TLR4
toll like receptor 4
Gene Context Sentence
Table 2. Analysis of context sentence of TLR4 gene in 24 abstracts.
| PMID | Gene Context Sentence |
|---|---|
| 32249203 | In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. |
| 32295479 | After predicting and evaluating of the third structure of the protein candidate, the best 3 D predicted model was applied for docking studies with Toll-like receptor 4 (TLR4) and HLA-A11:01. […] In the next step, molecular dynamics (MD) simulation was used to evaluate the stability of the designed fusion protein with TLR4 and HLA-A11:01 receptors. […] MD studies demonstrated that the NOM-TLR4 and NOM-HLA-A*11:01 docked models were stable during simulation time. In silico evaluation showed that the designed chimeric protein could simultaneously elicit humoral and cell-mediated immune responses. |
| 32380958 | Disulfide-HMGB1 triggers TLR4 receptors generating pro-inflammatory cytokine release. |
| 32383269 | We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS-CoV-2 to induce inflammatory responses. […] The present study supported the zoonotic origin of SARS-CoV-2 from a bat and also revealed that TLR4 may have a crucial role in the virus-induced inflammatory consequences associated with COVID-19. […] Therefore, selective targeting of TLR4-spike protein interaction by designing competitive TLR4-antagonists could pave a new way to treat COVID-19. |
| 32432519 | We discuss the possible excess risk for COVID-19 infection in the context of the common conditions among shiftworkers, including nurses, doctors, and first responders, among others of high exposure to the contagion, of sleep imbalance and circadian disruption.Abbreviations: ACE2: Angiotensin-converting enzyme 2; APC: Antigen-presenting cells; CCL: Chemokine (C-C motif) ligand; CD+: Adhesion molecule expression; COVID-19: 2019 coronavirus disease; DCs: Dendritic cells; GH: Growth hormone; HPA: Hypothalamic-pituitary-adrenal; HSF: Heat shock factor; HSP70: Heat shock protein 70; HSP90: Heat shock protein 90; IL: Interleukin; INFγ: Interferon-gamma; LT/LB: T/B lymphocytes; MHC: Major histocompatibility complex; NK: Natural killer; RAAS: renin-angiotensin-aldosterone system; SARS: Severe acute respiratory syndrome; SCN: Suprachiasmatic nucleus;SD: Sleep deprivation; SNS: Sympathetic nervous system; Th1/Th2: T helper lymphocytes 1/2; TLR2/TLR4: Toll-like receptor 2/4; TNF-α: Tumor necrosis factor alpha; VEGF: Vascular endothelial growth factor. |
| 32504751 | Such positive outcomes were underlined by a significant inhibitory effect of nifuroxazide on lung and heart contents of toll-like receptor (4) (TLR4)/the inflammasome NALPR3/interleukin- 1β (IL-1β). […] In conclusion: Nifuroxazide attenuates LPS-induced ALI and myocardial injury via interruption of TLR4/NALPR3/IL-1β signaling. |
| 32534337 | This metabolite prevents hepatitis B virus (HBV) replication and influenza A virus (IAV) adsorption and replication through mechanisms involving regulation of oxidative stress and alterations of the TLR4, Akt, MAPK, and NF-κB signalling pathways. |
| 32574273 | Importantly, GL has anti-inflammatory properties by itself via toll like receptor 4 (TLR4) antagonism and therefore compensates for the reduced protection of the downregulated ACE2. |
| 32677533 | Further investigations indicated a strong and stable binding interaction between the vaccine and the toll-like receptor (TLR4). |
| 32731461 | Homology modeling of the construct was done using SWISS-MODEL and then docked with different toll-like-receptors (TLR4, TLR7, and TLR8) using PatchDock, HADDOCK, and FireDock, respectively. […] Docking of C1 with TLR4, TLR7, and TLR8 showed striking interactions with global binding energy of -43.48, -65.88, and -60.24 Kcal/mol, respectively. |
| 32754160 | Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4. |
| 32917282 | Out of 22 eligible articles that investigated candidate genes (2 as associated with COVID-19), the top-ranked genes in the number of studies were ACE2, CLEC4M (L-SIGN), MBL, MxA (n = 3), ACE, CD209, FCER2, OAS-1, TLR4, TNF-α (n = 2). |
| 32984641 | In addition, it is known that lipid A initiates a signaling cascade resulting in activation of various proinflammatory pathways and increases oxidative stress upon binding to tool-like receptor 4 (TLR4). |
