PYCR2 promotes growth and aerobic glycolysis in human liver cancer by regulating the AKT signaling pathway.

Hepatocellular carcinoma (HCC) is the world's third most fatal cancer. Because metabolic rewiring is a hallmark of HCC, studies into the causes of aberrant glycolysis could provide insight into novel HCC therapeutic strategies. Pyrroline-5-carboxylate reductase 2 (PYCR2), a key enzyme of proline synthesis, has previously been found to play vital roles in various malignancies regarding amino acid metabolism and oxidative stress response. Our study investigated the mechanistic function of PYCR2 in HCC. We used Gene Expression Profiling Interactive Analysis to perform bioinformatics analysis of PYCR2 expression and survival in human HCC patients based on the Cancer Genome Atlas database. The function of PYCR2 in cell viability and glycolysis was assessed using CCK-8 and ECAR assays. Transducing shRNA or overexpression vectors into the HCC cell line altered the expression status of PYCR2. PYCR2 expression was validated using quantitative real-time PCR and Western blot. In mouse xenograft models, the role of PYCR2 in HCC tumor formation was confirmed. PYCR2 was overexpressed in human HCC tumor tissue and was associated with a poor prognosis. The functional assay revealed that silencing PYCR2 inhibited cell viability, glycolysis, and AKT activation. Furthermore, the xenograft experiment demonstrated that silencing PYCR2 significantly inhibited tumor growth and Ki67 expression. On the other hand, PYCR2 overexpression significantly promoted cell viability and glycolysis, which could be inhibited by either a glycolysis inhibitor or an AKT inhibitor, indicating that PYCR2 may function via glycolysis and the AKT pathway. Moreover, despite the overexpression of PYCR2 in vivo, treatment with a glycolysis inhibitor may considerably suppress tumor growth. Our findings suggest that PYCR2 may play an oncogenic role in HCC growth by promoting glycolysis and activating AKT, emphasizing PYCR2's clinical relevance in HCC management as a novel potential therapeutic target.

Liver failure caused by intravenous amiodarone and effective intervention measures: A case report.

WHAT IS KNOWN AND OBJECTIVE: We present a case of intravenous amiodarone-induced liver injury, pharmacy monitoring and its therapy. CASE SUMMARY: A 76-year-old male patient developed acute liver injury 24 h after starting intravenous amiodarone. His liver enzymes improved after discontinuing amiodarone and anti-inflammatory liver therapy, which used reduced glutathione, magnesium isoglycyrrhizinate and ademetionine1,4-butanedisulfonate for injection. WHAT IS NEW AND CONCLUSION: Amiodarone is a highly effective antiarrhythmic agent for the treatment and prevention of atrial and ventricular arrhythmias. Acute liver damage after intravenous amiodarone is rare but potentially harmful. Amiodarone loading should be adapted to the necessity of an immediate effect of the drug, and liver function should be monitored closely in critically ill patients. Timely stopped suspected drug and anti-inflammatory liver therapy may reduce the occurrence of drug-induced diseases.

Detection of Acute Myocardial Infarction in a Pig Model Using the SAN-Atrial-AVN-His (SAAH) Electrocardiogram (ECG), Model PHS-A10, an Automated and Integrated Signals Recognition System.

BACKGROUND The aim of this study was to compare the use of the standard 12-lead electrocardiogram (ECG) with the SAN-Atrial-AVN-His (SAAH) ECG (Model PHS-A10), a new automated and integrated signals recognition system that detects micro-waveforms within the P, QRS, and T-wave, in a pig model of acute myocardial infarction (MI). MATERIAL AND METHODS Six medium-sized domestic Chinese pigs underwent general anesthesia, and an angioplasty balloon was placed and dilated for 120 minutes in the first diagonal coronary artery arising from the left anterior descending (LAD) coronary artery. A standard ECG and a SAAH ECG (Model PHS-A10) were used to evaluate: 1) the number of wavelets in ST-T segment in lead V5; 2) the duration of the repolarization initial (Ri), or duration of the wavelets starting from the J-point to the endpoint of the wavelets in the ST interval; 3) the duration of the repolarization terminal (Rt), of the wavelets, starting from the endpoint of the wavelets in the ST interval to the cross-point of the T-wave and baseline; 4) the ratio Ri: Rt. RESULTS Following coronary artery occlusion, duration of Ri and Ri/Rt increased, and Rt decreased, which was detected by the SAAH ECG (Model PHS-A10) within 12 seconds, compared with standard ECG that detected ST segment depression at 24 seconds following coronary artery occlusion. CONCLUSIONS The findings from this preliminary study in a pig model of acute MI support the need for clinical studies to evaluate the SAAH ECG (Model PHS-A10) for the early detection of acute MI.