Epithelial phenotype as a predictive marker for response to EGFR-TKIs in non-small cell lung cancer patients with wild-type EGFR.

Epithelial-to-mesenchymal transition (EMT) has profound impacts on cancer progression and also on drug resistance, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Nowadays, there is still no predictive biomarker identified for the use of EGFR-TKIs in non-small cell lung cancer (NSCLC) patients with wild-type EGFR. To clarify the role of EMT phenotype as a predictive marker for EGFR-TKI, we performed a retrospective study in 202 stage IV or recurrent NSCLC patients receiving gefitinib or erlotinib therapy from June 2008 to September 2012 in our institute. Clinical data and EGFR mutational status were collected, while epithelial, epithelial to mesenchymal, not specified or mesenchymal phenotype were classified according to EMT markers such as E-cadherin, fibronectin, N-cadherin and vimentin by immunohistochemistry. Epithelial phenotype was more frequently found in patients with EGFR mutation (p = 0.044). Epithelial phenotype was associated with a significantly higher objective response rate (23.5 vs. 11.1 vs. 0.0 vs. 2.4%, p = 0.011), longer progression-free survival (4.4 vs. 1.9 vs. 1.7 vs. 1.0 months, p < 0.001) and longer overall survival (11.5 vs. 8.9 vs. 4.5 vs. 4.9 months, p < 0.001) compared to epithelial to mesenchymal, not specified and mesenchymal phenotype in the wild-type EGFR subgroup. In the subgroup with EGFR mutation, the trend remained but without a statistically significant difference. In conclusion, epithelial phenotype was more likely expressed in patients with EGFR mutation and was associated with a better outcome in advanced NSCLC patients with wild-type EGFR, which indicates that the EMT phenotype might be a potential marker to guide EGFR-TKI therapy in this population.

Exploring the possible molecular targeting mechanism of Saussurea involucrata in the treatment of COVID-19 based on bioinformatics and network pharmacology.

OBJECTIVE: Based on bioinformatics and network pharmacology, the treatment of Saussurea involucrata (SAIN) on novel coronavirus (COVID-19) was evaluated by the GEO clinical sample gene difference analysis, compound-target molecular docking, and molecular dynamics simulation. role in the discovery of new targets for the prevention or treatment of COVID-19, to better serve the discovery and clinical application of new drugs. MATERIALS AND METHODS: Taking the Traditional Chinese Medicine System Pharmacology Database (TCMSP) as the starting point for the preliminary selection of compounds and targets, we used tools such as Cytoscape 3.8.0, TBtools 1.098, AutoDock vina, R 4.0.2, PyMol, and GROMACS to analyze the compounds of SAIN and targets were initially screened. To further screen the active ingredients and targets, we carried out genetic difference analysis (n = 72) through clinical samples of COVID-19 derived from GEO and carried out biological process (BP) analysis on these screened targets (P ≤ 0.05)., gene = 9), KEGG pathway analysis (FDR≤0.05, gene = 9), protein interaction network (PPI) analysis (gene = 9), and compounds-target-pathway network analysis (gene = 9), to obtain the target Point-regulated biological processes, disease pathways, and compounds-target-pathway relationships. Through the precise molecular docking between the compounds and the targets, we further screened SAIN's active ingredients (Affinity ≤ -7.2 kcal/mol) targets and visualized the data. After that, we performed molecular dynamics simulations and consulted a large number of related Validation of the results in the literature. RESULTS: Through the screening, analysis, and verification of the data, it was finally confirmed that there are five main active ingredients in SAIN, which are Quercitrin, Rutin, Caffeic acid, Jaceosidin, and Beta-sitosterol, and mainly act on five targets. These targets mainly regulate Tuberculosis, TNF signaling pathway, Alzheimer's disease, Pertussis, Toll-like receptor signaling pathway, Influenza A, Non-alcoholic fatty liver disease (NAFLD), Neuroactive ligand-receptor interaction, Complement and coagulation cascades, Fructose and mannose metabolism, and Metabolic pathways, play a role in preventing or treating COVID-19. Molecular dynamics simulation results show that the four active ingredients of SAIN, Quercitrin, Rutin, Caffeic acid, and Jaceosidin, act on the four target proteins of COVID-19, AKR1B1, C5AR1, GSK3B, and IL1B to form complexes that can be very stable in the human environment. Tertiary structure exists. CONCLUSION: Our study successfully explained the effective mechanism of SAIN in improving COVID-19, and at the same time predicted the potential targets of SAIN in the treatment of COVID-19, AKR1B1, IL1B, and GSK3B. It provides a new basis and provides great support for subsequent research on COVID-19.

