Identification of crucial anoikis-related genes as novel biomarkers and potential therapeutic targets for lung adenocarcinoma via bioinformatic analysis and experimental verification.

Lung adenocarcinoma (LUAD) is a malignant tumor of the respiratory system that has a poor 5-year survival rate. Anoikis, a type of programmed cell death, contributes to tumor development and metastasis. The aim of this study was to develop an anoikis-based stratified model, and a multivariable-based nomogram for guiding clinical therapy for LUAD. Through differentially expressed analysis, univariate Cox, LASSO Cox regression, and random forest algorithm analysis, we established a 4 anoikis-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of LUAD patients in the TCGA and GEO databases, respectively. The low and high-risk score LUAD patients stratified by the model showed different tumor mutation burden, tumor microenvironment, gemcitabine sensitivity and immune checkpoint expressions. Through immunohistochemical analysis of clinical LUAD samples, we found that the 4 anoikis-related genes (PLK1, SLC2A1, ANGPTL4, CDKN3) were highly expressed in the tumor samples from clinical LUAD patients, and knockdown of these genes in LUAD cells by transfection with small interfering RNAs significantly inhibited LUAD cell proliferation and migration, and promoted anoikis. In conclusion, we developed an anoikis-based stratified model and a multivariable-based nomogram of LUAD, which could predict the survival of LUAD patients and guide clinical treatment.

Magnetically controlled nanorobots induced oriented and rapid clearance of the cytokine storm for acute lung injury therapy.

Cytokine storms characterized by excessive secretion of circulating cytokines and immune-cell hyperactivation are life-threatening systemic inflammatory syndromes. The new strategy is in great demand to inhibit the cytokine storm. Here, we designed a type of magnetically controlled nanorobots (MAGICIAN) by fusing neutrophil membranes onto Fe3O4 nanoparticles (Fe3O4NPs). In our study, the receptors of neutrophil membranes were successfully coated to the surface of Fe3O4NPs. The associated membrane functions of neutrophils were highly preserved. MAGICIAN could in vitro neutralize the inflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Interestingly, MAGICIAN could be navigated to the liver sites under magnetic control and accelerated the cytokine clearance by the liver. Administration of MAGICIAN could efficiently relieve the inflammation in the acute lung injury mouse model. In addition, MAGICIAN displayed good biosafety in systemic administration. The present study provides a safe and convenient approach for the clearance of cytokine storms, indicating the potential for clinical application in acute lung injury therapy.

Cell Membrane-Camouflaged Nanoparticles Mediated Nucleic Acids Delivery.

Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery.

Dose-Effect Relationship of Chitosan and Danshen Combined Injection for Fallopian Tube Recanalization.

Objectives: This study examined the dose-effect relationship of chitosan and danshen combined injections on the long-term prevention of fallopian tube re-obstructions, with increased pregnancy rates in infertile women. Methods: High-performance liquid chromatography was used to determine the content changes of combined chitosan and danshen injection. Two hundred and eighty patients with fallopian tube obstructions were randomly assigned to four groups. Group A (control group, saline), Group B (2 ml chitosan, 4 ml danshen), Group C (2 ml chitosan, 10 ml danshen), and Group D (1 ml chitosan, 10 ml danshen). Injections were administered after tubal recanalization. Results: The effective constituent of chitosan and danshen injection was stable. Tubal patency rate was 94.2% and 87.3% in Group C after 1 and 3 years, respectively, which was significantly higher than Groups A (38.6%, 31.5%), B (73.5%, 64.1%), and D (68.5%, 50.7%). Intrauterine pregnancy rates were 61.8% and 79.4% in Group C after 1 and 3 years, respectively, and were significantly higher than Groups A (31.8%, 34.8%), B (40.1%, 62.5%), and D (38.5%, 58.5%) (p < 0.05). Conclusion: Combined Chitosan and danshen injections prevented tubal obstruction and increased pregnancy rates for long periods using an optimal ratio of 1 part chitosan and 5 parts danshen.

PTPN18 Stimulates the Development of Ovarian Cancer by Activating the PI3K/AKT Signaling.

Objective: To illustrate the functions of protein tyrosine phosphatase nonreceptor type 18 (PTPN18) in the progression of ovarian cancer and the potential molecular mechanism. Methods: Differential PTPN18 expression in ovarian cancer samples was determined. Following PTPN18 knockdown, changes in proliferation and migration in ovarian cancer cells were detected. Nude mice with ovarian cancer were used to uncover the effects of PTPN18 on ovarian cancer growth in vivo. Results: PTPN18 was significantly upregulated in ovarian cancer samples and linked to pathological staging and metastasis rate. PTPN18 displayed prognostic and diagnostic potentials in ovarian cancer. Knockdown of PTPN18 and treatment of the PI3K inhibitor could inhibit proliferative and migratory abilities in ovarian cancer cells. Moreover, PTPN18 was capable of inactivating PI3K/AKT signaling. In vivo knockdown of PTPN18 suppressed ovarian cancer growth in nude mice. Conclusions: PTPN18 is upregulated in ovarian cancer, which stimulates the malignant development by activating PI3K/AKT signaling. The PTPN18 level is also associated with pathological staging and metastasis in ovarian cancer patients, which may be utilized as a hallmark predicting the malignant level.

A cellular senescence-related genes model allows for prognosis and treatment stratification of hepatocellular carcinoma: A bioinformatics analysis and experimental verification.

Introduction: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with low 5-year survival rate. Cellular senescence, characterized by permanent and irreversible cell proliferation arrest, plays an important role in tumorigenesis and development. This study aims to develop a cellular senescence-based stratified model, and a multivariable-based nomogram for guiding clinical therapy for HCC. Materials and methods: The mRNAs expression data of HCC patients and cellular senescence-related genes were obtained from TCGA and CellAge database, respectively. Through multiple analysis, a four cellular senescence-related genes-based prognostic stratified model was constructed and its predictive performance was validated through various methods. Then, a nomogram based on the model was constructed and HCC patients stratified by the model were analyzed for tumor mutation burden, tumor microenvironment, immune infiltration, drug sensitivity and immune checkpoint. Functional enrichment analysis was performed to explore potential biological pathways. Finally, we verified this model by siRNA transfection, scratch assay and Transwell Assay. Results: We established an cellular senescence-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of HCC patients in the ICGC database. The low and high risk score HCC patients stratified by the model showed different tumor mutation burden, tumor microenvironment, immune infiltration, drug sensitivity and immune checkpoint expressions. Functional enrichment analysis suggested several biological pathways related to the process and prognosis of HCC. Scratch assay and transwell assay indicated the promotion effects of the four cellular senescence-related genes (EZH2, G6PD, CBX8, and NDRG1) on the migraiton and invasion of HCC. Conclusion: We established a cellular senescence-based stratified model, and a multivariable-based nomogram, which could predict the survival of HCC patients and guide clinical treatment.