Background It has been widely reported that curcumin (CUR) exhibits anticancer activity and triggers the apoptosis of human A549 non-small-cell lung cancer (NSCLC) cells. However, its application is limited owing to its poor solubility and bioavailability. Therefore, there is an urgent need to develop a new CUR formulation with higher water solubility and better biocompatibility for clinical application in the future. Materials and methods In this study, CUR-loaded methoxy polyethylene glycol–polylactide (CUR/mPEG–PLA) polymeric micelles were prepared by a thin-film hydration method. Their characteristics and antitumor effects were evaluated subsequently. Results The average size of CUR/mPEG–PLA micelles was 34.9±2.1 nm with its polydispersity index (PDI) in the range of 0.067–0.168. The encapsulation efficiency and drug loading were 90.2%±0.78% and 9.1%±0.07%, respectively. CUR was constantly released from the CUR/mPEG–PLA micelles, and its cellular uptake in A549 cells was significantly increased. It was also found that CUR/mPEG–PLA micelles inhibited A549 cell proliferation, increased the cell cytotoxicity, induced G2/M stage arrest and promoted cell apoptosis. Moreover, the CUR/mPEG–PLA micelles suppressed the migration and invasion of A549 cells more obviously than free CUR. Additionally, CUR/mPEG–PLA micelles inhibited human umbilical vein endothelial cells migration, invasion and corresponding tube formation, implying the antiangiogenesis ability. Its enhanced antitumor mechanism may be related to the reduced expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, MMP-9 and Bcl-2 as well as the increased expression of Bax. Conclusion The mPEG–PLA copolymer micelles can serve as an efficient carrier for CUR. The CUR/mPEG–PLA micelles have promising clinical potential in treating NSCLC.

Background Interstitial lung disease (ILD) is associated with substantial morbidity and mortality, which is one of the key systematic manifestations of connective tissue disease (CTD). Tripterygium wilfordii, known as Leigongteng in Chinese, has been applied to treat connective tissue disease-related interstitial lung disease (CTD-ILD) for many years. Triptolide is a key effective component from Tripterygium wilfordii. But the molecular mechanism of Triptolide for treating CTD-ILD is not yet clear. Methods Gaining insight into the molecular mechanism of Triptolide intervention CTD-ILD, we used the method of network pharmacology. And then we conducted drug-target networks to analyse the potential protein targets between Triptolide and CTD-ILD. Finally, AutoDock Vina was selected for molecular docking. Results By analysing the interaction genes between Triptolide and CTD-ILD, 242 genes were obtained. The top 10 targets of the highest enrichment scores were STAT3, AKT1, MAPK1, IL6, TP53, MAPK3, RELA, TNF, JUN, JAK2. GO and KEGG enrichment analysis exhibited that multiple signalling pathways were involved. PI3K-Akt, multiple virus infections, cancer signalling, chemokine, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. And it is related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. Molecular docking shows Triptolide can bind with its target protein in a good bond by intermolecular force. Conclusions This study preliminarily reveals the internal molecular mechanism of Triptolide interfere with CTD-ILD through multiple targets, multiple access, validated through molecular docking. KEY MESSAGES Triptolide intervention CTD-ILD, which are related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. PI3K-Akt, multiple virus infections, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. Triptolide can bind with related target protein in a good bond by Intermolecular force, exhibiting a good docking activity.

