Atorvastatin Calcium Inhibits PDGF-ββ-Induced Proliferation and Migration of VSMCs Through the G0/G1 Cell Cycle Arrest and Suppression of Activated PDGFRβ-PI3K-Akt Signaling Cascade

Background/Aims: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular lesions, such as atherosclerosis and restenosis. PDGF-ββ, an isoform of PDGF (platelet-derived growth factor), has been demonstrated to induce proliferation and migration of VSMCs. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has favorable protective effects on VSMCs. This study examined the effects of atorvastatin calcium on the proliferation and migration of PDGF-ββ-treated VSMCs, as well as its underlying mechanisms. Methods: MTT assays, Edu imaging, cell cycle analysis, wound healing assays, transwell migration assays, and western blot analysis were performed. Results: Atorvastatin calcium significantly inhibited cell proliferation, DNA synthesis and cell migration of PDGF-ββ-treated VSMCs. We demonstrated that atorvastatin calcium induced cell cycle arrest in the G0/G1 phase in response to PDGF-ββ stimulation and decreased the expression of G0/G1-specific regulatory proteins, including proliferating cell nuclear antigen (PCNA), CDK2, cyclin D1, cyclin E and CDK4 in PDGF-ββ-treated VSMCs. Moreover, pretreatment with atorvastatin calcium inhibited the PDGF-ββ-treated phosphorylation of PDGFRβ and Akt, whereas atorvastatin calcium did not affect the phosphorylation of PLC-γ1 or (ERK) 1/2. Conclusion: Our data suggested that atorvastatin calcium inhibited abnormal proliferation and migration of VSMCs through G0/G1 cell cycle arrest and suppression of the PDGFRβ-Akt signaling cascade

Quality of life between home-based and outpatient pulmonary rehabilitation in patients after surgical resection for lung cancer: protocol for a prospective, single-blind, randomised controlled trial

Introduction Lung cancer remains a highly fatal disease. Surgical resection has been proven to be the most effective treatment for early-stage lung cancer. The conventional hospital-based pulmonary rehabilitation (PR) is shown to reduce symptoms, improve exercise capacity and impact the quality of life (QoL) for lung cancer patients. To date, scientific evidence on the effectiveness of home-based PR for patients with lung cancer following surgery is scarce. We aim to explore if home-based PR is non-inferior to outpatient PR for patients with lung cancer following surgical resection.Methods and analysis This study is a two-arm, parallel-group, assessor-blind, single-centre, randomised controlled trial. Participants will be recruited from West China Hospital, Sichuan University and randomly allocated to either an outpatient group or a home-based group at a ratio of 1:1. The PR programme involves self-management and exercises. The exercise includes warm-up (10 min), aerobic training (20 min), resistance training (15 min) and cool-down (10 min), lasting 4 weeks, with two sessions per week either at home or in the outpatient setting. The intensity will be adjusted according to the modified Borg rating of perceived exertion and heart rate before and after each exercise session. The primary outcome is QoL measured by EORTC QLQ-C30 & LC 13 after an intervention. Secondary outcomes include physical fitness measured by a 6 min walk test and stair-climbing test and symptom severity measured by patient-reported questionnaires and pulmonary function. The main hypothesis is that home-based PR is non-inferior to outpatient PR for patients with lung cancer following surgical resection.Ethics and dissemination The trial has been approved by the Ethical Committee of West China Hospital and is also registered with the Chinese Clinical Trial Registry. The results of this study will be disseminated through peer-reviewed publications and presentations at national and international conferences.Trial registration number ChiCTR2100053714

PDTAC: Targeted photodegradation of GPX4 triggers Ferroptosis and potent antitumor immunity

