Fatty Acid Metabolism and Idiopathic Pulmonary Fibrosis

Fatty acid metabolism, including the de novo synthesis, uptake, oxidation, and derivation of fatty acids, plays several important roles at cellular and organ levels. Recent studies have identified characteristic changes in fatty acid metabolism in idiopathic pulmonary fibrosis (IPF) lungs, which implicates its dysregulation in the pathogenesis of this disorder. Here, we review the evidence for how fatty acid metabolism contributes to the development of pulmonary fibrosis, focusing on the profibrotic processes associated with specific types of lung cells, including epithelial cells, macrophages, and fibroblasts. We also summarize the potential therapeutics that target this metabolic pathway in treating IPF.

Blood-Derived Extracellular Vesicle-Associated miR-3182 Detects Non-Small Cell Lung Cancer Patients

With five-year survival rates as low as 3%, lung cancer is the most common cause of cancer-related mortality worldwide. The severity of the disease at presentation is accredited to the lack of early detection capacities, resulting in the reliance on low-throughput diagnostic measures, such as tissue biopsy and imaging. Interest in the development and use of liquid biopsies has risen, due to non-invasive sample collection, and the depth of information it can provide on a disease. Small extracellular vesicles (sEVs) as viable liquid biopsies are of particular interest due to their potential as cancer biomarkers. To validate the use of sEVs as cancer biomarkers, we characterised cancer sEVs using miRNA sequencing analysis. We found that miRNA-3182 was highly enriched in sEVs derived from the blood of patients with invasive breast carcinoma and NSCLC. The enrichment of sEV miR-3182 was confirmed in oncogenic, transformed lung cells in comparison to isogenic, untransformed lung cells. Most importantly, miR-3182 can successfully distinguish early-stage NSCLC patients from those with benign lung conditions. Therefore, miR-3182 provides potential to be used for the detection of NSCLC in blood samples, which could result in earlier therapy and thus improved outcomes and survival for patients.

Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants

SARS-CoV-2 is the most recently identified member of the betacoronavirus genus responsible for the COVID-19 pandemic. Repurposing of available drugs has been a “quick and dirty” approach to try to reduce mortality and severe symptoms in affected patients initially, and can still represent an undeniable and valuable approach to face COVID-19 as the continuous appearance and rapid diffusion of more “aggressive”/transmissible variants, capable of eluding antibody neutralization, challenges the effectiveness of some anti-SARS-CoV-2 vaccines.

Complement Inhibitors Vitronectin and Clusterin Are Recruited from Human Serum to the Surface of Coronavirus OC43-Infected Lung Cells through Antibody-Dependent Mechanisms

Little is known about the role of complement (C’) in infections with highly prevalent circulating human coronaviruses such as OC43, a group of viruses of major public health concern. Treatment of OC43-infected human lung cells with human serum resulted in C3 deposition on their surfaces and generation of C5a, indicating robust C’ activation. Real-time cell viability assays showed that in vitro C’-mediated lysis of OC43 infected cells requires C3, C5 and C6 but not C7, and was substantially delayed as compared to rapid C’-mediated killing of parainfluenza virus type 5 (PIV5)-infected cells. In cells co-infected with OC43 and PIV5, C’-mediated lysis was delayed, similar to OC43 infected cells alone, suggesting that OC43 infection induced dominant inhibitory signals. When OC43-infected cells were treated with human serum, their cell surfaces contained both Vitronectin (VN) and Clusterin (CLU), two host cell C’ inhibitors that can alter membrane attack complex (MAC) formation and C’-mediated killing. VN and CLU were not bound to OC43-infected cells after treatment with antibody-depleted serum. Reconstitution experiments with purified IgG and VN showed that human antibodies are both necessary and sufficient for VN recruitment to OC43-infected lung cells–novel findings with implications for CoV pathogenesis.

