Misdiagnosis of primary mucosa-associated lymphoid tissue lymphoma of the pleura: case report and literature review.

Background: Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B cell lymphoma. Its occurrence in the pleura is rare, with atypical clinical manifestations. MALT of the pleura is easily misdiagnosed. This is the first case report of pleural MALT lymphoma in China. Case Description: We report the case of a 54-year-old Chinese man with no notable medical history who complained of cough, sputum, and shortness of breath for 3 months. He had a positive purified protein derivative (PPD) test. An initial misdiagnosis of pleural tuberculosis was corrected, after 3 thoracoscopic biopsies and tests, to primary pleural MALT lymphoma. He received treatments of R-CHOP (rituximab, cyclophosphamide, epirubicin, vindesine and prednisolone) and traditional Chinese medicine. The patient was followed for 3 years until June 2022, with no obvious respiratory symptoms. Pleural MALT lymphoma is extremely rare, with only a few cases reported. This article describes our case, and includes an overview of 15 previously reported cases to summarize the characteristics, treatments, and prognosis of primary pleural MALT lymphoma. Conclusions: Pleural MALT lymphoma is rare, and a correct diagnosis depends on tissue biopsy, immunohistochemical staining, and detection of gene rearrangement. Thoracoscopy is important to diagnose this disease. Multiple thoracoscopic biopsies may be necessary.

Construction of ceRNA network to identify the lncRNA and mRNA related to non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) harms human health, but its pathogenesis remains unclear. We wish to provide more molecular therapeutic targets for NSCLC. METHODS: The NSCLC tissue and normal tissue samples were screened for genetic comparison in the TCGA database. The predicted lncRNA and mRNA in BEAS2B and A549 cells were detected. RESULTS: Volcano plot displayed differentially expressed lncRNAs and mRNAs in adjacent tissues and NSCLC tissues. The survival curve showed that the lncRNA and mRNA had a significant impact on the patient's survival. The results of GO term enrichment analysis indicated that mRNA functions were enriched in cell cycle-related pathways. In the ceRNA interaction network, 13 lncRNAs and 20 miRNAs were found to have an interactive relationship. Finally, 3 significantly different lncRNAs (LINC00968, lnc-FAM92A-9 and lnc-PTGFR-1) and 6 mRNAs (CTCFL, KRT5, LY6D, TMEM, GBP6, and TMEM179) with potential therapeutic significance were screened out. And the cell experiment verified our results. CONCLUSION: We screened out clinically significant 3 lncRNAs and 6 mRNAs involved in the ceRNA network, which were the key to our future research on the treatment of NSCLC.

Bioinformatics prediction of differential miRNAs in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. The drug resistance of NSCLC has clinically increased. This study aimed to screen miRNAs associated with NSCLC using bioinformatics analysis. We hope that the screened miRNA can provide a research direction for the subsequent treatment of NSCLC. METHODS: We screened out the common miRNAs after compared the NSCLC-related genes in the TCGA database and GEO database. Selected miRNA was performed ROC analysis, survival analysis, and enrichment analysis (GO term and KEGG pathway). RESULTS: A total of 21 miRNAs were screened in the two databases. And they were all highly expressed in normal and low in cancerous tissues. Hsa-mir-30a was selected by ROC analysis and survival analysis. Enrichment analysis showed that the function of hsa-mir-30a is mainly related to cell cycle regulation and drug metabolism. CONCLUSION: Our study found that hsa-mir-30a was differentially expressed in NSCLC, and it mainly affected NSCLC by regulating the cell cycle and drug metabolism.

Robust Prediction of Immune Checkpoint Inhibition Therapy for Non-Small Cell Lung Cancer.

