia-peritoneum with posterior rectus sheath for the treatment of the infected abdominal aortic and iliac artery aneurysms: A case series and literature review.

Background: Infected abdominal aortic and iliac artery aneurysms are considered acute and severe diseases with insidious onset, rapid development, and high mortality in vascular surgery. Currently, there is no better treatment, either anatomic or extra-anatomical repair. Case presentation: From February 2018 to April 2022, 7 patients with infected abdominal aortic and iliac artery aneurysms did not have sufficient autologous venous material for repair. With the consent of the Ethics Committee of the hospital, it uses the autologous peritoneal fascial tissue with rectus sheath to repair or reconstruct the infected vessels in situ. There were 5 cases of infected abdominal aortic aneurysm, 1 case of an infected common iliac aneurysm, and 1 case of the infected internal iliac aneurysm. Aortoduodenal fistula was found in 3 cases, all of them were given duodenal fistula repair and gastrojejunostomy and cholecystostomy. Three cases of infected abdominal aortic aneurysms were repaired with the autologous peritoneal fascial tissue patch, and 2 cases of infected abdominal aortic aneurysms were reconstructed by the autologous peritoneal fascial tissue suture to bifurcate graft in situ, the autologous peritoneal fascial tissue suture reconstructed the rest 2 cases of infected iliac aneurysm to tubular graft in situ. It was essential that Careful debridement of all infected tissue and adequate postoperative irrigation and drainage. Antibiotics were administered perioperatively, and all patients were subsequently treated with long-term antibiotics based on bacterial culture and susceptibility results of infected tissues and blood. All 7 patients had underwent surgery successfully. But there were 2 cases died of anastomotic infection or massive hemorrhage after the operation, the other 5 cases survived. The follow-up time was 2-19 months. The enhanced CT of postoperation showed that the reconstructed arteries were smooth without obvious stenosis or expansion, and no abdominal wall hernia occurred. Conclusion: In situ repair or reconstruction with autologous peritoneal fascial tissue with rectus sheath is a feasible treatment for the infected aneurysm patients without adequate autologous venous substitute, but it still needs long-term follow-up and a large sample to be further confirmed.