Targeted degradation of proteins, especially those regarded as ‘undruggable’, attracts wide attention to develop novel potential therapeutic strategy. GPX4, a key enzyme regulating ferroptosis, is such a target whose inhibition is currently limited to molecules acting through covalently binding. Here, we have developed a targeted photolysis approach to achieve the efficiently degradation of GPX4. The Photo-Degradation TArgeting Chimeras (PDTACs) were synthesized by conjugating a clinically approved photosensitizer Verteporfin to GPX4-targeting peptides. Although the ligands themselves exhibit neither inhibitory nor degrading activity towards GPX4, these chimeras degraded selectively the target protein in living cells upon red-light irradiation. In contrast to the application of Verteporfin alone, the targeted photolysis of GPX4 resulted in dominant ferroptotic cell death in malignant cancer cells of different origins. Moreover, the dying cells resulted from our chimeras exhibited potent immunogenicity in vitro, and elicited more efficiently anti-tumor immunity in vivo in comparison with those dying from Verteporfin. Our approach therefore provides a novel method to dysfunction GPX4 based on noncovalent binding and specifically trigger immunogenic ferroptosis, which may boost the development of triggering ferroptosis as a potential strategy in cancer immunotherapy

Prognostic value of consolidation-to-tumor ratio on computed tomography in NSCLC: a meta-analysis

Abstract Background Although several studies have confirmed the prognostic value of the consolidation to tumor ratio (CTR) in non-small cell lung cancer (NSCLC), there still remains controversial about it. Methods We systematically searched the PubMed, Embase, and Web of Science databases from inception to April, 2022 for eligible studies that reported the correlation between CTR and prognosis in NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and pooled to assess the overall effects. Heterogeneity was estimated by I 2 statistics. Subgroup analysis based on the cut-off value of CTR, country, source of HR and histology type was conducted to detect the sources of heterogeneity. Statistical analyses were performed using STATA version 12.0. Results A total of 29 studies published between 2001 and 2022 with 10,347 patients were enrolled. The pooled results demonstrated that elevated CTR was associated with poorer overall survival (HR = 1.88, 95% CI 1.42–2.50, P < 0.01) and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS) (HR = 1.42, 95% CI 1.27–1.59, P < 0.01) in NSCLC. According to subgroup analysis by the cut-off value of CTR and histology type, both lung adenocarcinoma and NSCLC patients who had a higher CTR showed worse survival. Subgroup analysis stratified by country revealed that CTR was a prognostic factor for OS and DFS/RFS/PFS in Chinese, Japanese, and Turkish patients. Conclusions In NSCLC patients with high CTR, the prognosis was worse than that with low CTR, indicating that CTR may be a prognostic factor

Potential epidemiological impact of the 2017 American College of Cardiology/American Heart Association high blood pressure guideline on the Chinese population: a cross-sectional study in rural areas of Liaoning Province

Objectives The present study estimated the percentage of rural Chinese adults with hypertension and recommended pharmacological antihypertensive treatment according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline compared with the 2010 Chinese Guideline for the Management of Hypertension.Design Cross-sectional study.Setting Three counties in rural areas of northeastern China.Participants A total of 11 747 eligible individuals aged ≥35 years from rural areas of northeastern China were selected for the present analysis.Main outcome measures The percentage of rural Chinese adults with hypertension and recommended pharmacological antihypertensive treatment according to the 2017 ACC/AHA guideline and the 2010 Chinese Guideline for the Management of Hypertension, and the proportion of rural Chinese adults taking antihypertensive medication with blood pressure (BP) above the 2017 ACC/AHA guideline and the 2010 Chinese guideline treatment goal.Results The mean age of the study population was 53.9±10.8 years and 53.7% of the participants were women. According to the 2017 ACC/AHA guideline and the 2010 Chinese guideline, the crude prevalence of hypertension was 72.2% and 49.8%, respectively, and the percentage of recommended antihypertensive medications for rural Chinese adults was 56.4% and 51.4%, respectively. Among these rural Chinese adults taking antihypertensive medications, 96.7% had above goal BP according to the 2017 ACC/AHA guideline compared with 86.1% with above goal BP according to the 2010 Chinese guideline.Conclusion The present analysis demonstrated that compared with the 2010 Chinese guideline, the 2017 ACC/AHA hypertension guideline will result in a substantial increase in the percentage of rural Chinese adults defined as having hypertension and a small increase in the percentage of adults who are recommended antihypertensive medications. More intensive management is suggested to improve the control rate of hypertension among rural Chinese adults