Project description:Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.
Project description:The coronavirus disease 2019 (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global ongoing pandemic. Timely, accurate and non-invasive SARS-CoV-2 detection in both symptomatic and asymptomatic patients, as well as determination of their immune status, will facilitate effective large-scale pandemic control measures to prevent the spread of COVID-19. Saliva is a biofluid whose anatomical source and location is of particularly strategic relevance to COVID-19 transmission and monitoring. This review focuses on the role of saliva as both a foe (a common mode of viral transmission via salivary droplets and potentially aerosols) and a friend (as a non-invasive diagnostic tool for viral detection and immune status surveillance) in combating COVID-19.
Project description:BackgroundA higher chemotherapy completion rate is associated with better outcomes including treatment efficacy and overall survival. Exercise may have the potential to improve relative dose intensity (RDI) by reducing the frequency and severity of chemotherapy-related toxicities. We examined the association between exercise adherence and RDI and possible clinical- and health-related fitness predictors of RDI.MethodsChemotherapy records were extracted from the electronic medical record for patients enrolled in the ENACT trial (n = 105). Chemotherapy completion was assessed using average RDI. A threshold of 85% was established for "high" versus "low" RDI. Logistic regression analyses were used to estimate the associations between the clinical- and health-related fitness predictors of RDI.ResultsPatients with breast cancer (BC) had a significantly higher average RDI (89.8% ± 17.6%) compared with gastrointestinal cancer (GI) (76.8% ± 20.9%, p = 0.004) and pancreatic cancer (PC) (65.2% ± 20.1%, p < 0.001). Only 25% of BC patents required a dose reduction compared to 56.3% of GI and 86.4% of PC patients. Cancer site was significantly associated with RDI. Compared with BC, patients with GI (β = -0.12, p = 0.03) and PC (β = -0.22, p = 0.006) achieved significantly lower RDI. Every 2.72 unit increase in overall exercise adherence led to a significant 7% decrease in RDI (p = 0.001) in GI patients. Metastatic GI patients had a 15% RDI increase for every 2.72 unit increase in exercise adherence (p = 0.04).ConclusionExercise is a supportive therapy that has potential to enhance chemotherapy tolerance and completion. The relationship between exercise adherence and RDI is influenced by factor such as cancer site and treatment type. Special attention must be paid to how exercise is prescribed to ensure that exercise adherence does not negatively affect RDI. Cancer site, exercise dosage, and multimodal interventions to address toxicities are key areas identified for future research.
Project description:Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in more than 6 million deaths worldwide. COVID-19 is a respiratory disease characterized by pulmonary dysfunction leading to acute respiratory distress syndrome (ARDs), as well as disseminated coagulation, and multi-organ dysfunction. Neutrophils and neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of COVID-19. In this review, we highlight key gaps in knowledge, discuss the heterogeneity of neutrophils during the evolution of the disease, how they can contribute to COVID-19 pathogenesis, and potential therapeutic strategies that target neutrophil-mediated inflammatory responses.
Project description:The aim of the present manuscript is to discuss on potential pros and cons of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as glucose-lowering agents during COVID-19 pandemic, and what is more to evaluate them as potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without diabetes mellitus type 2. Besides being important glucose-lowering agents, GLP-1RAs pose promising anti-inflammatory and anti-obesogenic properties, pulmonary protective effects, as well as beneficial impact on gut microbiome composition. Hence, taking everything previously mentioned into consideration, GLP-1RAs seem to be potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without type 2 diabetes mellitus, as well as excellent antidiabetic (glucose-lowering) agents during COVID-19 pandemic times.
Project description:Tumor necrosis factor-alpha (TNFα) can bind two distinct receptors (TNFR1/2). The transmembrane form (tmTNFα) preferentially binds to TNFR2. Upon tmTNFα cleavage by the TNF-alpha-converting enzyme (TACE), its soluble (sTNFα) form is released with higher affinity for TNFR1. This assortment empowers TNFα with a plethora of opposing roles in the processes of tumor cell survival (and apoptosis) and anti-tumor immune stimulation (and suppression), in addition to angiogenesis and metastases. Its functions and biomarker potential to predict cancer progression and response to immunotherapy are reviewed here, with a focus on lung cancer. By mining existing sequencing data, we further demonstrate that the expression levels of TNF and TACE are significantly decreased in lung adenocarcinoma patients, while the TNFR1/TNFR2 balance are increased. We conclude that the biomarker potential of TNFα alone will most likely not provide conclusive findings, but that TACE could have a key role along with the delicate balance of sTNFα/tmTNFα as well as TNFR1/TNFR2, hence stressing the importance of more research into the potential of rationalized treatments that combine TNFα pathway modulators with immunotherapy for lung cancer patients.
Project description:In order to efficiently replicate, viruses require precise interactions with host components and often hijack the host cellular machinery for their own benefit. Several mechanisms involved in protein synthesis and processing are strongly affected and manipulated by viral infections. A better understanding of the interplay between viruses and their host-cell machinery will likely contribute to the development of novel antiviral strategies. Here, we discuss the current knowledge on the interactions between influenza A virus (IAV), the causative agent for most of the annual respiratory epidemics in humans, and the host cellular proteostasis machinery during infection. We focus on the manipulative capacity of this virus to usurp the cellular protein processing mechanisms and further review the protein quality control mechanisms in the cytosol and in the endoplasmic reticulum that are affected by this virus.