Bicarbonate: An Ancient Concept to Defeat Pathogens in Light of Recent Findings Beneficial for COVID-19 Patients?

Zsembery, Ákos; Kádár, Kristóf; Jaikumpun, Pongsiri; Deli, Mária A.; Jakab, Ferenc; Dobay, Orsolya

doi:10.2139/ssrn.3589403

Cited by 3 publications

(3 citation statements)

References 25 publications

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“…We could find the pathway Inflammatory mediator regulation of TRP channels enriched in Tables S-8 and S-6. This observation supports another possible line in the search for COVID-19 treatments [90,91].…”

Section: Analysis Of Cellular Transcriptional Response To Sars-cov-2 supporting

confidence: 82%

Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method

Lucchetta

Pellegrini

2020

Preprint

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Diseases imply dysregulation of cell’s functions at several levels. The study of differentially expressed genes in case-control cohorts of patients is often the first step in understanding the details of the cell’s dysregulation. A further level of analysis is introduced by noticing that genes are organized in functional modules (often called pathways), thus their action and their dysregulation may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method developed originally for detecting protein complexes in PPI networks, can be adapted to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the easier general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge of 2019. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover for the two cancer data sets, Core&Peel detects further nine relevant pathways enriched in the predicted disease module, not discovered by the other methods used in the comparative analysis. Finally we apply Core&Peel, along with other methods, to explore the transcriptional response of human cells to SARS-CoV-2 infection, at a modular level, aiming at finding supporting evidence for drug repositioning efforts.

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Section: Analysis Of Cellular Transcriptional Response To Sars-cov-2 supporting

confidence: 82%

Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method

Lucchetta

Pellegrini

2020

Preprint

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“…Besides, bicarbonate has chelating properties and can interact with calcium ion, which is an essential factor in the development of viral infections (when it is a free ion). Furthermore, bicarbonate, by decreasing calcium ion as a free ion and preventing lung acidification, protects the lung [ 59 ]. The normal pH of the airway surface liquid (ASL) is controlled by CFTR by transporting bicarbonate.…”

Section: Reactive Oxygen Species Non-dependent Pathwaysmentioning

confidence: 99%

“…Non-functional CFTR cannot transfer chloride, and pulmonary oedema ensues [53]. Conversely, bicarbonate ions are unable to enter the cells, and the pH may be disturbed [58][59][60] TGF Blocking NF-kB Bach1 Fig. 7 Pirfenidone activates peroxisome proliferator-activated receptors (alpha and gamma) (PPAR) [111,126].…”

Section: Therapeutic Role Of Pirfenidone By Regulation Of Nuclear Facmentioning

confidence: 99%

Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a theoretical perspective

2021

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pulmonary injury or multiple-organ injury by various pathological pathways. Transforming growth factor-beta (TGF-β) is a key factor that is released during SARS-CoV-2 infection. TGF-β, by internalization of the epithelial sodium channel (ENaC), suppresses the anti-oxidant system, downregulates the cystic fibrosis transmembrane conductance regulator (CFTR), and activates the plasminogen activator inhibitor 1 (PAI-1) and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kB). These changes cause inflammation and lung injury along with coagulopathy. Moreover, reactive oxygen species play a significant role in lung injury, which levels up during SARS-CoV-2 infection. Drug Suggestion Pirfenidone is an anti-fibrotic drug with an anti-oxidant activity that can prevent lung injury during SARS-CoV-2 infection by blocking the maturation process of transforming growth factor-beta (TGF-β) and enhancing the protective role of peroxisome proliferator-activated receptors (PPARs). Pirfenidone is a safe drug for patients with hypertension or diabetes and its side effect tolerated well. Conclusion The drug as a theoretical perspective may be an effective and safe choice for suppressing the inflammatory response during COVID-19. The recommendation would be a combination of pirfenidone and N -acetylcysteine to achieve maximum benefit during SARS-CoV-2 treatment.

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Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method

Lucchetta

Pellegrini

2020

Sci Rep

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Genes are organized in functional modules (or pathways), thus their action and their dysregulation in diseases may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method is used to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma, and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner, and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover, for the two cancer datasets, Core&Peel detects further eight relevant pathways not discovered by the other methods used in the comparative analysis. Finally, we apply Core&Peel and other methods to explore the transcriptional response of human cells to SARS-CoV-2 infection, finding supporting evidence for drug repositioning efforts at a pre-clinical level.

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Bicarbonate: An Ancient Concept to Defeat Pathogens in Light of Recent Findings Beneficial for COVID-19 Patients?

Cited by 3 publications

References 25 publications

Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method

Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method

Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a theoretical perspective

Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method

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