Integrative metagenomic, transcriptomic, and proteomic analysis reveal the microbiota-host interplay in early-stage lung adenocarcinoma among non-smokers.

BACKGROUND: The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unknown. In this study, we systematically characterized the local microbial community and its associated features to enable early intervention. METHODS: A prospective collection of ES-LUAD samples (46 cases) and their corresponding normal tissues adjacent to the tumor (41 cases), along with normal lung tissue samples adjacent to pulmonary bullae in patients with spontaneous pneumothorax (42 cases), were subjected to ultra-deep metagenomic sequencing, host transcriptomic sequencing, and proteomic sequencing. The obtained omics data were subjected to both individual and integrated analysis using Spearman correlation coefficients. RESULTS: We concurrently detected the presence of bacteria, fungi, and viruses in the lung tissues. The microbial profile of ES-LUAD exhibited similarities to NAT but demonstrated significant differences from the healthy controls (HCs), characterized by an overall reduction in species diversity. Patients with ES-LUAD exhibited local microbial dysbiosis, suggesting the potential pathogenicity of certain microbial species. Through multi-omics correlations, intricate local crosstalk between the host and local microbial communities was observed. Additionally, we identified a significant positive correlation (rho > 0.6) between Methyloversatilis discipulorum and GOLM1 at both the transcriptional and protein levels using multi-omics data. This correlated axis may be associated with prognosis. Finally, a diagnostic model composed of six bacterial markers successfully achieved precise differentiation between patients with ES-LUAD and HCs. CONCLUSIONS: Our study depicts the microbial spectrum in patients with ES-LUAD and provides evidence of alterations in lung microbiota and their interplay with the host, enhancing comprehension of the pathogenic mechanisms that underlie ES-LUAD. The specific model incorporating lung microbiota can serve as a potential diagnostic tool for distinguishing between ES-LUAD and HCs.

Delivery of SAV-siRNA via Exosomes from Adipose-Derived Stem Cells for the Treatment of Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI) leads to cardiomyocyte death, poor cardiac remodeling, and heart failure, making it a major cause of mortality and morbidity. To restore cardiac pumping function, induction of cardiomyocyte regeneration has become a focus of academic interest. The Hippo pathway is known to regulate cardiomyocyte proliferation and heart size, and its inactivation allows adult cardiomyocytes to re-enter the cell cycle. METHODS: In this study, we investigated whether exosomes from adipose-derived stem cells (ADSCs) could effectively transfer siRNA for the Hippo pathway regulator Salvador (SAV) into cardiomyocytes to induce cardiomyocyte regeneration in a mouse model of MI. RESULTS: Our results showed that exosomes loaded with SAV-siRNA effectively transferred siRNA into cardiomyocytes and induced cardiomyocyte re-entry into the cell cycle, while retaining the previously demonstrated therapeutic efficacy of ADSC-derived exosomes to improve post-infarction cardiac function through anti-fibrotic, pro-angiogenic, and other effects. CONCLUSIONS: Our findings suggest that siRNA delivery via ADSC-derived exosomes may be a promising approach for the treatment of MI.

Role of competitive endogenous RNA networks in the pathogenesis of coronary artery disease.

BACKGROUND: The present study aimed to construct a network of competitive endogenous RNAs (ceRNAs) related to the pathogenesis of coronary artery disease (CAD), to provide a novel rationale for CAD treatment. METHODS: Bioinformatics methods were applied to screen for differentially expressed long non-coding RNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs) from the GSE68506, GSE59421, and GSE20129 datasets of the Gene Expression Omnibus (GEO) database. The miRcode database was used to predict lncRNA-binding miRNAs. The miRTarBase, miRDB, and TargetScan databases were used to predict the target genes of these miRNAs. An mRNA-miRNA-lncRNA ceRNA network of CAD was established. RESULTS: Between the CAD and normal control groups there were 264 DElncRNAs, 106 DEmiRNAs, and 1,879 DEmRNAs. We screened these differentially expressed gens (DEGs) respectively. There were 21 DElncRNAs, 13 DEmiRNAs, and 143 DEmRNAs in the ceRNA network by using Cytoscape application. The DEmRNAs were involved in the PI3K-Akt signaling pathway and the NF-κB signaling pathway. The key genes in the protein-protein interaction (PPI) network were HSP90AA1, CDKN1A, MCL1, MDM2, MAPK1, ABL1, LYN, CRK, CDK9, and FAS. CONCLUSIONS: The ceRNA network constructed in this study identified new candidate molecules for the treatment of CAD, providing some more comprehensive and higher-quality choices for the target treatment of CAD.

