Machine learning-based radiomics score improves prognostic prediction accuracy of stage II/III gastric cancer: A multi-cohort study.

BACKGROUND: Although accurately evaluating the overall survival (OS) of gastric cancer patients remains difficult, radiomics is considered an important option for studying prognosis. AIM: To develop a robust and unbiased biomarker for predicting OS using machine learning and computed tomography (CT) image radiomics. METHODS: This study included 181 stage II/III gastric cancer patients, 141 from Lichuan People's Hospital, and 40 from the Cancer Imaging Archive (TCIA). Primary tumors in the preoperative unenhanced CT images were outlined as regions of interest (ROI), and approximately 1700 radiomics features were extracted from each ROI. The skeletal muscle index (SMI) and skeletal muscle density (SMD) were measured using CT images from the lower margin of the third lumbar vertebra. Using the least absolute shrinkage and selection operator regression with 5-fold cross-validation, 36 radiomics features were identified as important predictors, and the OS-associated CT image radiomics score (OACRS) was calculated for each patient using these important predictors. RESULTS: Patients with a high OACRS had a poorer prognosis than those with a low OACRS score (P < 0.05) and those in the TCIA cohort. Univariate and multivariate analyses revealed that OACRS was a risk factor [RR = 3.023 (1.896-4.365), P < 0.001] independent of SMI, SMD, and pathological features. Moreover, OACRS outperformed SMI and SMD and could improve OS prediction (P < 0.05). CONCLUSION: A novel biomarker based on machine learning and radiomics was developed that exhibited exceptional OS discrimination potential.

Accurate in vivo real-time determination of the hydrogen concentration in different tissues of mice after hydrogen inhalation.

As an antioxidant, anti-inflammatory and anti-apoptotic agent, hydrogen (H2) shows a promising potential in basic and clinical research against various diseases owing to its safety and efficacy. However, knowledge involving its underlying mechanisms of action, dosage effects, and dose duration remains limited. Previously, the dynamics of H2 concentrations in different tissues of rats after exogenous H2 inhalation had been detected by our team. Here, sequential changes of H2 concentrations in different tissues of another most commonly used experimental rodent mice were monitored in real time with an electrochemical H2 gas sensor during continuous different concentrations of H2 inhalation targeting on five tissues including brain, liver, spleen, kidney, and gastrocnemius. The results showed that the H2 saturation concentrations varied among tissues significantly regardless of the concentration of H2 inhaled, and they were detected the highest in the kidney but the lowest in the gastrocnemius. Meantime, it required a significant longer time to saturate in the thigh muscle. By comparing the H2 saturation concentrations of mice and rats, we found that there were no differences detected in most tissues except the kidney and spleen. Both gas diffusion and bloodstream transport could help the H2 reach to most organs. The results provide data reference for dosage selection, dose duration determination to ensure optimal therapeutic effects of H2 for mice experiments.

Circ_0027089 regulates NACC1 by targeting miR-136-5p to aggravate the development of hepatitis B virus-related hepatocellular carcinoma.

Hepatitis B virus (HBV) infection is the main trigger of hepatocellular carcinoma (HCC). Circular RNA plays an indispensable role in cancer development, and this study aimed to disclose the function and mechanism of circ_0027089 in HBV-related HCC. The expression levels of circ_0027089, miR-136-5p and nucleus accumbens associated protein 1 (NACC1) mRNA were measured by quantitative real-time PCR, and the protein level of NACC1 was detected by western blot. For functional analyses, cell proliferation was assessed by cell counting kit-8 assay and colony formation assay. Cell apoptosis and cell cycle were detected by flow cytometry assay, and cell apoptosis was also assessed by caspase 3/7 activity. The capacities of migration and invasion were evaluated by wound healing assay and transwell assay, respectively. The predicted relationship between miR-136-5p and circ_0027089 or NACC1 was validated by dual-luciferase reporter assay and RNA binding protein immunoprecipitation assay. Animal experiments were performed in nude mice to explore the role of circ_0027089 in vivo. Circ_0027089 expression and NACC1 expression were elevated, while miR-136-5p expression was decreased in HBV-related HCC tissues and cells. In function, circ_0027089 knockdown inhibited HepG2.2.15 and HepAD38 (tet-off) cell proliferation, migration and invasion but induced cell cycle arrest and apoptosis, while circ_0027089 overexpression played the reversed effects. For mechanism exploration, miR-136-5p was a target of circ_0027089, and miR-136-5p deficiency could reverse the role of circ_0027089 knockdown. Circ_0027089 functioned as an oncogene to promote the development of HBV-related HCC by regulating NACC1 via competitively targeting miR-136-5p.

Apigenin Attenuates Adriamycin-Induced Cardiomyocyte Apoptosis via the PI3K/AKT/mTOR Pathway.

Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg-1), and high-dose API treatment group (250 mg·kg-1). Blood samples were taken to evaluate a spectrum of myocardial enzymes. Cardiomyocyte apoptosis was measured using a TUNEL assay, and cardiomyocyte autophagy was observed using electron microscopy. Moreover, apoptosis-related proteins, such as Bax and Bcl-2, autophagy-related proteins, including Beclin1 and LC3B, and PI3K/AKT/mTOR pathway-related proteins were examined with western blot. Our results demonstrate that ADR caused an increase in the serum levels of cardiac injury markers and enhanced cardiomyocyte apoptosis and autophagy. API administration prevented the effects associated with ADR-induced cardiotoxicity in mice and inhibited ADR-induced apoptosis and autophagy. API also promoted PI3K/AKT/mTOR pathway activity in ADR-treated mice. In conclusion, API may have a protective effect against ADR-induced cardiotoxicity by inhibiting apoptosis and autophagy via activation of the PI3K/AKT/mTOR pathway.

Curcumin Protects Neonatal Rat Cardiomyocytes against High Glucose-Induced Apoptosis via PI3K/Akt Signalling Pathway.

The function of curcumin on NADPH oxidase-related ROS production and cardiac apoptosis, together with the modulation of protein signalling pathways, was investigated in cardiomyocytes. Primary cultures of neonatal rat cardiomyocytes were exposed to 30 mmol/L high glucose with or without curcumin. Cell viability, apoptosis, superoxide formation, the expression of NADPH oxidase subunits, and potential regulatory molecules, Akt and GSK-3ß, were assessed in cardiomyocytes. Cardiomyocytes exposure to high glucose led to an increase in both cell apoptosis and intracellular ROS levels, which were strongly prevented by curcumin treatment (10 µM). In addition, treatment with curcumin remarkably suppressed the increased activity of Rac1, as well as the enhanced expression of gp91(phox) and p47(phox) induced by high glucose. Lipid peroxidation and SOD were reversed in the presence of curcumin. Furthermore, curcumin treatment markedly inhibited the reduced Bcl-2/Bax ratio elicited by high glucose exposure. Moreover, curcumin significantly increased Akt and GSK-3ß phosphorylation in cardiomyocytes treated with high glucose. In addition, LY294002 blocked the effects of curcumin on cardiomyocytes exposure to high glucose. In conclusion, these results demonstrated that curcumin attenuated high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH-mediated oxidative stress and this protective effect is most likely mediated by PI3K/Akt-related signalling pathway.