Tumor microenvironment-initiated lipid redox cycling for efficient triple-negative breast cancer therapy.

The use of overwhelming reactive oxygen species (ROS) attack has shown great potential for treating aggressive malignancies; however, targeting this process for further applications is greatly hindered by inefficiency and low selectivity. Here, a novel strategy for ROS explosion induced by tumor microenvironment-initiated lipid redox cycling was proposed, which was developed by using soybean phosphatidylcholine (SPC) to encapsulate lactate oxidase (LOX) and sorafenib (SRF) self-assembled nanoparticles (NPs), named LOX/SRF@Lip. SPC is not only the delivery carrier but an unsaturated lipid supplement for ROS explosion. And LOX catalyzes excessive intratumoral lactate to promote the accumulation of large amounts of H2O2. Then, H2O2 reacts with excessive endogenous iron ions to generate amounts of hydroxyl radical for the initiation of SPC peroxidation. Once started, the reaction will proceed via propagation to form new lipid peroxides (LPO), resulting to devastating LPO explosion and widespread oxidative damage in tumor cells. Furthermore, SRF makes contribution to mass LPO accumulation by inhibiting LPO elimination. Compared to normal tissue, tumor tissue has higher levels of lactate and iron ions. Therefore, LOX/SRF@Lip shows low toxicity in normal tissues, but generates efficient inhibition on tumor proliferation and metastasis, enabling excellent and safe tumor-specific therapy. This work offers new ideas on how to magnify anticancer effect of ROS through rational nanosystem design and tumor-specific microenvironment utilization.

Effects of Selenium Auricularia cornea Culture Supplementation on Growth Performance, Antioxidant Status, Tissue Selenium Concentration and Meat Quality in Growing-Finishing Pigs.

Selenium Auricularia cornea culture (SAC) is a new source of organic selenium. Two experiments were conducted to determine the available energy of SAC fed to pigs and to evaluate the effects of dietary SAC supplementation on growth performance, serum biochemical profiles, fecal short chain fatty acids (SCFA), meat quality, tissue selenium concentration, and oxidative stability of fresh meat in growing-finishing pigs. In Experiment (Exp.) 1, 12 barrows with average body weight (BW) of 42.40 ± 5.30 kg were randomly allotted to two groups and fed the basal diet and SAC-supplemented diet, individually. In Exp. 2, 96 growing-finishing pigs (BW: 91.96 ± 7.55 kg) were grouped into four dietary treatments; each treatment contained six replicates with four pigs per replicate. The four treatments fed a control diet and three experimental diets supplemented with 0.6%, 1.2%, and 2.4% SAC, respectively. The trial lasted for 45 days. The results revealed that digestible energy (DE) of SAC was 11.21 MJ/kg. The average daily gain (ADG) was improved in pigs fed 1.2% and 2.4% SAC during day 24 to 45 and the overall period. Dietary 1.2% and 2.4% SAC supplementation had a lower F/G (p < 0.05) than the control diet during different stages. Dietary SAC supplementation increased fecal butyrate contents (p < 0.05), and pigs fed 1.2% and 2.4% SAC diets had a higher MCT1 mRNA expression (p = 0.04) in the colon. Pigs fed 2.4% SAC had higher GSH-Px contents (p < 0.05) in serum, liver, and longissimus dorsi muscle (LDM) than those in the control group. The 2.4% SAC-supplemented group revealed a higher Se content (p < 0.05) in LDM and a lower MDA concentration (p < 0.05) in fresh meat during the simulated retail display on day six. In conclusion, this study suggested that SAC was more effective in improving growth, enhancing the antioxidant status, depositing Se in muscle, and increasing meat oxidative stability of pigs.

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020.

