Hyperinsulinemia adversely affects lung structure and function

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly ( P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

Download Full-text

Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker

Biomolecules ◽

10.3390/biom11081197 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1197

Author(s):

Haoyu Yang ◽

Zixuan Xu ◽

Yuqian Peng ◽

Jiali Wang ◽

Yang Xiang

Keyword(s):

Signal Transduction ◽

Tumor Marker ◽

Tumor Invasion ◽

Epithelial Mesenchymal Transition ◽

Vital Role ◽

Structure And Function ◽

Mesenchymal Transition ◽

Tumor Tissues ◽

Integrin Β4 ◽

And Function

Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Many recent studies have shown that integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial–mesenchymal transition, and angiogenesis. Therefore, we categorize the research related to integrin β4, starting from its structure and function in tumor tissues, and provide a basic description. Based on its structure and function, we believe that integrin β4 can be used as a tumor marker. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors.

Download Full-text

CRISPR/Cas9 Genome Editing Tool: A Promising Tool for Therapeutic Applications on Respiratory Diseases

Current Gene Therapy ◽

10.2174/1566523220666201012145731 ◽

2020 ◽

Vol 20 (5) ◽

pp. 333-346

Author(s):

Sadiya Bi Shaikh ◽

Yashodhar Prabhakar Bhandary

Keyword(s):

Respiratory Diseases ◽

Gene Editing ◽

Epithelial Mesenchymal Transition ◽

Respiratory Health ◽

Chronic Obstructive ◽

Therapeutic Tool ◽

Obstructive Pulmonary Disease ◽

Mesenchymal Transition ◽

Chronic Respiratory Diseases ◽

Promising Tool

Respiratory diseases are one of the prime topics of concern in the current era due to improper diagnostics tools. Gene-editing therapy, like Clustered regularly interspaced palindromic repeats- associated nuclease 9 (CRISPR/Cas9), is gaining popularity in pulmonary research, opening up doors to invaluable insights on underlying mechanisms. CRISPR/Cas9 can be considered as a potential gene-editing tool with a scientific community that is helping in the advancement of knowledge in respiratory health and therapy. As an appealing therapeutic tool, we hereby explore the advanced research on the application of CRISPR/Cas9 tools in chronic respiratory diseases such as lung cancer, Acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF). We also address the urgent need to establish this gene-editing tool in various other lung diseases such as asthma, Chronic obstructive pulmonary disease (COPD) and Idiopathic pulmonary fibrosis (IPF). The present review introduces CRISPR/Cas9 as a worthy application in targeting epithelial-mesenchymal transition and fibrinolytic system via editing specific genes. Thereby, based on the efficiency of CRISPR/Cas9, it can be considered as a promising therapeutic tool in respiratory health research.

Download Full-text

EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

Technology in Cancer Research & Treatment ◽

10.1177/15330338211033077 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110330

Author(s):

Chuangui Chen ◽

Zhao Ma ◽

Hongjing Jiang

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Promoting Effect ◽

Migration Ability ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration ◽

And Function ◽

Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

Download Full-text

Lung ultrasound presentation of COVID-19 patients: phenotypes and correlations

Internal and Emergency Medicine ◽

10.1007/s11739-020-02620-9 ◽

2021 ◽

Author(s):

Gianmarco Secco ◽

◽

Marzia Delorenzo ◽

Francesco Salinaro ◽

Caterina Zattera ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Lung Ultrasound ◽

Structure And Function ◽

General Ward ◽

Prognostic Role ◽

Interstitial Syndrome ◽

Lung Structure ◽

And Function ◽

The Relationship

AbstractBedside lung ultrasound (LUS) can play a role in the setting of the SarsCoV2 pneumonia pandemic. To evaluate the clinical and LUS features of COVID-19 in the ED and their potential prognostic role, a cohort of laboratory-confirmed COVID-19 patients underwent LUS upon admission in the ED. LUS score was derived from 12 fields. A prevalent LUS pattern was assigned depending on the presence of interstitial syndrome only (Interstitial Pattern), or evidence of subpleural consolidations in at least two fields (Consolidation Pattern). The endpoint was 30-day mortality. The relationship between hemogasanalysis parameters and LUS score was also evaluated. Out of 312 patients, only 36 (11.5%) did not present lung involvment, as defined by LUS score < 1. The majority of patients were admitted either in a general ward (53.8%) or in intensive care unit (9.6%), whereas 106 patients (33.9%) were discharged from the ED. In-hospital mortality was 25.3%, and 30-day survival was 67.6%. A LUS score > 13 had a 77.2% sensitivity and a 71.5% specificity (AUC 0.814; p < 0.001) in predicting mortality. LUS alterations were more frequent (64%) in the posterior lower fields. LUS score was related with P/F (R2 0.68; p < 0.0001) and P/F at FiO2 = 21% (R2 0.59; p < 0.0001). The correlation between LUS score and P/F was not influenced by the prevalent ultrasound pattern. LUS represents an effective tool in both defining diagnosis and stratifying prognosis of COVID-19 pneumonia. The correlation between LUS and hemogasanalysis parameters underscores its role in evaluating lung structure and function.

Download Full-text