scholarly journals COVID-19 impact on liver: inter-organ cross-talk in an acute inflammation

2021 ◽  
Vol 8 (2) ◽  
pp. 38-46
Author(s):  
Dipesh Kumar Yadav ◽  
Alina Singh ◽  
Rajesh Kumar Yadav ◽  
Huang Xing ◽  
Bai Xue Li ◽  
...  
Keyword(s):  
Cross Talk ◽  
Acute Inflammation ◽  
Severe Infection ◽  
Spike Protein ◽  
Underlying Liver Disease ◽  
Angiotensin Converting Enzyme 2 ◽  
Expert Opinions ◽  
Immune Mediated ◽  
Increased Risk ◽  
Cytokine Dysregulation

Since coronavirus disease 2019 (COVID-19) has been a new disease, very less is known about the disease, and guidance for the treatment are often being made on the basis of an experiences or expert opinions. Now it is known that COVID-19 is caused by a new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus which elicit infection to the cells by binding of the spike protein to angiotensin converting enzyme 2 (ACE2). Given the high transmissibility rate of the SARS-Cov-2 virus and known to have cytokine dysregulation by inducing an immune-mediated systemic inflammation, patients with underlying liver disease might be at an increased risk of severe infection and death. Here we report different mechanisms based on the organ cross-talk and other causes that how COVID-19 patients are prone to have liver injury.

scholarly journals Pathology and Anticatalytic Treatment of Exacerbated COVID-19

2022 ◽  
Author(s):  
Jong-hoon Lee ◽  
Seongcheol Cho ◽  
Badar Kanwar ◽  
Keum-ho Lee ◽  
Tuan Ngoc Minh Nguyen ◽  
...  
Keyword(s):  
Spike Protein ◽  
Inflammasome Activation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Genetic Pathway ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Levels ◽  
Neuropilin 1 ◽  
Immune Mediated ◽  
Memory Engram

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated inflammasome diseases. Moreover, its pathophysiology involves the angiotensin-converting enzyme 2 (ACE2) receptor, Toll-like receptor 4 (TLR4) pathway, neuropilin‑1 pathway, inflammasome activation pathway, sterile alpha motif (SAM) and histidine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization pathway, cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway, spike protein/inflammasome-genetic pathway, and immunological memory engram pathway. Therefore, it is necessary to prescribe anticatalytic treatments to alleviate the SARS-CoV-2 inflammasome, immunologic engram, and spike protein levels.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

scholarly journals Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044384
Author(s):  
Guduru Gopal Rao ◽  
Alexander Allen ◽  
Padmasayee Papineni ◽  
Liyang Wang ◽  
Charlotte Anderson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Severe Infection ◽  
Older Age ◽  
Cross Sectional ◽  
North West ◽  
Icu Admission ◽  
Risk Of Death ◽  
Hospitalised Patients ◽  
Increased Risk

ObjectiveThe aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.DesignObservational cohort study.SettingLondon North West Healthcare NHS Trust (LNWH).ParticipantsPatients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measuresDescriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.ResultsThe outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients.ConclusionThe findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

scholarly journals Cell wall N-glycan of Candida albicans ameliorates early hyper- and late hypo-immunoreactivity in sepsis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Masataka Kawakita ◽  
Taiki Oyama ◽  
Ikuma Shirai ◽  
Shuto Tanaka ◽  
Kotaro Akaki ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Severe Infection ◽  
Cytokine Storm ◽  
Immune Exhaustion ◽  
Sepsis Model ◽  
Yeast Strains ◽  
Immune Paralysis ◽  
Tnf Α ◽  
Immunosuppressive Cytokine ◽  
Ifn Γ

AbstractSevere infection often causes a septic cytokine storm followed by immune exhaustion/paralysis. Not surprisingly, many pathogens are equipped with various anti-inflammatory mechanisms. Such mechanisms might be leveraged clinically to control septic cytokine storms. Here we show that N-glycan from pathogenic C. albicans ameliorates mouse sepsis through immunosuppressive cytokine IL-10. In a sepsis model using lipopolysaccharide (LPS), injection of the N-glycan upregulated serum IL-10, and suppressed pro-inflammatory IL-1β, TNF-α and IFN-γ. The N-glycan also improved the survival of mice challenged by LPS. Analyses of structurally defined N-glycans from several yeast strains revealed that the mannose core is key to the upregulation of IL-10. Knocking out the C-type lectin Dectin-2 abrogated the N-glycan-mediated IL-10 augmentation. Furthermore, C. albicans N-glycan ameliorated immune exhaustion/immune paralysis after acute inflammation. Our results suggest a strategy where the immunosuppressive mechanism of one pathogen can be applied to attenuate a severe inflammation/cytokine storm caused by another pathogen.

scholarly journals Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana Prieto-Peña ◽  
Sara Remuzgo-Martínez ◽  
Fernanda Genre ◽  
Verónica Pulito-Cueto ◽  
Belén Atienza-Mateo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Disease Onset ◽  
Immunoglobulin A ◽  
Genetic Network ◽  
Signalling Pathway ◽  
Immune Mediated ◽  
Increased Risk ◽  
Genotype And Allele Frequencies ◽  
Immunoglobulin A Vasculitis

AbstractCytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

scholarly journals Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 57
Author(s):  
Zhi-Ling Zhu ◽  
Xiao-Dan Qiu ◽  
Shuo Wu ◽  
Yi-Tong Liu ◽  
Ting Zhao ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Blocking Effect ◽  
Spike Protein ◽  
Binding Affinities ◽  
The Novel ◽  
Converting Enzyme ◽  
Primary Method ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Effective Drugs