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FUS1 is one of the most important tumor suppressor genes in lung cancer, as well as an important immunomodulatory molecule. Interleukin (IL)-12 has attracted considerable interest as a potential anti-tumor cytokine. Cationic liposome has been shown to effectively deliver therapeutic genes to the lungs and control metastatic lung tumors when administered intravenously. Here we evaluated the enhanced efficacy of cationic liposome-mediated delivery of FUS1 and human IL (hIL)-12 eukaryotic coexpression plasmid (pVITRO2-FUS1-hIL-12) against the human lung cancer in HuPBL-NOD/SCID mice model by local and systemic administration, and explored the related molecular mechanism. Our study demonstrated that FUS1-hIL-12 coexpression could more sufficiently inhibit tumor growth and experimental lung metastasis, significantly prolong the survival of experimental lung metastasis mice. Moreover, FUS1-hIL-12 coexpression performed higher antitumor activity and lower toxicity in the inhibition of experimental lung metastatic tumor compared to cisplatin. We further identified that FUS1-hIL-12 coexpression could induce strong antitumor immune response by secreting much higher levels of human interferon-γ (hIFN-γ) and hIL-15, enhancing expression of MHC-I and Fas, increasing infiltration of activated human CD4+ and CD8+ T lymphocytes. FUS1-hIL-12 coexpression could also obviously induce tumor cell apoptosis and inhibit tumor cell proliferation partly by higher activation of STAT1 signal pathway and upregulation of p53. In addition, FUS1-hIL-12 coexpression also superiorly reduced the angiogenesis in tumors, which might be associated with downregulation of VEGF and VEGFR, and upregulation of human IP-10. Our results therefore suggest that cationic liposome-mediated FUS1-hIL-12 coexpression may be a new promising strategy for lung cancer treatment in clinical studies.

Background: Tripterygium wilfordii Hook. F (TwHF), a Chinese herbal medicine used to treat CTD-ILD patients in China, has been previously found to have immunoinhibitory, antifibrotic and anti inflammatory effects. It has also shown good results in treating autoimmune and inflammatory diseases.Objectives: This systematic review and meta-analysis aims to evaluate the efficacy and safety of TwHF for CTD-ILD.Methods: A systematic search was performed on PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, Scopus, CNKI, Wanfang, VIP, and CBM databases up to May 2021. Randomized controlled trials (RCTs) comparing TwHF plus conventional therapy versus conventional therapy alone were included. We followed the PRISMA checklist, and applied Cochrane handbook 5.1.0 and RevMan 5.3 for data analysis and quality evaluation of the included studies.Results: Based on Cochrane handbook 5.1.0, nine RCTs consisting 650 patients met the inclusion/exclusion criteria and were selected for further analysis. The obtained data showed significant improvement in lung function with TwHF plus conventional treatment compared with conventional treatment (post-treatment FVC% (MD= 8.68, 95%Cl (5.10, 12.26), p < 0.00001), FEV1% (MD = 11.24, 95%Cl (6.87, 15.61), p < 0.00001), TLC% (MD = 5.28, 95%Cl (0.69, 9.87), p = 0.02)], but no significant difference in the post-treatment DLCO% [(MD = 4.40, 95%Cl (−2.29, 11.09), p = 0.20)]. Moreover, the data showed that TwHF combined with conventional treatment significantly reduced the HRCT integral of patients [MD = -0.65, 95% (-1.01, -0.30), p = 0.0003], the level of erythrocyte sedimentation rate (MD = −9.52, 95%Cl (−11.55, −7.49), p < 0.00001), c-reactive protein (CRP) (MD = −8.42, 95%Cl (−12.47, −4.38), p < 0.0001), and rheumatoid factor (MD = −25.48, 95%Cl (−29.36, −21.60), p < 0.00001). Compared to conventional therapy, TwHF combined with conventional therapy significantly improved clinical effects (RR = 1.33, 95%Cl (1.17, 1.51), p < 0.0001), in five trials with 354 patients. In terms of improvement of symptoms and signs, the TwHF group showed a more significant improvement than the conventional treatment group (Cough (MD = −0.96, 95%Cl (−1.43, −0.50), p < 0.0001), velcro rales (MD = −0.32, 95%Cl (−0.44, −0.20), p < 0.00001), shortness of breath (MD = −1.11, 95%Cl (−1.67, −0.56), p < 0.0001)], but no statistical difference in dyspnea (MD = −0.66, 95%Cl (−1.35, 0.03), p = 0.06). There was no statistical significance in the incidence of adverse reactions.Conclusion: The performed meta-analysis indicated that TwHF combined with conventional treatment was more beneficial to patients for improving symptoms, lung function and laboratory indicators. As it included studies with relatively small sample size, the findings require confirmation by further rigorously well-designed RCTs.