Enhanced Broadband Plasmonic Absorbers with Tunable Light Management on Flexible Tapered Metasurface.

The growing attention in solar energy has motivated the development of highly efficient solar absorbers, and a metasurface absorber with broadband optical absorption is one of the main research interests. In this study, we developed an efficient metasurface absorber on a flexible film with a simple fabrication process. It consists of a polyimide nanocone substrate coated with gold and tungsten layers, exhibiting over 96% optical absorption in the visible range and a tunable absorption performance in the long wave range. From the analysis of experiment and simulation, the enhanced optical absorption is attributed to the synergistic effects of localized nanoparticle plasmon resonance and cavity plasmon resonance, and tunable light management comes from the strong infrared reflection of a gold layer and intrinsic absorption of variable tungsten layers. Meanwhile, the polarization-independent and omnidirectional optical absorption properties are demonstrated in the fabricated absorbers. Furthermore, this absorber shows the robustness against bending, maintaining the stable and excellent absorption performance after hundreds of bending tests. Our work offers a low-cost and straightforward tactic to design and fabricate flexible solar absorbers, and this metasurface absorber is a promising candidate for many exciting applications, such as emissivity control and flexible energy-related devices.

Lung cancer associated with cystic airspaces: CT and pathological features.

BACKGROUND: Lung cancer associated with cystic airspaces (LC-CAS) is a special type of lung cancer that is often misdiagnosed due to its similar imaging appearances to pulmonary bulla or pulmonary cyst. This study was designed to explore the imaging and pathological features of LC-CAS. METHODS: A retrospective analysis was performed on 35 LC-CAS patients treated in our center from January 2017 to January 2020. There were 23 men and 12 women aged 61.4±9.2 years, with a range of 44-78 years. All patients underwent chest computed tomography (CT), and the diagnoses were surgically and pathologically confirmed. RESULTS: The lesions were 0.5-3.0 cm (mean: 1.6±0.7 cm) in diameter. The CT signs of these lesions included lobulation sign (n=25), spicule sign (n=21), pleural indentation sign (n=22), vessel convergence sign (n=17), nodules on cystic wall (n=16), bronchial cut-off sign (n=15), uneven thickening of the cystic wall (n=10), and honeycombing (n=7). Postoperative pathological types included 30 cases of adenocarcinoma [which included 22 cases of invasive adenocarcinoma (IAC) and 8 cases of minimally invasive adenocarcinoma (MIA)], 4 cases of squamous cell carcinoma, and 1 case of adenosquamous carcinoma. CONCLUSIONS: LC-CAS has diverse CT signs. The most common pathological type of LC-CAS is adenocarcinoma.

High-temperature stable plasmonic and cavity resonances in metal nanoparticle-decorated silicon nanopillars for strong broadband absorption in photothermal applications.

Plasmonic metal nanoparticles in conjunction with the cavity mode resonance in crystalline silicon (c-Si) nanopillars (NPs) can help achieve strongly enhanced broadband light absorption far beyond the limit of bulk c-Si. However, a major concern arises from the stability of metal nanoparticles, particularly at a high temperature, as the diffusion and conglomeration of the nanoparticles will undermine the very basis for the advantageous plasmonic effect. We here carried out a systematic investigation of the thermal stability of different metal nanoparticles coated on 3D Si-based NPs and found that simple Al2O3 encapsulation could help stabilize the gold (Au) particles coated on Si NPs even when subjected to annealing at >1073 K while accomplishing excellent broadband optical absorption (∼95%) from 200 nm to 2500 nm. This could be assigned mainly to the excellent dispersion retention capability of the Al2O3-encapsulated Au nanoparticles and the beneficial plasmon resonance absorption among the Au nanoparticles and Si NPs, as also revealed from the FDTD simulation analysis. Finally, a rapid vapor generation application was demonstrated based on the optimized Au/Si NPs, where salt water drops could be directly injected onto the high-temperature photo-heated Au/Si NPs and could vaporize/bounce off quickly without leaving any salt precipitation on the surface. This new strategy can also pave the way for high-performance Si-based photothermal applications.

Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer.

OBJECTIVE: To investigate the effect of gemcitabine plus cisplatin chemotherapy on the percentage of CD4(+)CD25(+)FOXP3(+) and CD8(+)CD28(-) regulatory T cells (Tregs) in the peripheral blood of patients with nonsmall-cell lung cancer (NSCLC). METHODS: Peripheral blood was taken from patients with NCSLC (before and after chemotherapy) and control subjects with nonmalignant disease. The percentages of CD4(+)CD25(+)FOXP3(+) and CD8(+)CD28(-) Tregs were analysed using flow cytometry. RESULTS: Patients (n = 40) had significantly higher CD4(+)CD25(+)FOXP3(+) and CD8(+)CD28(-) percentages than control subjects (n = 24). CD4(+)CD25(+)FOXP3(+) and CD8(+)CD28(-) percentages increased with tumour progression, fell significantly after chemotherapy, but remained significantly higher than control values. CONCLUSIONS: CD4(+)CD25(+)FOXP3(+) and CD8(+)CD28(-) Treg percentages were higher in patients with NSCLC than control subjects, and increased in line with tumour progression. Percentages of CD4(+)CD25(+)FOXP3(+) and CD8(+)CD28(-) Tregs were significantly reduced following gemcitabine plus cisplatin chemotherapy.

Overcoming the blood-brain barrier for chemotherapy: limitations, challenges and rising problems.

Treatment of brain tumors with chemotherapy is limited mostly because of delivery impediments related to the blood-brain barrier (BBB). For gliomas, the most common and aggressive primary brain tumor, treatment includes surgery, radiotherapy, and chemotherapy usually administered orally or intravenously. These routes do not deliver effective concentrations. To complicate matters, chemotherapy is usually a long treatment. Therefore, transient disruption of the BBB is likely insufficient to deliver effective intratumoral concentrations of anticancer drugs. This review briefly updates current strategies for overcoming the BBB with emphasis on their limitations and challenges intrinsic to the biology of cancer cells.

Changes of CD4+CD25+FOXP3+ and CD8+CD28- regulatory T cells in non-small cell lung cancer patients undergoing surgery.

Little is known about the regulatory T cells (Tregs) in the peripheral blood after surgery of non-small cell lung cancer (NSCLC) patients. In this study, we investigated whether CD4+CD25+FOXP3+ and CD8+CD28- regulatory T cells are decreased in the peripheral blood of NSCLC patients undergoing surgery. The study group (n = 49) comprised NSCLC, and the control group (n = 24) consisted of age- and sex-matched nonmalignant diseases. The prevalence of CD4+CD25+FOXP3+ and CD8+CD28- Tregs was analyzed using flow cytometry. The study group showed significantly higher percentage of CD4+CD25+FOXP3+ and CD8+CD28- Tregs than control. The percentage of CD4+CD25+FOXP3+ and CD8+CD28- Tregs increased with tumor stage. One way ANOVA test shows the significant differences between all subgroups. LSD test shows that there was a statistical significance between each of the two subgroups except stage II in CD4+CD25+FOXP3+ Tregs and control vs. each stage, stage I vs. stage III, and stage IV in CD8+CD28- Tregs. There is no significant difference among stages II, III, and IV in CD8+CD28- Tregs. No differences were found between squamous carcinoma and adenocarcinoma. These levels were dropped significantly after operation. Furthermore postoperative Treg percentage in the early stages (stage I and stage II) was not statistically different from that of controls. Postoperative Treg percentage in advanced stage (III+IV) remained above the values shown by controls. Our findings indicate that the percentage of CD4+CD25+FOXP3+ and CD8+CD28- Tregs correlated with the pathological stage in NSCLC and tumor burden.

Natural products targeting autophagy via the PI3K/Akt/mTOR pathway as anticancer agents.

The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a key regulator of authophagy. Natural products show anticancer activity and often induce apoptosis or autophagy. The crosstalk between these two types of cell death makes autophagy an interesting target since drugs targeting this process not only can induce cell death by inducing autophagy but can also sensitize cells to apoptosis. Autophagy is also a protective mechanism associated with increased resistance to chemotherapy. In this review, we discuss natural products known to induce autophagy cell death in cancer cells via the PI3K/Akt/mTOR pathway.