scholarly journals Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage

2021 ◽  
Vol 12 ◽  
Author(s):  
Saad A. Khan ◽  
Kayla F. Goliwas ◽  
Jessy S. Deshane
Keyword(s):  
De Novo ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Lung Damage ◽  
Lung Pathology ◽  
Cytokine Storm ◽  
Bioactive Lipids ◽  
Chronic Lung Diseases ◽  
Sphingosine 1 Phosphate ◽  
Novel Coronavirus

Sphingolipids are bioactive lipids involved in the regulation of cell survival, proliferation, and the inflammatory response. The SphK/S1P/S1PR pathway (S1P pathway) is a driver of many anti-apoptotic and proliferative processes. Pro-survival sphingolipid sphingosine-1-phosphate (S1P) initiates its signaling cascade by interacting with various sphingosine-1-phosphate receptors (S1PR) through which it is able to exert its pro-survival or inflammatory effects. Whereas sphingolipids, including ceramides and sphingosines are pro-apoptotic. The pro-apoptotic lipid, ceramide, can be produced de novo by ceramide synthases and converted to sphingosine by way of ceramidases. The balance of these antagonistic lipids and how this balance manifests is the essence of the sphingolipid rheostat. Recent studies on SARS-CoV-2 have implicated the S1P pathway in the pathogenesis of novel coronavirus disease COVID-19-related lung damage. Accumulating evidence indicates that an aberrant inflammatory process, known as “cytokine storm” causes lung injury in COVID-19, and studies have shown that the S1P pathway is involved in signaling this hyperinflammatory response. Beyond the influence of this pathway on cytokine storm, over the last decade the S1P pathway has been investigated for its role in a wide array of lung pathologies, including pulmonary fibrosis, pulmonary arterial hypertension (PAH), and lung cancer. Various studies have used S1P pathway modulators in models of lung disease; many of these efforts have yielded results that point to the potential efficacy of targeting this pathway for future treatment options. Additionally, they have emphasized S1P pathway’s significant role in inflammation, fibrosis, and a number of other endothelial and epithelial changes that contribute to lung damage. This review summarizes the S1P pathway’s involvement in COVID-19 and chronic lung diseases and discusses the potential for targeting S1P pathway as a therapeutic option for these diseases.

scholarly journals Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues

Metabolites ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 473
Author(s):  
Yue Hei Leung ◽  
Sonja Christiane Bäßler ◽  
Christian Koch ◽  
Theresa Scheu ◽  
Ulrich Meyer ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
De Novo ◽  
Specific Activity ◽  
Multiple Reaction Monitoring ◽  
De Novo Synthesis ◽  
Bioactive Lipids ◽  
Tissue Specific ◽  
Sphingosine 1 Phosphate ◽  
Ceramide Accumulation ◽  
Subcutaneous Adipose

Sphingolipids are bioactive lipids that can modulate insulin sensitivity, cellular differentiation, and apoptosis in a tissue-specific manner. However, their comparative profiles in bovine retroperitoneal (RPAT) and subcutaneous adipose tissue (SCAT) are currently unknown. We aimed to characterize the sphingolipid profiles using a targeted lipidomics approach and to assess whether potentially related sphingolipid pathways are different between SCAT and RPAT. Holstein bulls (n = 6) were slaughtered, and SCAT and RPAT samples were collected for sphingolipid profiling. A total of 70 sphingolipid species were detected and quantified by UPLC-MS/MS in multiple reaction monitoring (MRM) mode, including ceramide (Cer), dihydroceramide (DHCer), sphingomyelin (SM), dihydrosphingomyelin (DHSM), ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), galactosylceramide (GalCer), glucosylceramide (GluCer), lactosylceramide (LacCer), sphinganine (DHSph), and sphingosine (Sph). Our results showed that sphingolipids of the de novo synthesis pathway, such as DHSph, DHCer, and Cer, were more concentrated in RPAT than in SCAT. Sphingolipids of the salvage pathway and the sphingomyelinase pathway, such as Sph, S1P, C1P, glycosphingolipid, and SM, were more concentrated in SCAT. Our results indicate that RPAT had a greater extent of ceramide accumulation, thereby increasing the concentration of further sphingolipid intermediates in the de novo synthesis pathway. This distinctive sphingolipid distribution pattern in RPAT and SCAT can potentially explain the tissue-specific activity in insulin sensitivity, proinflammation, and oxidative stress in RPAT and SCAT.

