Neuropilins: C-end rule peptides and their association with nociception and COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Jobe A
PROVIDER: S-EPMC7997051 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThe COVID-19 pandemic is a significant public health crisis that is hitting hard on people's health, well-being, and freedom of movement, and affecting the global economy. Scientists worldwide are competing to develop therapeutics and vaccines; currently, three drugs and two vaccine candidates have been given emergency authorization use. However, there are still questions of efficacy with regard to specific subgroups of patients and the vaccine's scalability to the general public. Under such circumstances, understanding COVID-19 symptoms is vital in initial triage; it is crucial to distinguish the severity of cases for effective management and treatment. This study aimed to discover symptom patterns and overall symptom rules, including rules disaggregated by age, sex, chronic condition, and mortality status, among COVID-19 patients.MethodsThis study was a retrospective analysis of COVID-19 patient data made available online by the Wolfram Data Repository through May 27, 2020. We applied a widely used rule-based machine learning technique called association rule mining to identify frequent symptoms and define patterns in the rules discovered.ResultIn total, 1,560 patients with COVID-19 were included in the study, with a median age of 52 years. The most frequently occurring symptom was fever (67%), followed by cough (37%), malaise/body soreness (11%), pneumonia (11%), and sore throat (8%). Myocardial infarction, heart failure, and renal disease were present in less than 1% of patients. The top ten significant symptom rules (out of 71 generated) showed cough, septic shock, and respiratory distress syndrome as frequent consequents. If a patient had a breathing problem and sputum production, then, there was higher confidence of that patient having a cough; if cardiac disease, renal disease, or pneumonia was present, then there was a higher confidence of septic shock or respiratory distress syndrome. Symptom rules differed between younger and older patients and between male and female patients. Patients who had chronic conditions or died of COVID-19 had more severe symptom rules than those patients who did not have chronic conditions or survived of COVID-19. Concerning chronic condition rules among 147 patients, if a patient had diabetes, prerenal azotemia, and coronary bypass surgery, there was a certainty of hypertension.ConclusionThe most frequently reported symptoms in patients with COVID-19 were fever, cough, pneumonia, and sore throat; while 1% had severe symptoms, such as septic shock, respiratory distress syndrome, and respiratory failure. Symptom rules differed by age and sex. Patients with chronic disease and patients who died of COVID-19 had severe symptom rules more specifically, cardiovascular-related symptoms accompanied by pneumonia, fever, and cough as consequents.
| S-EPMC7966840 | biostudies-literature
Project description:Screening of phage libraries expressing random peptides for binding to prostate cancer cells primarily yielded peptides that had a C-terminal arginine (or rarely lysine) residue, usually in a consensus context R/KXXR/K. Phage expressing these sequences and synthetic nanoparticles coated with them bound to and were internalized into cells. The C-terminal arginine (or lysine) was essential to the activity; adding another amino acid, or even blocking the free carboxyl group of this arginine residue by amidation, eliminated the binding and internalizing activity. An internal R/KXXR/K can be exposed and switched on by a cleavage by a protease. The strict requirement for C-terminal exposure of the motif prompted us to term the phenomenon the C-end rule (CendR). Affinity chromatography showed that the CendR peptides bind to neuropilin-1 (NRP-1) on the target cells. NRP-1 is a cell-surface receptor that plays an essential role in angiogenesis, regulation of vascular permeability, and the development of the nervous system. VEGF-A165 and other ligands of NRP-1 possess a C-terminal CendR sequence that interacts with the b1 domain of NRP-1 and causes cellular internalization and vascular leakage. Our CendR peptides have similar effects, particularly when made multivalent through coupling to a particle. We also noted a unique and important activity of these peptides: penetration and transportation through tissues. The peptides were able to take payloads up to the nanoparticle size scale deep into extravascular tissue. Our observations have implications in drug delivery and penetration of tissue barriers and tumors.
