STS â ¡A inhibited angiogenesis of lung adenocarcinoma by activating FOXO3 to inhibit CXCL1/STAT3/VEGF pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Sulfotanshinone IIA sodium (STS IIA) has been proven to have an anticancer effect. However, its role in LUAD and its underlying mechanism remain unclear. OBJECTIVE: To investigate the role and mechanism of STS IIA in LUAD angiogenesis. METHODS: The mRNA levels of genes, including forkhead box O3 (FOXO3) and chemokine C-X-C motif ligand 1 (CXCL1), were detected by qRT-PCR. The levels of proteins, including FOXO3, CXCL1, and vascular endothelial growth factor (VEGF), were measured by Western blot. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by the EdU assay and the tubule formation assay, respectively. The binding relationship between FOXO3 and CXCL1 was detected by dual-luciferase reporter assay. RESULTS: Our results illustrated that different concentrations of STS IIA inhibited the proliferation and angiogenesis of HUVECs. FOXO3 regulated the proliferation and angiogenesis of HUVECs inhibited by STS ⅡA via targeting CXCL1. Subsequently, we proved that exogenous CXCL1 alleviated the inhibition of proliferation and angiogenesis of HUVECs regulated by STS IIA via activating the STAT3/VEGF pathway. Finally, we found that STS IIA inhibited the angiogenesis of lung adenocarcinoma though FOXO3 to inhibit the CXCL1/STAT3/VEGF pathway. CONCLUSION: Our study finally elucidated the underlying molecular mechanism by which STS ⅡA inhibits LUAD angiogenesis.

Immune checkpoint inhibitor-related chronic pneumonitis: a case report and literature review.

Immune checkpoint inhibitor (ICI)-related chronic pneumonitis is rare. Limited information is available on the characteristics of this condition. Herein, we present the case of a 54-year-old man with recurrent severe ICI-related pneumonitis. The patient developed fever and dyspnea during both episodes of pneumonitis. He had been previously diagnosed with gastric signet ring cell carcinoma and was undergoing treatment with an anti-PD-1 combination chemotherapy regimen. We reviewed previous case reports of ICI-related pneumonitis according to the primary cancer, time of onset in relation to ICI therapy and chest imaging findings. ICI-related pneumonitis can progress to chronic pneumonitis. Repeated computed tomography imaging showing lung changes in the same location may help to make the diagnosis.

Immune checkpoint inhibitors (ICIs) are a type of medicine that helps fight stomach cancer but sometimes they can cause problems with the lungs. This case report is about a man who had two bad lung incidents after taking ICI medicine. He had trouble breathing and fever both times. Other people have had similar problems with their lungs after being given ICI treatment. We compared chest pictures of the patient receiving ICI treatment over time and saw changes in the same spot meaning there might be a long-term problem with the lungs. We need to do more research to figure out how to treat this problem better.

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.

CONTEXT: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. OBJECTIVE: Our study explores the effect and mechanism of STS against LUAD. MATERIALS AND METHODS: LUAD cells were treated with 100 µM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. RESULTS: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. DISCUSSION AND CONCLUSIONS: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

Analysis of Antibiotic Use Patterns and Trends Based on Procurement Data of Healthcare Institutions in Shaanxi Province, Western China, 2015-2018.

Overuse of antibiotics has caused a series of global problems, especially in the underdeveloped western regions where healthcare systems are fragile. We used antibiotic procurement data of all healthcare institutions to analyze the total amount, patterns and trends of antibiotic use in Shaanxi Province, western China between 2015 and 2018. Antibiotic utilization was quantified using the standard Anatomical Therapeutic Chemical (ATC)/Defined daily dose (DDD) methodology. The World Health Organization's "Access, Watch and Reserve" (AWaRe) classification and European Surveillance of Antimicrobial Consumption (ESAC) drug-specific quality indicators were also adopted to evaluate the appropriateness and quality of antibiotic utilization. Overall, antibiotic consumption decreased from 11.20 DID in 2015 to 10.13 DID (DDDs per 1000 inhabitants per day) in 2016, then increased to 12.99 DID in 2018. The top three antibiotic categories consumed in 2018 were J01C (penicillins) 33.58%, J01D (cephalosporins) 29.76%, and J01F (macrolides) 19.14%. Parenteral antibiotics accounted for 27.41% of the total consumption. The largest proportion of antibiotic use was observed in primary healthcare institutions in rural areas, which accounts for 51.67% of total use. Consumption of the Access group, the Watch group, the Reserve group of antibiotics was 40.31%, 42.28% and 0.11%, respectively. Concurrently, the consumption of J01D and the percentage of J01 (DD + DE) (third and fourth generation cephalosporins) were at a poor level according to the evaluation of ESAC quality indicators. The total antibiotic consumption in Shaanxi Province had been on an upward trend, and the patterns of antibiotic use were not justified enough to conclude that it was rational. This is partly because there was high preference for the third and fourth generation cephalosporins and for the Watch group antibiotics.

The Effects of a New Public Medicine Procurement Policy on Medicine Price in Shaanxi Province, Western China: An Interrupted Time Series Analysis.

Objectives: To assess the effects on medicine price, a new public medicine procurement policy (NPMPP) undertaken in western China in 2015. Methods: An interrupted time series analysis was used to evaluate the impact of NPMPP on the prices of emergency medicines, gynaecological medicines, and paediatric medicines in Shaanxi Province, western China. Based on the procurement records in all the public health institutions in Shaanxi Province, we built three regression models. The monthly average price growth rate of the three categories of medicines was analysed covering the period 2015 to 2017. Findings: Before the intervention, there was an increasing trend in the monthly average growth rate of the three categories of medicines, but significant only in emergency medicines and paediatric medicines. After the introduction of NPMPP, the increasing trend was accelerated for both the emergency medicines (coefficient = 0.114, P < 0.001) and gynaecological medicines (coefficient = 0.078, P < 0.05), whereas the increasing trend for paediatric medicines was slowed down after the intervention (coefficient = -0.024, P < 0.05). Conclusion: Using interrupted time series analysis, we identified a statistically significant increase in the price growth rate of emergency medicines and gynaecological medicines, but a statistically significant decrease in the price growth rate of paediatrics, following the introduction of NPMPP. The impact of NPMPP on emergency medicines was greater than that on gynaecological medicines. To inhibit the growth trend of drug price, effective policies need to be introduced.

Knockdown of high mobility group box 3 impairs cell viability and colony formation but increases apoptosis in A549 human non-small cell lung cancer cells.

Previous research has linked high mobility group box 3 (HMGB3) overexpression to the malignant progression and poor prognosis of non-small cell lung cancer (NSCLC). The present study investigated the role of HMGB3 in cell survival and colony formation of NSCLC cells. Stable knockdown of HMGB3 in A549 cells was achieved by lentiviral-based shRNA interference and verified by detection of the transcriptional and translational level of HMGB3 with reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The influence of HMGB3 knockdown on A549 cell viability and apoptotic rate was evaluated by Cell Counting Kit-8 assay and flow cytometry following annexin V staining, respectively. The proliferative capacity of A549 cells with or without HMGB3 knockdown was compared by measuring their colony forming efficiency. The results of the current study revealed that HMGB3 knockdown significantly reduced cell viability and colony forming efficiency while promoting apoptosis in A549 cells, indicating that HMGB3 may be pivotal for the survival and colony formation of A549 cells, serving a notable role in NSCLC progression.