scholarly journals Cytokine Storm in the Novel Coronavirus Infection and Methods of its Correction

2021 ◽  
Vol 65 (11-12) ◽  
pp. 27-37
Author(s):  
A. V. Ershov ◽  
V. D. Surova ◽  
V. T. Dolgikh ◽  
T. I. Dolgikh
Keyword(s):  
Fatal Outcome ◽  
Lung Damage ◽  
The Novel ◽  
Cytokine Storm ◽  
Leading Role ◽  
Average Impact ◽  
Average Impact Factor ◽  
Coronavirus Infection ◽  
Novel Coronavirus

The aim of the study was to identify the role of cytokine storm in COVID-19, that emerged at the end of 2019, based on the analysis of 80 publications, including 17.4% Russian and 82.6% foreign publications for 2014–2020 with an average impact factor of 11.94 and a maximum of 74.699. This review includes an in-depth discussion of the possible causes and pathogenetic factors of cytokine storm syndrome development caused by COVID-19. The results of research on the use of various principles of cytokine storm correction are provided. It has been established that lung damage and the development of a fatal outcome are caused not by the virus itself, but by the hyperreaction of the body's immune system. The leading role in this process belongs to the cytokine storm, including the action of IL-6.

scholarly journals The pulmonary pathology of COVID-19

2021 ◽  
Vol 478 (1) ◽  
pp. 137-150
Author(s):  
Hans Bösmüller ◽  
Matthias Matter ◽  
Falko Fend ◽  
Alexandar Tzankov
Keyword(s):  
Viral Infections ◽  
Diffuse Alveolar Damage ◽  
High Viral Load ◽  
Lung Damage ◽  
Disease Stage ◽  
Lung Pathology ◽  
Open Questions ◽  
Cytokine Levels ◽  
Novel Coronavirus ◽  
Disease Stages

AbstractThe lung is the main affected organ in severe coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2, and lung damage is the leading cause of death in the vast majority of patients. Mainly based on results obtained by autopsies, the seminal features of fatal COVID-19 have been described by many groups worldwide. Early changes encompass edema, epithelial damage, and capillaritis/endothelialitis, frequently combined with microthrombosis. Subsequently, patients with manifest respiratory insufficiency exhibit exudative diffuse alveolar damage (DAD) with hyaline membrane formation and pneumocyte type 2 hyperplasia, variably complicated by superinfection, which may progress to organizing/fibrotic stage DAD. These features, however, are not specific for COVID-19 and can be found in other disorders including viral infections. Clinically, the early disease stage of severe COVID-19 is characterized by high viral load, lymphopenia, massive secretion of pro-inflammatory cytokines and hypercoagulability, documented by elevated D-dimers and an increased frequency of thrombotic and thromboembolic events, whereas virus loads and cytokine levels tend to decrease in late disease stages, when tissue repair including angiogenesis prevails. The present review describes the spectrum of lung pathology based on the current literature and the authors’ personal experience derived from clinical autopsies, and tries to summarize our current understanding and open questions of the pathophysiology of severe pulmonary COVID-19.

scholarly journals Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes

2020 ◽  
Author(s):  
Rajendra Karki ◽  
Bhesh Raj Sharma ◽  
Shraddha Tuladhar ◽  
Evan Peter Williams ◽  
Lillian Zalduondo ◽  
...  
Keyword(s):  
Cell Death ◽  
Tissue Damage ◽  
Inflammatory Cell ◽  
Treatment Options ◽  
Lung Damage ◽  
Caspase 8 ◽  
Cytokine Storm ◽  
Tnf Α ◽  
Ifn Γ