Screening and evaluation of the role of immune genes of brain metastasis in lung adenocarcinoma progression based on the TCGA and GEO databases.

BACKGROUND: Brain metastasis was one of the factors leading to the poor long-term prognosis of patients with lung adenocarcinoma (LUAD). METHODS: The expression levels of immune genes in LUAD and LUAD brain metastases tissues were analyzed in GSE161116 dataset using the GEO2R, and the levels of differential immune genes in normal lung and LUAD tissues were verified. The biological functions and signaling mechanisms of the differential immune genes were explored via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Cox regression analysis was used to screen the prognostic factors of LUAD patients, and a risk model was constructed. The role of the model was checked in the development of LUAD via receiver operating characteristic analysis, gene set enrichment analysis, and Cox regression analysis. RESULTS: Differentially expressed genes (DEGs) in brain metastasis were involved in the adaptive immune response, B cell differentiation, leukocyte migration, NF-kB signaling pathway, among others. The expression levels of TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 were independent factors affecting the poor prognosis of LUAD patients via Cox regression analysis and Akaike information criterion. In the constructed risk model, the overall survival of LUAD patients in the high-risk group was poor. The risk model was significantly related to the gender, clinical stage, T stage, lymph node metastasis, and survival status of LUAD patients. In addition, the risk model score was an independent risk factor that affected the poor prognosis of LUAD patients. TNFRSF11A, CAMP, F2RL1, IL11, MS4A1, and MS4A2 of the risk factors had diagnostic significance in LUAD brain metastasis and LUAD. The risk model participated in cytokinetic process, cell cycle, citrate cycle TCA cycle, etc. The risk model score was correlated with the levels of B cells memory, mast cells resting, macrophages M0, mast cells activated, neutrophils, eosinophils, T cells gamma delta, and immune cell markers. CONCLUSIONS: The risk model based on the LUAD brain metastasis immune factors TNFRSF11A, MS4A2, IL11, CAMP, MS4A1, and F2RL1 was related to the diagnosis, poor prognosis, and immune infiltrating cells of LUAD patients, and is expected to provide a reference for the development of treatment strategies for LUAD patients.

Porcupine inhibitor LGK­974 inhibits Wnt/ß­catenin signaling and modifies tumor­associated macrophages resulting in inhibition of the malignant behaviors of non­small cell lung cancer cells.

Tumor­associated macrophages (TAMs) are critical components of the tumor microenvironment that are tightly associated with malignancies in human cancers, including lung cancer. LGK­974, a small molecular inhibitor of Wnt secretion, was reported to block Wnt/ß­catenin signaling and exert anti­inflammatory effects by suppressing pro­inflammatory gene expression in cancer cells. Although it was reported that Wnt/ß­catenin was critical in regulating TAMs, it is still largely unknown whether LGK­974 regulates tumor malignancies by regulating TAMs. The present study firstly verified that the polarization of TAMs was regulated by LGK­974. LGK­974 increased M1 macrophage functional markers and decreased M2 macrophage functional markers. The addition of Wnt3a and Wnt5a, two canonical Wnt signaling inducers, reversed the decrease in M1 macrophage functional markers, including mannose receptor, IL­10 and Arg1, by activating Wnt/ß­catenin signaling. Conditioned medium from LGK­974­modified TAMs inhibited the malignant behaviors in A549 and H1299 cells, including proliferation, colony formation and invasion, by blocking Wnt/ß­catenin signaling. LGK­974­modified TAMs blocked the cell cycle at the G1/G0 phase, which was reversed by the addition of Wnt3a/5a, indicating that LGK­974 regulates the microenvironment by blocking Wnt/ß­catenin signaling. Taken together, the results indicate that LGK­974 indirectly inhibited the malignant behaviors of A549 and H1299 cells by regulating the inflammatory microenvironment by inhibiting Wnt/ß­catenin signaling in TAMs.

Evaluation of clinical value and potential mechanism of MTFR2 in lung adenocarcinoma via bioinformatics.