Background: The development of immune checkpoint inhibitors (ICIs) is a revolutionary milestone in the field of immune-oncology. However, the low response rate is the major problem of ICI treatment. The recent studies showed that response rate to single-agent programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibition in unselected non-small cell lung cancer (NSCLC) patients is 25% so that researchers defined several biomarkers to predict the response of immunotherapy in ICIs treatment. Common biomarkers like tumor mutational burden (TMB) and PD-L1 expression have several limitations, such as low accuracy and inadequately validated cutoff value. Methods: Two published and an unpublished ICIs treatment NSCLC cohorts with 129 patients were collected and divided into a training cohort (n = 53), a validation cohort (n = 22), and two independent test cohorts (n = 34 and n = 20). We identified six immune-related pathways whose mutational status was significantly associated with overall survival after ICIs treatment. Then these pathways mutational status combined with TMB, PD-L1 expression and intratumor heterogeneity were incorporated to build a Bayesian-regularization neural networks (BRNN) model to predict the ICIs treatment response. Results: We firstly proved that TMB, PD-L1, and mutant-allele tumor heterogeneity (MATH) were independent biomarkers. The survival analysis of six immune-related pathways revealed the mutational status could distinguish overall survival after ICIs treatment. When predicting immunotherapy efficacy, the overall accuracy of area under curve (AUC) in validation cohort reaches 0.85, outperforming previous predictors in either sensitivity or specificity. And the AUC in two independent test cohorts reach 0.74 and 0.80. Conclusion: We developed a pathway-model that could predict the efficacy of ICIs in NSCLC patients. Our study made a significant contribution to solving the low prediction accuracy of immunotherapy of single biomarker. With the accumulation of larger data sets, further studies are warranted to refine the predictive performance of the approach.

Notch1 regulates endothelial apoptosis via the ERK pathway in chronic obstructive pulmonary disease.

The Notch signaling pathway plays critical role for determining cell fate by controlling proliferation, differentiation, and apoptosis. In the current study, we investigated the roles of the Notch signaling pathway in cigarette smoke (CS)-induced endothelial apoptosis in chronic obstructive pulmonary disease (COPD). We obtained surgical specimens from 10 patients with COPD and 10 control participants. Notch1, 2, and 4 express in endothelial cells, whereas Notch3 mainly localizes in smooth muscle cells. Compared with control groups, we found that the expression of Notch1, 3, and 4 decreased, as well as their target genes Hes1 and Hes2, while the expression of Notch2 and extracellular signal-regulated kinase (ERK)1/2 increased in COPD patients compared with controls, as well as in human pulmonary microvascular endothelial cells (HPMECs) when exposed to CS extract (CSE). Overexpression of Notch1 with N1ICD in HPMECs markedly alleviated the cell apoptosis induced by CSE. The ERK signaling pathway was significantly activated by CSE, which correlated with CSE-induced apoptosis. However, this activation can be abolished by N1ICD overexpression. Furthermore, treatment of PD98059 (ERK inhibitor) significantly alleviated CSE-induced apoptosis, as well as reduced the methylation of mitochondrial transcription factor A (mtTFA) promoter, which was correlated with CS-induced endothelial apoptosis. These results suggest that CS alters Notch signaling in pulmonary endothelial cells. Notch1 protects against CS-induced endothelial apoptosis in COPD through inhibiting the ERK pathway, while the ERK pathway further regulates the methylation of mtTFA promotor.

NOTCH signaling in lung diseases.

NOTCH is a fundamental signaling system that regulates normal embryonic development and tissue homeostasis in adult life. NOTCH receptor is a single-pass transmembrane protein normally triggered via direct cell-to-cell contact, in which NOTCH ligands bind the extracellular domain of the receptor, inducing γ-secretase cleavage and release of intracellular domain. The intracellular domain binds to the transcriptional effector RBPJκ to activate transcription of target genes that regulate cell differentiation, patterning, and morphogenesis during embryonic development and adult life. Specifically, NOTCH plays an essential role in the development and homeostasis of the lung. Aberrations in NOTCH signaling or components of the signaling system have been linked to various pulmonary pathological conditions. We herein provide a brief overview of collective in vitro and in vivo studies of NOTCH signaling to illustrate its regulatory functions in lung diseases, including asthma, chronic obstructive pulmonary disease, pulmonary arterial hypertension, and lung cancer. We also discuss the mechanisms underlying the regulatory role of NOTCH in these pathological conditions and the potential of NOTCH-targeted therapies for the treatment of these diseases.