SUMMARYThe COVID-19 pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options and an urgent need to understand the pathogenesis of multi-organ failure and lung damage. Cytokine storm is associated with severe inflammation and organ damage during COVID-19. However, a detailed molecular pathway defining this cytokine storm is lacking, and gaining mechanistic understanding of how SARS-CoV-2 elicits a hyperactive inflammatory response is critical to develop effective therapeutics. Of the multiple inflammatory cytokines produced by innate immune cells during SARS-CoV-2 infection, we found that the combined production of TNF-α and IFN-γ specifically induced inflammatory cell death, PANoptosis, characterized by gasdermin-mediated pyroptosis, caspase-8-mediated apoptosis, and MLKL-mediated necroptosis. Deletion of pyroptosis, apoptosis, or necroptosis mediators individually was not sufficient to protect against cell death. However, cells deficient in both RIPK3 and caspase-8 or RIPK3 and FADD were resistant to this cell death. Mechanistically, the JAK/STAT1/IRF1 axis activated by TNF-α and IFN-γ co-treatment induced iNOS for the production of nitric oxide. Pharmacological and genetic deletion of this pathway inhibited pyroptosis, apoptosis, and necroptosis in macrophages. Moreover, inhibition of PANoptosis protected mice from TNF-α and IFN-γ-induced lethal cytokine shock that mirrors the pathological symptoms of COVID-19. In vivo neutralization of both TNF-α and IFN-γ in multiple disease models associated with cytokine storm showed that this treatment provided substantial protection against not only SARS-CoV-2 infection, but also sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock models, demonstrating the broad physiological relevance of this mechanism. Collectively, our findings suggest that blocking the cytokine-mediated inflammatory cell death signaling pathway identified here may benefit patients with COVID-19 or other cytokine storm-driven syndromes by limiting inflammation and tissue damage. The findings also provide a molecular and mechanistic description for the term cytokine storm. Additionally, these results open new avenues for the treatment of other infectious and autoinflammatory diseases and cancers where TNF-α and IFN-γ synergism play key pathological roles.

scholarly journals Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues

2020 ◽  
Author(s):  
Yue Hei Leung ◽  
Sonja Baessler ◽  
Christian Koch ◽  
Theresa Scheu ◽  
Ulrich Meyer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
De Novo ◽  
Specific Activity ◽  
Lipolytic Activity ◽  
Bioactive Lipids ◽  
Tissue Specific ◽  
Sphingosine 1 Phosphate ◽  
Ceramide Accumulation ◽  
Subcutaneous Adipose

Abstract Background: Sphingolipids are bioactive lipids that can modulate insulin sensitivity, cellular differentiation, and apoptosis in a tissue-specific manner. Previous studies in dairy cattle reported that the retroperitoneal adipose tissue (RPAT) was more active than the subcutaneous adipose tissue (SCAT) in terms of insulin sensitivity, lipolytic activity, and pro-inflammatory signaling. Sphingolipids were discussed to be involved in inflammation, however, their comparative profiles in bovine RPAT and SCAT are currently unknown. We aimed to characterize the sphingolipid profiles using a targeted lipidomics approach and to assess whether potentially related sphingolipid pathways are different between SCAT and RPAT. Holstein bulls (n = 6) were slaughtered, and SCAT and RPAT samples were collected for sphingolipid profiling. A total of 70 sphingolipid species were detected, including 24 species of ceramide (Cer) and dihydroceramide (DHCer), 18 species of sphingomyelin (SM) and dihydrosphingomyelin (DHSM), 11 species of ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P), 9 species of galactosylceramide (GalCer), glucosylceramide (GluCer), lactosylceramide (LacCer), and 8 species of sphinganine (DHSph) and sphingosine (Sph). The concentration of each sphingolipid was quantified by UPLC-MRM/MS. Results: Our results showed that sphingolipids of the de novo synthesis pathway such as DHSph, DHCer, and Cer, were more concentrated in RPAT than in SCAT. Sphingolipids of the salvage pathway and the sphingomyelinase pathway such as Sph, S1P, C1P, glycosphingolipid, and SM were more concentrated in SCAT. Our results indicate that RPAT had a greater extent of ceramide accumulation, and thereby increased the concentration of further sphingolipid intermediates in the de novo synthesis pathway.Conclusion: This distinctive sphingolipid distribution pattern in RPAT and SCAT can potentially explain the tissue-specific activity in insulin sensitivity, pro-inflammation, and oxidative stress in RPAT and SCAT.