BACKGROUND: Mitochondrial fission regulator 2 (MTFR2) was involved in the progression and development of various cancers. However, the relationship between MTFR2 with lung adenocarcinoma (LUAD) had not been reported. Herein, this study analyzed the clinical significance and potential mechanisms of MTFR2 in LUAD via bioinformatics tools. RESULTS: We found that the level of MTFR2 was increased, and correlated with sex, age, smoking history, neoplasm staging, histological subtype and TP53 mutation status in LUAD patients. Kaplan-Meier survival analysis showed LUAD patients with increased MTFR2 had a poor prognosis. In addition, univariate COX regression analysis showed neoplasm staging, T stage, distant metastasis and MTFR2 level were risk factors for the prognosis of LUAD. A total of 1127 genes were coexpressed with MTFR2, including 840 positive and 208 negative related genes. KEGG and GSEA found that MTFR2 participated in the progression of LUAD by affecting cell cycle, DNA replication, homologous recombination, p53 signaling pathway and other mechanisms. The top 10 coexpressed genes, namely CDK1, CDC20, CCNB1, PLK1, CCNA2, AURKB, CCNB2, BUB1B, MAD2L1 and BUB1 were highly expressed, and were associated with poor prognosis in LUAD. CONCLUSIONS: Consequently, we elucidated MTFR2 was a biomarker for diagnosis and poor prognosis in LUAD, and might participate in the progression of LUAD via affecting cell cycle, DNA replication, homologous recombination and p53 signaling pathway.

Bilateral secondary pulmonary tuberculosis complicated with bilateral chylothorax: a case report.

A 26-year-old female was admitted to the emergency department of thoracic surgery complaining of chest tightness, shortness of breath, and a history of bilateral tuberculosis. A chest Computed Tomography (CT) scan showed bilateral pleural effusion. After that, the patient was implanted with bilateral intercostal drainage tubes. Further analysis of the pleural effusion was conducted to confirm the diagnosis of bilateral chylothorax. We initiated conservative treatment consisting of fasting and total parenteral nutrition. After the failure of conservative treatment, the patient underwent ligation of the thoracic duct by right-sided thoracotomy combined with talc slurry. On the first day postoperatively, the right pleural effusion had decreased significantly, while the left pleural effusion had not. Subsequently, talc slurry was injected into the left thoracic drainage tube of the patient. Bilateral pleural effusion was significantly reduced. Re-examination chest X-ray showed the disappearance of pleural effusion, and the patient was discharged good healthy. Chest X-rays were reexamined one month postoperatively, and the patient's lung was well dilated, with no recurrence of pleural effusion. In this case, it was shown that conservative treatment is the first choice for chylothorax. However, if this proves to be ineffective, early surgical treatment should be considered. Early diagnosis and timely surgical intervention are the key factors to improve the prognosis of patients.

Thoracic endometriosis: a case report and review of the literature.

Thoracic endometriosis is characterized by the presence of normal functioning endometrial tissues in normal pleural, diaphragm, or lung parenchyma, and main clinical symptoms include pneumothorax, menstrual hemothorax, menstrual hemoptysis, and pulmonary nodules. Chest X-ray (CXR), computed tomography (CT), magnetic resonance imaging (MRI), bronchoscopy, and surgical biopsy could be applied to the diagnosis of TE. Both drug therapy and surgical treatment were widely used to treat this disease, but no theory was used to guide the choice of treatment options. This paper introduces a case of menstrual hemoptysis due to endometriosis, and the final surgical treatment was chosen. The patient recovered well postoperatively and reported no hemoptysis during 2 months of follow-up. Reexamination of the chest through CT showed no ground-glass lesions or pulmonary exudative lesions. We make the following recommendations for patient selection when considering a surgical approach to the treatment of TE. Patients for whom surgery should be considered are those who (I) do not respond to drug therapy or relapse once drug therapy is withdrawn, (II) cannot tolerate drug therapy or who may wish to get pregnant in the near future (III) have limited lesions which are able to be completely removed during surgery. Patients in whom surgery is not recommended include those who have extensive lesions which cannot be surgically removed, including those with diaphragm or pleural involvement as the diseased tissues must be completely removed to avoid recurrence, and those who are unfit for surgery.