Upregulated X-C motif chemokine ligand 2 (XCL2) is associated with poor prognosis and increased immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most popular malignant carcinomas in the genitourinary system. As a novel tumor-related gene, X-C Motif Chemokine Ligand 2 (XCL2) was up-regulated in ccRCC. The current study aims to reveal the functional activity of XCL2 in ccRCC. METHODS: The transcriptome profiling, clinical parameters, and simple nucleotide variation profiles of ccRCC samples were obtained from the Cancer Genome Atlas (TCGA) database. The survival analysis, multivariate/univariate Cox analysis, correlation analysis, gene set enrichment analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Next, immune cell infiltration and immune functions were analyzed. Finally, the functions of XCL2 were investigated in Caki-1 and 786-O cells. RESULTS: Upregulated XCL2 was associated with worse overall survival of ccRCC and correlated to age, grade, stage, and T stage. Age, grade, and XCL2 were independent prognostic factors. Significant enrichment in apoptosis, DNA replication, and immune response was demonstrated by GSEA. XCL2 was not only tightly associated with immune cell infiltration, but also significantly linked with several immune functions. Moreover, patients, who had higher XCL2 expression, owned higher levels of TMB. Interestingly, XCL2 was positively correlated with common immune checkpoints. In vitro, XCL2 could inhibit apoptosis, and promote proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of Caki-1 and 786-O cells. CONCLUSIONS: In general, the current study suggested that XCL2 may participate in the progression of ccRCC. Importantly, XCL2 may be a potential new target of immunotherapy.

Value of layer-specific speckle tracking echocardiography for early detection of myocardial injury caused by chemotherapy in breast cancer patients with cardiovascular risk.

The probability of toxicity-related myocardial injury event with anthracyclines is controversial, which could be related to the underlying cardiac status before chemotherapy. Our study sought to investigate the influence of cardiovascular risk factors on myocardial motion and cardiac function using layer-specific speckle tracking echocardiography (STE) during chemotherapy with epirubicin. Female patients with first-diagnosed breast cancer were prospectively enrolled in our study and received 4 chemotherapeutic cycles with epirubicin in each cycle of 21 days. All patients underwent echocardiography for layer-specific STE analysis before and after all chemotherapy. Clinical data including cardiovascular risk factors were collected. According to the Framingham score, patients with cardiovascular risk factors were divided into groups with low, medium, and high risk. 134 patients existed in the final analysis. The accumulated dose of epirubicin for were 560.0 ± 103.8 mg. 97 (72.4%) patients had cardiovascular risk factors. According to the Framingham score, 57 (42.5%) patients categorized in high risk. Endocardial layer strain after chemotherapy were lower than those at baseline (p < 0.05, all), especially for patients with high risk. The changes of endocardial longitudinal strain during chemotherapy were associated with cardiovascular risks at baseline with correlation coefficient of 0.627. Our study found that layer-specific STE is valuable for early detection of toxicity-related myocardial injury for patients with breast cancer after epirubicin chemotherapy and cardiovascular risk factors have greatly influenced on cardiac function during chemotherapy. The endocardial layer strain is sensitive to evaluate early-stage toxicity-related myocardial injury after epirubicin chemotherapy.

Stable Low-Dose Oxygen Release Using H2O2/Perfluoropentane Phase-Change Nanoparticles with Low-Intensity Focused Ultrasound for Coronary Thrombolysis.

After the onset of myocardial infarction, extensive coronary thrombus and oxygen supply insufficiency lead to severe myocardial damage and heart failure. Recently, ultrasound-irradiated phase-change nanoparticles have been recognized for their cardiovascular thrombolysis potential. Therefore, we sought to establish a novel treatment method using hydrogen peroxide (H2O2)/perfluoropentane (PFP) phase-change nanoparticles with low-intensity focused ultrasound (LIFU) for the simulation of acute coronary thrombolysis and myocardial preservation. There were three groups in our study: Group A consisted of phosphate-buffered saline (PBS) as the blank control, group B consisted of SonoVue microbubbles and group C consisted of H2O2/PFP phase-change nanoparticles. The H2O2/PFP phase-change nanoparticles were prepared using a double-emulsification process. The in vitro experiments were conducted in an artificial circulatory system connected to an LIFU system and dissolved oxygen detector. Thrombolysis efficiency and oxygen release efficiency were compared among the groups. H2O2/PFP nanoparticles with 3% H2O2 (average size: 456.7 ± 31.2 nm, charge: -37.5 ± 5.22 mV) was the optimal selection in group C because of the stable loading capacity and stable low-dose oxygen release efficiency in the in vitro experiments. Thrombolytic weight loss and loss rates in group C (322.0 ± 40.8 mg, 54.8 ± 5.7%) were significantly higher than those in group A (36.2 ± 18.1 mg, 5.5 ± 2.5%) and group B (91.0 ± 11.9 mg, 14.3 ± 2.4%) (p < 0.01). The innovative method using H2O2/PFP phase-change nanoparticles with LIFU exhibited high thrombolytic efficiency and stable low-flow oxygen supply in the artificial circulatory system, providing a solid experimental foundation for the establishment of a novel treatment method for acute myocardial infarction.

Layer-Specific Strain for Long-Term Outcome Prediction After First-Onset Myocardial Infarction.

Many studies have reported the prognostic value of global strain obtained with speckle tracking echocardiography (STE) in patients with acute myocardial infarction (AMI). However, as a novel method derived from STE, layer-specific strain has seldom been evaluated with respect to prediction of AMI outcomes. We sought to investigate the predictive value of layer-specific strain and whether it has incremental value compared with conventional parameters, such as left ventricular ejection fraction and wall motion score index, and STE parameters. Our study was prospective. Ninety-two patients with first-onset AMI were enrolled and underwent echocardiography before coronary intervention for analysis of global and layer-specific strain. Cox proportional hazard ratio (HR) and receiver operating characteristic curve analyses were performed for the prediction of cardiac events and cardiac death. Fifty-three patients have had cardiac events during follow-up. Endocardial longitudinal strain has received relatively higher HRs for risk predictions of both cardiac events (HR = 1.69) and cardiac death (HR = 3.21) adjusted with clinical data. The areas under the receiver operating characteristic curves of the longitudinal strain at the endocardial layer from layer-specific strain were higher than those of global strain and conventional parameters for cardiac event prediction (p ˂ 0.05, all). Layer-specific strain is valuable for cardiac risk prediction after infarction and has incremental values in addition to conventional and global STE parameters. Myocardial damage at the endocardial layer was closely related to outcomes of AMI patients at long-term follow-ups.