scholarly journals Sphingolipids in High Fat Diet and Obesity-Related Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Songhwa Choi ◽  
Ashley J. Snider
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
De Novo ◽  
Sphingolipid Metabolism ◽  
Bioactive Lipids ◽  
High Fat ◽  
Cardiovascular Tissues ◽  
Systemic Insulin Resistance ◽  
Sphingosine 1 Phosphate ◽  
Traditional Roles

Nutrient oversupply associated with a high fat diet (HFD) significantly alters cellular metabolism, and specifically including sphingolipid metabolism. Sphingolipids are emerging as bioactive lipids that play key roles in regulating functions, in addition to their traditional roles as membrane structure. HFD enhancesde novosphingolipid synthesis and turnover of sphingolipids via the salvage pathway, resulting in the generation of ceramide, and more specifically long chain ceramide species. Additionally, HFD elevates sphingomyelin and sphingosine-1 phosphate (S1P) levels in several tissues including liver, skeletal muscle, adipose tissue, and cardiovascular tissues. HFD-stimulated sphingolipid generation contributes to systemic insulin resistance, dysregulated lipid accumulation, and cytokine expression and secretion from skeletal muscle and adipose tissues, exacerbating obesity-related conditions. Furthermore, altered sphingolipid levels, particularly ceramide and sphingomyelin, are involved in obesity-induced endothelial dysfunction and atherosclerosis. In this review, HFD-mediated sphingolipid metabolism and its impact on HFD-induced biology and pathobiology will be discussed.

scholarly journals Hematologic parameters in coronavirus infection (COVID-19) and their clinical implications

Discoveries ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. e117
Author(s):  
Rao Muhammad Waleed ◽  
◽  
Inbisat Sehar ◽  
Waleed Iftikhar ◽  
Huma Saeed Khan ◽  
...  
Keyword(s):  
Treatment Options ◽  
Clinical Implications ◽  
Cytokine Storm ◽  
Relevant Research ◽  
Coagulation Profile ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Hematologic Profile ◽  
Obscure Origin

Coronaviruses are a class of enveloped RNA viruses that cause infections of the respiratory tract, characterized by fever, tiredness, dry cough, diarrhea, loss of smell or taste, chest pain and shortness of breath. Many patients with mysterious pneumonia were distinguished in December 2019 in Wuhan. The pneumonia of obscure origin was found to be ascribed to a novel coronavirus and described as novel coronavirus pneumonia (NCP). The Chinese authorities initially reported the wave of mysterious pneumonia on December 31st, 2019 and it was declared as an outbreak of international concern on January 30th, 2020. A systematic search of relevant research was conducted, and a total of 58 primary research articles were identified, analyzed, and debated to better understand the hematologic profile in COVID-19 (Coronavirus disease) infection and its clinical implications. All the findings in this article manifest a true impression of the current interpretation of hematological findings of the SARS-COV-2 disease. Pathophysiology of COVID-19 disease can be better interpreted by taking into consideration the hematologic parameters. Clinical implications of the hematologic profile of COVID-19 patients including cytokine storm, coagulation profile, and thrombophilic complications are under-recognized. Therefore, this review focuses on the coagulation profile, cytokine storm, and its treatment options. The role of pre-existing thrombophilia in COVID-19 patients and how it could result in the poor prognosis of the disease is also debated. The recent data suggests that hypercoagulability could be the potential cause of fatalities due to COVID-19. Potential effects of tocilizumab, metronidazole, and ulinastatin in suppressing cytokine storm may help to treat SARS-COV-2 infection. This review also highlights the significance of thrombophilia testing in SARS-CoV-2 patients depending on the clinical features and especially in pregnant women.