BACKGROUND: In recent years, new drug development on lung cancer is in full swing in China. The aim of this study was to overview the changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020. METHODS: We analysed anti-lung cancer drug clinical trials registered on three websites including the China National Medical Products Administration Centre for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov. FINDINGS: A total of 1595 anti-lung cancer drug clinical trials from Jan 1st, 2005 to Dec 31st, 2020 were extracted, which included 630 (39•5%) investigator-initiated trials (IITs), 698 (43•8%) domestic industry-sponsored trials (ISTs), and 267 (16•7%) international ISTs. During the past 16 years, the number of anti-lung cancer clinical trials including IITs and domestic ISTs had a remarkable growth, however, the number of international ISTs increased slowly. The number of principal clinical trial units also increased significantly over time. Of the 1595 trials, the largest growth was observed in phase I trials during 2013-2020, with an average annual growth rate of 38•6%. 278 trials were led by principal investigators (PI) from Guangdong, followed by Beijing (n=273) and Shanghai (n=257). Among the 965 ISTs, clinical trials involving targeted drugs (588, 60•9%) accounted for the largest proportion, followed by immunotherapeutic drugs (284, 29•4%), cytotoxic drugs (75, 7•8%), and traditional Chinese medicine (18, 1•9%). In terms of targeted drugs, EGFR-TKIs remained the most studied drugs (225/588, 38•27%). As for immunotherapy, 125 out of 284 (44•01%) trials involved PD-1 inhibitors, 60 (21•13%) trials involved PD-L1 inhibitors, and seven (2•46%) trials involved CTLA-4 inhibitors. INTERPRETATION: In the past 16 years, the development of anti-lung cancer drug clinical trials has achieved much progress in mainland China. The most progress lied in targeted therapy and immunotherapy. FUNDING: This work was financially supported in part by China National Major Project for New Drug Innovation (2017ZX09304015) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001).

Cigarette Constituent Health Communications for Smokers: Impact of Chemical, Imagery, and Source.

INTRODUCTION: Communication campaigns are incorporating tobacco constituent messaging to reach smokers, yet there is a dearth of research on how such messages should be constructed or will be received by smokers. METHODS: In a 2 × 2 × 2 experiment, we manipulated three cigarette constituent message components: (1) the toxic constituent of tobacco (arsenic vs. lead) with a corresponding health effect, (2) the presence or absence of an evocative image, and (3) the source of the message (FDA vs. no source). We recruited smokers (N = 1669, 55.4% women) via an online platform and randomized them to one of the eight message conditions. Participants viewed the message and rated its believability and perceived effectiveness, the credibility of the message source, and action expectancies (ie, likelihood of seeking additional information and help with quitting as a result of seeing the message). RESULTS: We found significant main effects of image, constituent, and source on outcomes. The use of arsenic as the constituent, the presence of an evocative image, and the FDA as the source increased the believability, source credibility, and perceived effectiveness of the tobacco constituent health message. CONCLUSIONS: Multiple elements of a constituent message, including type of constituent, imagery, and message source, impact their reception among smokers. Specifically, communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes that are associated with subsequent attitude and behavioral changes. IMPLICATIONS: This article describes how components of communication campaigns about cigarette constituents are perceived. Multiple elements of a tobacco constituent message, including type of constituent, image, and message source may influence the reception of messages among current smokers. Communication campaigns targeting smokers that utilize arsenic as the tobacco constituent, visual imagery, and the FDA logo may be particularly effective in changing key outcomes among smokers. The effects of such campaigns should be examined, as well as the mechanisms through which such campaigns affect change.

Does film smoking promote youth smoking in middle-income countries?: A longitudinal study among Mexican adolescents.

OBJECTIVE: To determine whether exposure to smoking imagery in films predicts smoking onset among never-smoking Mexican adolescents. METHODS: The analytic sample was comprised of 11- to 14-year-old secondary school students who reported never having tried smoking at baseline, 83% (1,741/2,093) of whom were successfully followed-up after 1 year. Exposure to 42 popular films that contained smoking was assessed at baseline, whereas smoking behavior and risk factors were assessed at baseline and at follow-up. Logistic regression was used to estimate bivariate and adjusted relative risks (ARR) of trying smoking and current smoking at follow-up. RESULTS: At follow-up, 36% reported having tried smoking and 8% reported having smoked in the previous month. Students who were successfully followed-up were exposed to an average of 43.8 minutes of smoking in the films they reported viewing at baseline. ARRs indicated that students in the two highest levels of exposure to film smoking were more than twice as likely to have smoked in the previous 30 days at follow-up [ARR(3v1) = 2.44; 95% confidence interval (CI), 1.31-4.55; ARR(4v1) = 2.23; 95% CI, 1.19-4.17]. The ARR of having tried smoking by the time of follow-up reached statistical significance only when comparing the third highest to the lowest exposure group (ARR(3v1) = 1.54; 95% CI, 1.01-2.64). Having a parent or best friend who smoked at baseline were the only other variables that independently predicted both outcomes. CONCLUSIONS: Exposure to movie smoking is a risk factor for smoking onset among Mexican youth, although this risk appears weaker than in countries with stronger tobacco marketing regulations.