| 32988728 | The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. […] We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host’s lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure. |
| 32989935 | Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. […] These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation. |
| 33037393 | Overproduced PAI-1 binds to TLR4 on macrophages, inducing the secretion of proinflammatory cytokines and chemokines. |
| 33039603 | We have tried to search the epitopic component of the S-protein that might be served as crucial targets for the vaccine development and also tried to understand the molecular mechanism of epitopes and TLR4/MD-2 complex for adaptive immunity. […] The study was performed to identify the epitopes, composition of amino acids and its distribution in epitopic regions, composition of amino acid between the identified epitopes, secondary structure architecture of epitopes, physicochemical and biochemical parameters and molecular interaction between the identified epitope and TLR4/MD-2 complex. […] The SARS-CoV-2 can be possibly recognised by TLR4 of host immune cells that are responsible for the adaptive immune response. […] We identified four SARS-CoV-2 S-protein 9mer antigenic epitopes and observed that they bind with the TLR4/MD-2 complex by varied stable molecular bonding interactions. […] Molecular interaction between these characterized epitopes with TLR4/MD-2 complex might be indicated the binding affinity and downstream signalling of adaptive immune response. […] These parameters help to understand the protein-protein interaction between epitopes and TLR4/MD-2 complex. […] The study also revealed different epitopic binding pockets of TLR4/MD-2 complex. |
| 33043110 | The highest binding energy was observed in TLR4 (Toll-like Receptor 4) (-1398.1), and the least is TLR 2 (-1479.6). |
| 33194329 | Molecular docking and dynamics simulation of the chimeric vaccine with the immune receptors (TLR3 and TLR4) predicted efficient binding. |
| 33225084 | Molecular docking was performed to study the interaction of construct with TLR (TLR3, TLR4, and TLR9) molecules. |
| 33345622 | These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). |
| 33349263 | Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. […] The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. |
| 33505220 | TLR4 is an innate immune receptor on the cell surface that recognizes pathogen-associated molecular patterns (PAMPs) including viral proteins and triggers the production of type I interferons and proinflammatory cytokines to combat infection. […] ACE2, the reported entry receptor for SARS-CoV-2, is only present on ~1-2% of the cells in the lungs or has a low pulmonary expression, and recently, the spike protein has been proposed to have the strongest protein-protein interaction with TLR4. […] Here, we review and connect evidence for SARS-CoV-1 and SARS-CoV-2 having direct and indirect binding to TLR4, together with other viral precedents, which when combined shed light on the COVID-19 pathophysiological puzzle. […] We propose a model in which the SARS-CoV-2 spike glycoprotein binds TLR4 and activates TLR4 signalling to increase cell surface expression of ACE2 facilitating entry. […] SARS-CoV-2 also destroys the type II alveolar cells that secrete pulmonary surfactants, which normally decrease the air/tissue surface tension and block TLR4 in the lungs thus promoting ARDS and inflammation. […] Furthermore, SARS-CoV-2-induced myocarditis and multiple-organ injury may be due to TLR4 activation, aberrant TLR4 signalling, and hyperinflammation in COVID-19 patients. […] Therefore, TLR4 contributes significantly to the pathogenesis of SARS-CoV-2, and its overactivation causes a prolonged or excessive innate immune response. […] TLR4 appears to be a promising therapeutic target in COVID-19, and since TLR4 antagonists have been previously trialled in sepsis and in other antiviral contexts, we propose the clinical trial testing of TLR4 antagonists in the treatment of severe COVID-19. […] Also, ongoing clinical trials of pulmonary surfactants in COVID-19 hold promise since they also block TLR4. |
| 33506952 | Different TLRs, like TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 are potentially important in COVID-19 infection. |