SARS-CoV-2 Omicron spike mediated immune escape, infectivity and cell-cell fusion

The Omicron variant emerged in southern Africa in late 2021 and is characterised by multiple spike mutations across all spike domains. Here we show that the Omicron spike confers very significant evasion of vaccine elicited neutralising antibodies that is more pronounced for ChAdOx-1 adenovirus vectored vaccine versus BNT162b2 mRNA vaccine. Indeed neutralisation of Omicron was not detectable for the majority of individuals who had received two doses of ChAdOx-1. Third dose mRNA vaccination rescues neutralisation in the short term. Despite three mutations predicted to favour spike S1/S2 cleavage, observed cleavage efficiency is lower than for wild type Wuhan-1 D614G and Delta. We demonstrate significantly lower infectivity of lung organoids and Calu-3 lung cells expressing endogenous levels of ACE2 and TMPRSS2 but similar infection as compared to Delta when using H1299 lung epithelial cells. Importantly, fusogenicity of the Omicron spike is impaired, leading to marked reduction in syncitia formation. These observations indicate that Omicron has gained immune evasion properties whilst possibly modulating properties associated with replication and pathogenicity.

Atovaquone and Berberine Chloride Reduce SARS-CoV-2 Replication In Vitro

Epidemic RNA viruses seem to arise year after year leading to countless infections and devastating disease. SARS-CoV-2 is the most recent of these viruses, but there will undoubtedly be more to come. While effective SARS-CoV-2 vaccines are being deployed, one approach that is still missing is effective antivirals that can be used at the onset of infections and therefore prevent pandemics. Here, we screened FDA-approved compounds against SARS-CoV-2. We found that atovaquone, a pyrimidine biosynthesis inhibitor, is able to reduce SARS-CoV-2 infection in human lung cells. In addition, we found that berberine chloride, a plant-based compound used in holistic medicine, was able to inhibit SARS-CoV-2 infection in cells through direct interaction with the virion. Taken together, these studies highlight potential avenues of antiviral development to block emerging viruses. Such proactive approaches, conducted well before the next pandemic, will be essential to have drugs ready for when the next emerging virus hits.

SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation, A Dynamical Mathematical Model

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL−1 s−1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5. To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

Immune Response towards COVID-19

Background: As the world witnessed the outbreak of coronavirus illness 2019 (COVID-19), a disorder developed as a result of a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), increasing genetics with healthcare evidence suggest a corresponding leadership to SARS as well as the Middle East Respiratory Syndrome (MERS). Aim: The aim of this review is to highlight Immune response of human body toward COVID-19. Materials and methods: This was a narrative review. A comprehensive literature search was done using PubMed, Google Scholar, Scopus, and EMBASE using the keywords, Immune Response; COVID-19; Vaccination; SARS-Cov-2; ACE2; Coronavirus; MERS. Results: A flow of viral components passes to the body by means of nostrils, mouth and eyes. SARS-CoV-2 is in a position to continue to become unnoticed extended than numerous influenza or coronaviruses. Its proteins can accomplish entry by unlocking the Angiotensin-Converting Enzyme 2 (ACE2) protein in the lung cells; viruses also possess antigens furthermore recognize that these are what cries the immunity into movement via making antibodies. Investigators demonstrate an extensive variety of immune cells respond to COVID-19 along with valuable source retrieval, discovering that might want to notify the manufacturing of a viable vaccination. Conclusion: The body's natural response to a viral infection is a non-invasive intrinsic response in which macrophages, neutrophils, and dendritic cells limit the virus's progression and may even prevent it by multiplying symptoms. This non-invasive solution is accompanied by an elastic response in which the body produces radicals that primarily adjust to the herpes virus.

Quantification and Characterization of Metals in Ultrafine Road Dust Particles

Road dust is an important source of resuspended particulate matter (PM) but information is lacking on the chemical composition of the ultrafine particle fraction (UFP; <0.1 µm). This study investigated metal concentrations in UFP isolated from the “dust box” of sweepings collected by the City of Toronto, Canada, using regenerative-air-street sweepers. Dust box samples from expressway, arterial and local roads were aerosolized in the laboratory and were separated into thirteen particle size fractions ranging from 10 nm to 10 µm (PM10). The UFP fraction accounted for about 2% of the total mass of resuspended PM10 (range 0.23–8.36%). Elemental analysis using ICP-MS and ICP-OES revealed a marked enrichment in Cd, Cr, Zn and V concentration in UFP compared to the dust box material (nano to dust box ratio ≥ 2). UFP from arterial roads contained two times more Cd, Zn and V and nine times more Cr than UFP from local roads. The highest median concentration of Zn was observed for the municipal expressway, attributed to greater volumes of traffic, including light to heavy duty vehicles, and higher speeds. The observed elevated concentrations of transition metals in UFP are a human health concern, given their potential to cause oxidative stress in lung cells.