Curcumin induces autophagy via activating the AMPK signaling pathway in lung adenocarcinoma cells.

Curcumin is a major yellow pigment and active component of turmeric widely used as dietary spice and herbal medicine. This compound has been reported to be a promising antitumor agent, although the underlying molecular mechanisms are not fully understood yet. In this study, we reported that curcumin inhibited growth of lung adenocarcinoma cells, but had no cytotoxic activity to IMR-90 normal lung fibroblast cells. Curcumin induced autophagy in the A549 human lung adenocarcinoma cell line, evidenced by LC3 immunofluorescence analysis and immunoblotting assays on LC3 and SQSTM1. Moreover, the autophagy inhibitor 3-MA partly blocked the inhibitory effect of curcumin on the growth of A549 cells. Curcumin markedly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetylCoA carboxylase in A549 cells. At last, pharmacological blockade of the AMPK signaling pathway by compound C and genetic disruption of the AMPK signaling pathway with siRNA-mediated AMPKα1 knockdown impaired the autophagy-inducing effect of curcumin. Collectively, our data suggests that curcumin induces autophagy via activating the AMPK signaling pathway and the autophagy is important for the inhibiting effect of curcumin in lung adenocarcinoma cells.

Sirt3 is a tumor suppressor in lung adenocarcinoma cells.

Sirt3, a member of the mammalian sirtuin family protein that is localized to mitochondria, is a NAD+-dependent deacetylase and plays an important role in the control of metabolic activity. Recently, several studies have shown the potential role of Sirt3 in certain types of tumors such as breast cancer and hepatocellular carcinoma. However, the role of Sirt3 in lung adenocarcinoma has never been studied. In the present study, we found that Sirt3 protein expression was downregulated in human lung adenocarcinoma tissue when compared with that in adjacent normal tissue. Overexpression of Sirt3 using adenovirus significantly inhibited the growth of the A549 lung adenocarcinoma cell line. In this cell line, overexpression of Sirt3 induced apoptosis, which was evidenced by Annexin V + PI assay and cleaved caspase-3 immunoblotting. Furthermore, overexpression of Sirt3 increased the bax/bcl-2 and bad/bcl-x/L ratios, and promoted AIF translocation to the nucleus. Finally, Sirt3 overexpression upregulated p53 and p21 protein levels, and decreased intracellular ROS levels. Collectively, our data suggest that Sirt3 is a tumor suppressor in lung adenocarcinoma development and progression and may be a promising therapeutic target for lung adenocarcinoma.

[Comparision of several different peritoneal fibrosis rat models].

OBJECTIVE: To compare different types of peritoneal fibrosis models in rats. METHODS: Thirty-four SD rats were divided into 5 groups: control group (Group 1), normal saline group (Group 2), high glucose group (4.25% peritoneal dialysate, 4.25% PDF, Group 3), high glucose + lipopolysaceharides (LPS) group (4.25% PDF + LPS, Group 4), high glucose + erythromycin group (4.25% PDF + lactobionate erythromycin, Group 5). A 2-hour peritoneal equilibration test (PET) was performed after 5 weeks. Then animals were humanely killed. Dialysate-to-plasma urea ratio (D/ Purea), glucose reabsorption (D2/D0), net ultrafiltration (UF) volume were determined. The level of fibronectin in peritoneal tissues was measured by immunohistochemical method. Peritoneal membrane histology was evaluated by light microscopy. RESULTS: The D2/D0 ratio and net ultrafiltration volume in Groups 3, 4, and 5 were significantly lower than those in Groups 1 and 2 (P < 0.05) . The D/Purea ratio in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0. 05 ). The level of fibronectin in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0.05 ). CONCLUSION: Different types of peritoneal fibrosis models in rats has been established. The best model is high clusion glucose + erythromycin.