Efficacy and safety of oral dapsone in acne vulgaris – experience of a tertiary care teaching hospital in central Lahore

2020 ◽  
Vol 14 (2) ◽  
pp. 87-90
Author(s):  
Sadaf Amin Chaudhry ◽  
Nadia Ali Zafar ◽  
Rabia Hayat ◽  
Ayesha Noreen ◽  
Gulnaz Ali ◽  
...  
Keyword(s):  
Side Effects ◽  
Therapeutic Option ◽  
Acne Vulgaris ◽  
Treatment Options ◽  
Tertiary Care ◽  
Poor Response ◽  
Global Assessment Scale ◽  
Severe Acne ◽  
Hematologic Profile

Background: Acne is the eighth most prevalent disease affecting 9.4% of the population worldwide and its prevalence in our country is estimated to be around 5%. Severe inflammatory acne is most likely to leave scars and in order to prevent facial disfigurement due to acne scarring, early treatment is desirable. Various treatment options have been formulated for acne, and are tailored according to the severity of the disease. Numerous clinical trials have been conducted till now, to determine the usefulness and side effect profile of such therapies, making acne treatment a highly studied area in dermatology. Objective of this study is to highlight the fact that oral Dapsone could be used as a cheaper alternate to isotretinoin in recalcitrant severe acne, especially in females where retinoids are sometimes contraindicated. Patients and methods: 51 patients, suffering from severe nodulocystic acne, fulfilling the criteria, were enrolled from the Department of Dermatology, Sir Ganga Ram Hospital, Lahore. All the study patients were given oral Dapsone 50mg for initial two weeks and then 100mg daily for the next 10 weeks along with oral cimetidine and topical clindamycin application twice daily. Investigator Global Assessment Scale (IGAS) was employed to measure effectiveness. The treatment was considered ʽeffectiveʹ if the patient achieves 2 or more than 2-grade improvement or almost clear or clear skin at the end of 12 weeks according to IGAS scale. The lesion counts were also done before the start of therapy (day 1) and at every two weeks follow up for 12 weeks. The change in lesion count observed between the baseline number and that seen at follow up visits was also used to evaluate the effectiveness of oral Dapsone. Safety was analyzed by fortnightly visits of the patients to look for any undesirable side effects and monitoring of the hematologic profile of the patients. Final follow up was done at the end of 16 weeks. Results: The study was conducted on 51 patients, with a ratio of 1:3 for males and females and a mean age of 25.2 years (SD ±5.81). At 12th week, patients had significant reduction in their acne lesions; with 7 patients (13.7%) showing completely clear skin, 17 patients (33.3%) had almost clear skin, 5 patients (9.8%) had 3-grade improvement. Twelve patients (23.5%) had 2-grade improvement from baseline score and only 2 patients (3.9%) had 1-grade improvement from baseline. Based on percentage reduction of lesions, excellent response was seen in 32 patients (62.7%), good response in 9 patients (17.6%), moderate response in 2 patients (3.9%), while no patient showed poor response. Dapsone was discontinued in 8 patients due to derangement of hematologic profile. Conclusion: Oral Dapsone, when given carefully, is a very effective therapeutic option in severe recalcitrant acne, with limited side effects.

Treatment Options in COVID-19: The Role of Bioavailable Antiviral Ribonucleoside Analog on NHC in vitro

2020 ◽  
Author(s):  
Lara Bittmann
Keyword(s):  
World Health Organization ◽  
Clinical Picture ◽  
Treatment Options ◽  
World Health ◽  
Wuhan City ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

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