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

scholarly journals The Effects of Aβ1-42 Binding to the SARS-CoV-2 Spike Protein S1 Subunit and Angiotensin-Converting Enzyme 2

2021 ◽  
Vol 22 (15) ◽  
pp. 8226
Author(s):  
John Tsu-An Hsu ◽  
Chih-Feng Tien ◽  
Guann-Yi Yu ◽  
Santai Shen ◽  
Yi-Hsuan Lee ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Viral Entry ◽  
Negative Impact ◽  
Spike Protein ◽  
Infection Model ◽  
Converting Enzyme ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
People With Dementia ◽  
The Impact

Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer’s disease (AD), the major form of dementia, β-amyloid (Aβ) levels in the blood are increased; however, the impact of elevated Aβ levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aβ1-42, but not Aβ1-40, bound to various viral proteins with a preferentially high affinity for the spike protein S1 subunit (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the viral receptor, angiotensin-converting enzyme 2 (ACE2). These bindings were mainly through the C-terminal residues of Aβ1-42. Furthermore, Aβ1-42 strengthened the binding of the S1 of SARS-CoV-2 to ACE2 and increased the viral entry and production of IL-6 in a SARS-CoV-2 pseudovirus infection model. Intriguingly, data from a surrogate mouse model with intravenous inoculation of Aβ1-42 show that the clearance of Aβ1-42 in the blood was dampened in the presence of the extracellular domain of the spike protein trimers of SARS-CoV-2, whose effects can be prevented by a novel anti-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ1-42 to the S1 of SARS-CoV-2 and ACE2 may have a negative impact on the course and severity of SARS-CoV-2 infection. Further investigations are warranted to elucidate the underlying mechanisms and examine whether reducing the level of Aβ1-42 in the blood is beneficial to the fight against COVID-19 and AD.

Anti-obesity Medications in Cancer Therapy: A Comprehensive Insight

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajveer Singh Shekhawat ◽  
Chandi C Mandal
Keyword(s):  
Cross Talk ◽  
Neoplastic Transformation ◽  
Cancer Growth ◽  
Chemotherapeutic Drug ◽  
Essential Step ◽  
Cellular Events ◽  
Oncogenic Pathways ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Potential Use

: The interplay between cancer and obesity is multifactorial and complex with the increased risk of cancer development in obese individuals posing a significant threat. Obesity leads to the upregulation or hyperactivation of several oncogenic pathways in cancer cells, which drives them towards a deleterious phenotype. The cross-talk between cancer and obesity is considered a large contributing factor in the development of chemotherapeutic drug resistance and the resistance to radiotherapy. The link between obesity and the development of cancer is so strong that a medication that demonstrates effectiveness against both conditions would serve as an essential step. In this context, anti-obesity medications provide a worthy list of candidates based on their chemo-preventive potential and chemotherapeutic properties. The current study focuses on exploring the potential of anti-obesity medicines as dual anticancer drugs. These medications target several key signaling pathways (e.g., AMPK, PI3K/Akt/mTOR, MAPK, NF-κB, JNK/ERK), which prove to be crucial for both cancer growth and metastases. Some of these drugs also play an important role in attenuating the signaling and cellular events which incite cancer-obesity cross-talk and demonstrate efficient counteraction of neoplastic transformation. Thus, this review highlights a comprehensive view of the potential use of anti-obesity medicines to treat both cancer and obesity for patients exhibiting both comorbities.

Abstract 16010: Congestive Heart Failure and Coronavirus Disease 2019 Illness Severity

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Max Ruge ◽  
Joanne Michelle D Gomez ◽  
Gatha G Nair ◽  
Setri Fugar ◽  
Jeanne du Fay de Lavallaz ◽  
...  
Keyword(s):  
Heart Failure ◽  
At Risk ◽  
Congestive Heart Failure ◽  
Case Fatality ◽  
Severity Of Illness ◽  
Severe Infection ◽  
Severe Illness ◽  
Increased Risk ◽  
History Of ◽  
Male Sex

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has killed hundreds of thousands worldwide. Those with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. Congestive heart failure (CHF) may lead to worsening COVID-19 symptoms. However, it is unclear if CHF is an independent risk factor for severe COVID-19 infection or if other accompanying comorbidities are responsible for the increased risk. Methods: From March to June 2020, data was obtained from adult patients diagnosed with COVID-19 infection who were admitted in the Rush University System for Health (RUSH) in Illinois. Heart failure patients, determined by ICD code assignments extracted from the electronic medical records, were identified. Multivariable logistic regression was performed between predictor variables and a composite outcome of severe infection consisting of Intensive Care Unit (ICU) admission, intubation, or in-hospital mortality. Results: In this cohort (n=1136), CHF [odds ratio (OR) 1.02] alone did not predict a more severe illness. Prior myocardial infarction [(MI), OR 3.55], history of atrial fibrillation [(AF), OR 2.14], and male sex (OR 1.55) were all significantly (p<0.001) associated with more severe COVID-19 illness course when controlling for CHF (Figure 1). In the 178 CHF patients, more advanced age (68.8 years vs. 63.8 years; p<0.05) and female sex (54.5% vs. 39.1%; p<0.05) were associated with increased severity of illness. Conclusions: Prior MI, history of AF, and male sex predicted more severe COVID-19 illness course in our cohort, but pre-existing heart failure alone did not. However, CHF patients who are females and older in age are at risk for severe infection. These findings help clinicians identify patients with comorbidities early at risk for severe COVID-19 illness.

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