| S-EPMC2752543 | biostudies-literature
Project description:BackgroundHuman behavior is crucial in health outcomes. Particularly, individual behavior is a determinant of the success of measures to overcome critical conditions, such as a pandemic. In addition to intrinsic public health challenges associated with COVID-19, in many countries, some individuals decided not to get vaccinated, streets were crowded, parties were happening, and businesses struggling to survive were partially open, despite lockdown or stay-at-home instructions. These behaviors contrast with the instructions for potential benefits associated with social distancing, use of masks, and vaccination to manage collective and individual risks.ObjectiveConsidering that human behavior is a result of individuals' social and economic conditions, we investigated the social and working characteristics associated with reports of appropriate protective behavior in Brazil.MethodsWe analyzed data from a large web survey of individuals reporting their behavior during the pandemic. We selected 3 common self-care measures: use of protective masks, distancing by at least 1 m when out of the house, and handwashing or use of alcohol, combined with assessment of the social context of respondents. We measured the frequency of the use of these self-protective measures. Using a frequent pattern-mining perspective, we generated association rules from a set of answers to questions that co-occur with at least a given frequency, identifying the pattern of characteristics of the groups divided according to protective behavior reports.ResultsThe rationale was to identify a pool of working and social characteristics that might have better adhesion to behaviors and self-care measures, showing these are more socially determined than previously thought. We identified common patterns of socioeconomic and working determinants of compliance with protective self-care measures. Data mining showed that social determinants might be important to shape behavior in different stages of the pandemic.ConclusionsIdentification of context determinants might be helpful to identify unexpected facilitators and constraints to fully follow public policies. The context of diseases contributes to psychological and physical health outcomes, and context understanding might change the approach to a disease. Hidden social determinants might change protective behavior, and social determinants of protective behavior related to COVID-19 are related to work and economic conditions.Trial registrationNot applicable.
| S-EPMC9202654 | biostudies-literature
Project description:Although most SARS-CoV-2-infected individuals experience mild COVID-19, some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly upregulation of the TNF/IL-1beta-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1beta-driven inflammation, and this was not seen in patients with milder COVID-19 infection. Based on this, we propose that the type I IFN response exacerbates inflammation in patients with severe COVID-19 infection.
2020-07-06 | GSE149689 | GEO
Project description:Neuropilin-1 (NRP-1) is a hub receptor that plays an essential role in angiogenesis and vascular permeability. It is over-expressed in the new blood vessels grown by tumor cells and is a target for anti-tumor treatments. Peptides that expose the consensus sequence R/K/XXR/K at the C-terminus (C-end rule or CendR peptides) bind to NRP-1 and are internalized into the cell. We used peptide phage display binding assays and molecular dynamics (MD) simulations to study the potential role of the central residues of CendR peptides in binding and activation of the NRP-1 receptor. The high stability of RPAR-receptor domain complex stems from the formation of a characteristic pattern of three hydrogen bonds between the peptide C-terminus and the residues in the NRP-1 loop III. Any changes in the peptide structure that fail to preserve this triad result in a less-stable complex. We performed a systematic study of RXXR mutants, where X=A/D/S/R/P, in order to test the effect of replacement of A or P on the binding capabilities. Our results, both experimental and computational, show that RRAR, RDAR, RPDR, RPRR and RPPR are capable of binding NRP-1. However, only RPPR and RPRR segments form an optimal organization around loop III with low potential energy. In other analogs, the absence of these stabilizing interactions always results in higher potential energy of the complexes. The binding of RPAR analogs does not guarantee receptor activation; only stable complexes that are properly stabilized via loop III appear able to trigger NRP-1 activation.
| S-EPMC6146283 | biostudies-literature
Project description: Not available
| S-BSST563 | biostudies-other
Project description:Lung biopsies were collected from recently deceased patients, who tested positive and were treated for SARS-CoV-2 infections, or from patients that succumbed to a non-inflammatory unrelated disease, serving as control. Two samples were taken from each patient either from macroscopically affected lung tissue, for SARS-CoV-2 patients, or healthy homogeneous lung parenchyma of the control patients. All samples were then subjected to shotgun proteomics analysis using data independent acquisition approach.
2023-03-08 | PXD030009 | Pride
Project description:Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behavior. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome- wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities.
2021-04-15 | GSE168739 | GEO
Project description:The N-end rule pathway is a proteolytic system in which N-terminal residues of short-lived proteins are recognized by recognition components (N-recognins) as essential components of degrons, called N-degrons. Known N-recognins in eukaryotes mediate protein ubiquitylation and selective proteolysis by the 26S proteasome. Substrates of N-recognins can be generated when normally embedded destabilizing residues are exposed at the N terminus by proteolytic cleavage. N-degrons can also be generated through modifications of posttranslationally exposed pro-N-degrons of otherwise stable proteins; such modifications include oxidation, arginylation, leucylation, phenylalanylation, and acetylation. Although there are variations in components, degrons, and hierarchical structures, the proteolytic systems based on generation and recognition of N-degrons have been observed in all eukaryotes and prokaryotes examined thus far. The N-end rule pathway regulates homeostasis of various physiological processes, in part, through interaction with small molecules. Here, we review the biochemical mechanisms, structures, physiological functions, and small-molecule-mediated regulation of the N-end rule pathway.
| S-EPMC3610525 | biostudies-literature
