Human Lung
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2021 ◽  
Vol 226 ◽  
pp. 112837
Sheng Yang ◽  
Yanping Cheng ◽  
Zaozao Chen ◽  
Tong Liu ◽  
Lihong Yin ◽  

2021 ◽  
Yan Zhang ◽  
Lei Kang ◽  
Claudia Tung Kei Lo ◽  
Terence T.W. Wong

Histopathology based on formalin-fixed and paraffin-embedded tissues remains the gold standard for surgical margin assessment (SMA). However, routine pathological practice is lengthy and laborious, failing to provide immediate feedback to surgeons and pathologists for intraoperative decision-making. In this report, we propose a cost-effective and easy-to-use histological imaging method with speckle illumination microscopy (i.e., HiLo). HiLo can achieve rapid and non-destructive imaging of large and fluorescently-labelled resection tissues at an acquisition speed of 5 cm2/min with 1.3-μm lateral resolution and 5.8-μm axial resolution, demonstrating a great potential as an intraoperative SMA tool that can be used by surgeons and pathologists to detect residual tumors at surgical margins. It is experimentally validated that HiLo enables rapid diagnosis of different subtypes of human lung adenocarcinoma and hepatocellular carcinoma, producing images with remarkably recognizable cellular features comparable to the gold-standard histology. This work will facilitate the clinical translations of HiLo microscopy to improve the current standard-of-care.

Amrutha Arjunan ◽  
Sankar Pajaniradje ◽  
Arul Prakash Francis ◽  
Srividya Subramanian ◽  
Sathyapriya Chandramohan ◽  

2021 ◽  
Jing Lv ◽  
Shibing Zhu ◽  
Huiping Chen ◽  
Ying Xu ◽  
Qingyu Su ◽  

2021 ◽  
Parimal Karmakar ◽  
Sougata Ghosh Chowdhury ◽  
Rachayeeta Ray ◽  
Debalina Bhattacharya

Abstract Exosomes are one type of small extracellular vesicles having a size range of 30–150 nm and secreted by the endosomal compartment of most eukaryotic cells. It has been found that exosomes can serve as a communicating vehicle to transfer information among cells and thus can be associated with numerous physiological and pathological functions. In this study, we have isolated exosomes from two different human cancer cell lines. Isolated exosomes were characterized by scanning electron microscopy, DLS and by western blotting. It was observed that exosomes isolated from mock treated human lung epithelial carcinoma (A549) cells or Hela cells exerted growth arrest to the human prostate carcinoma (PC3) cells, but no growth arrest was observed in case of normal human lung fibroblast cell line (WI38). Additionally, exosomes isolated from PC3 cells have no effect on PC3 cells. This is also true for exosomes isolated from H2O2 induced senescent human lung cancer cells (A549). Analysis of exosome content by western blotting reveals the presence of PTEN in the exosome of lung cancer cells. Functional analysis of PTEN pathways in PC3 cells indicates the inactivation of Akt in exosome treated cells. Therefore, from our study we have concluded that exosomes secreted from A549 cells which contain functional PTEN, may be used for delivery of PTEN to cancer cells without functional PTEN.

2021 ◽  
Vol 12 ◽  
KM Roach ◽  
E Castells ◽  
K Dixon ◽  
S Mason ◽  
G Elliott ◽  

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease with a poor prognosis and increasing incidence. Pirfenidone and nintedanib are the only approved treatments for IPF but have limited efficacy and their mechanisms of action are poorly understood. Here we have examined the effects of pirfenidone and nintedanib in a human model of lung fibrogenesis, and compared these with the putative anti-fibrotic compounds Lipoxin A4 (LXA4), and senicapoc, a KCa3.1 ion channel blocker.Methods: Early fibrosis was induced in cultured human lung parenchyma using TGFβ1 for 7 days, ± pirfenidone, nintedanib, or LXA4. Pro-fibrotic responses were examined by RT-PCR, immunohistochemistry and soluble collagen secretion.Results: Thirty six out of eighty four IPF and fibrosis-associated genes tested were significantly upregulated by TGFβ1 in human lung parenchyma with a ≥0.5 log2FC (n = 32). Nintedanib (n = 13) reduced the mRNA expression of 14 fibrosis-associated genes including MMPs (MMP1,−4,−13,−14), integrin α2, CXCR4 and PDGFB, but upregulated α-smooth muscle actin (αSMA). Pirfenidone only reduced mRNA expression for MMP3 and −13. Senicapoc (n = 11) previously attenuated the expression of 28 fibrosis-associated genes, including αSMA, several growth factors, collagen type III, and αV/β6 integrins. Pirfenidone and nintedanib significantly inhibited TGFβ1-induced fibroblast proliferation within the tissue, but unlike senicapoc, neither pirfenidone nor nintedanib prevented increases in tissue αSMA expression. LXA4 was ineffective.Conclusions: Pirfenidone and nintedanib demonstrate modest anti-fibrotic effects and provide a benchmark for anti-fibrotic activity of new drugs in human lung tissue. Based on these data, we predict that the KCa3.1 blocker senicapoc will show greater benefit than either of these licensed drugs in IPF.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1656
Jiapeng Li ◽  
Shuhan Liu ◽  
Jian Shi ◽  
Hao-Jie Zhu

ProTide technology is a powerful tool for the design of nucleoside/nucleotide analog prodrugs. ProTide prodrug design improves cell permeability and enhances intracellular activation. The hydrolysis of the ester bond of a ProTide is a determinant of the intracellular activation efficiency and final antiviral efficacy of the prodrug. The hydrolysis is dictated by the catalytic activity and abundance of activating enzymes. The antiviral agents tenofovir alafenamide (TAF) and sofosbuvir (SBV) are typical ProTides. Both TAF and SBV have also been proposed to treat patients with COVID-19. However, the mechanisms underlying the activation of the two prodrugs in the lung remain inconclusive. In the present study, we profiled the catalytic activity of serine hydrolases in human lung S9 fractions using an activity-based protein profiling assay. We evaluated the hydrolysis of TAF and SBV using human lung and liver S9 fractions and purified enzymes. The results showed that CatA and CES1 were involved in the hydrolysis of the two prodrugs in the human lung. More specifically, CatA exhibited a nearly 4-fold higher hydrolytic activity towards TAF than SBV, whereas the CES1 activity on hydrolyzing TAF was slightly lower than that for SBV. Overall, TAF had a nearly 4-fold higher hydrolysis rate in human lung S9 than SBV. We further analyzed protein expression levels of CatA and CES1 in the human lung, liver, and primary cells of the two tissues using proteomics data extracted from the literature. The relative protein abundance of CatA to CES1 was considerably higher in the human lung and primary human airway epithelial cells than in the human liver and primary human hepatocytes. The findings demonstrated that the high susceptivity of TAF to CatA-mediated hydrolysis resulted in efficient TAF hydrolysis in the human lung, suggesting that CatA could be utilized as a target activating enzyme when designing antiviral ester prodrugs for the treatment of respiratory virus infection.

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2713
Gaowa Saren ◽  
Aaron Wong ◽  
Yun-Bi Lu ◽  
Cristina Baciu ◽  
Wenyong Zhou ◽  

Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.

Xiaowen Hu ◽  
Kandasamy Saravanakumar ◽  
Anbazhagan Sathiyaseelan ◽  
Vinothkumar Rajamanickam ◽  
Myeong-Hyeon Wang

2021 ◽  
pp. 100125
Mariana Morozesk ◽  
Iara da Costa Souza ◽  
Marisa Narciso Fernandes ◽  
Daniel Cristian Ferreira Soares

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