A5100347104- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- Antimicrobial Peptides and Activities
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac Ischemia and Reperfusion
- Cell Adhesion Molecules Research
- Mycobacterium research and diagnosis
- Anesthesia and Neurotoxicity Research
- Ferroptosis and cancer prognosis
- Macrophage Migration Inhibitory Factor
- Helicobacter pylori-related gastroenterology studies
- Neonatal and Maternal Infections
- Wound Healing and Treatments
- Hematological disorders and diagnostics
- Cerebrovascular and Carotid Artery Diseases
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- interferon and immune responses
- Proteoglycans and glycosaminoglycans research
- Carbohydrate Chemistry and Synthesis
- Neonatal Respiratory Health Research
- Inflammatory Bowel Disease
- Acute Ischemic Stroke Management
Kunming Medical University
2013-2024
Ningbo Medical Center Lihuili Hospital
2024
Ningbo University
2024
Sun Yat-sen University
2024
Sun Yat-sen Memorial Hospital
2024
The University of Texas Southwestern Medical Center
2012-2022
Ministry of Education of the People's Republic of China
2018
Anhui Medical University
2018
First Bethune Hospital of Jilin University
2017
UNSW Sydney
2016
Abstract Toll-like receptor 4 (TLR4) is present on monocytes and other cell types, mediates inflammatory events such as the release of TNF after exposure to LPS. C3H/HeJ mice are resistant LPS-induced mortality, due a naturally occurring mutation in TLR4. We therefore hypothesized that acute renal failure (ARF) requires systemic triggered by LPS acting extrarenal injected C3H/HeOuJ controls with 0.25 mg LPS, sacrificed them 6 h later for analysis blood urea nitrogen (BUN) kidney tissue (n =...
Significance The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex recognizes lipopolysaccharide (LPS) on Gram-negative bacteria to induce an innate immune response. Neoseptins, chemically synthesized peptidomimetics that bind and activate the mouse TLR4 (mTLR4)/MD-2 independent of LPS, were discovered through unbiased screening reverse genetic studies, improved by chemical modification. NMR X-ray crystallography TLR4/MD-2/Neoseptin-3 determined mechanism which...
Diprovocim is a recently discovered exceptionally potent, synthetic small molecule agonist of TLR2/TLR1 and has shown significant adjuvant activity in anticancer vaccination against murine melanoma. Since bears no structural similarity to the canonical lipopeptide ligands TLR2/TLR1, we investigated how interacts with through vitro biophysical, structural, computational approaches. We found that induced formation heterodimers as well TLR2 homodimers vitro. determined crystal structure complex...
Many endogenous molecules, mostly proteins, purportedly activate the Toll-like receptor 4 (TLR4)-myeloid differentiation factor-2 (MD-2) complex, innate immune for lipopolysaccharide (LPS) derived from gram-negative bacteria. However, there is no structural evidence supporting direct TLR4-MD-2 activation by ligands. Sulfatides (3-O-sulfogalactosylceramides) are natural, abundant sulfated glycolipids that have variously been shown to initiate or suppress inflammatory responses. We show here...
Abstract Endotoxemia‐related acute liver injury has a poor prognosis and high mortality, macrophage polarization plays central role in the pathological process. Pregnane X receptor (PXR) serves as nuclear xenosensor, safeguarding from toxic stimuli. However, effect underlying mechanism of PXR activation on endotoxemic remain largely unknown. Here, expression is reported human murine macrophages, modified immunotypes macrophages. Moreover, significantly attenuated promoted M2 polarization....
Ischemic postconditioning has been demonstrated to be a protective procedure brain damage caused by transient focal ischemia/reperfusion. However, it is elusive whether the protection of against and neuroinflammation via regulating TLR2 TLR4 pathways. In present study, we examined ischemic performed immediately prior recovery cerebral blood supply on various duration ischemia tested hypothesis that its inhibition modulating TLR2/TLR4 Brain in rats was induced using middle artery occlusion...
The pathogenesis of acute renal failure (ARF) occurring during the course sepsis is incompletely understood. Intercellular adhesion molecule-1 (ICAM-1) a key cell molecule upregulated by LPS, which binds to integrins CD11a/CD18 and CD11b/CD18 present on surface leukocytes. We hypothesized that ICAM-1 facilitates injury in LPS-induced ARF. To test this, three groups mice (n = 8 per group) were injected intraperitoneally with 6 mg/kg LPS: 1) normal C57BL/6 mice, 2) targeted deficiency...
In the present study, we tested our hypothesis that atorvastatin exerts its anti-inflammation effect via suppressing LPS-induced rapid upregulation of Toll-like receptor 4 (TLR4) mRNA and downstream p38, ERK, NF-κB signaling pathways in human umbilical-vein endothelial cells (HUVECs) aortic (HAECs). TLR4 expression kinase activities induced by LPS alone or + were quantified using quantitative real-time PCR enzyme-linked immunosorbent assay. Preincubation LPS-stimulated with siRNA was...
A screen conducted with nearly 100000 compounds and a surrogate functional assay for stimulation of an immune response that measured the release TNF-α from treated human THP-1 myeloid cells differentiated along macrophage line led to discovery diprovocims. Unique these efforts special interest, screening leads this new class activators came compound library designed promote cell-surface receptor dimerization. Subsequent comprehensive structure–activity relationship studies improved potency...
Paeoniflorin-6ʹ-O-benzene sulfonate (CP-25) is a modified paeoniflorin, which the main bioactive component of total glucosides peony. This study evaluated anti-inflammatory and immunoregulatory effects CP-25 in mice with collagen-induced arthritis (CIA) potential mechanisms underlying these effects. After onset CIA, were given (17.5, 35, or 70 mg/kg) methotrexate (MTX, 2.0 mg/kg). The index, swollen joint count, spleen histopathology evaluated. T B cell subsets assayed using flow cytometry,...
Acute systemic inflammatory response to severe skin burn injury mediates burn-induced acute lung injury. Ulinastatin is potentially an effective intervention, because it attenuates the induced by endotoxin and improves myocardial function during ischemic shock reperfusion.Rats received full-thickness wounds 30% total body surface area followed delayed resuscitation. The treatment group 50,000 U/kg of ulinastatin was given vehicle only. A sham not burned but otherwise treated identically....
Herein, we report studies leading to the discovery of neoseptins and a comprehensive examination structure-activity relationships (SARs) this new class small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in class, which emerged from screening an α-helix mimetic library, stimulate immune response, act by well-defined mechanism (mouse TLR4 agonist), are easy produce structurally manipulate, exhibit exquisite SARs, nontoxic, elicit improved qualitatively different...
Lipopolysaccharide (LPS) is a major component of the outer wall gram negative bacteria. In high doses LPS contributes to inflammation in sepsis and low grade characteristic metabolic syndrome. We wanted assess role beta2-glycoprotein I (β2GPI) highly conserved plasma protein its different biochemical forms mouse model systemic inflammation. Normal β2GPI deficient mice were administered through their veins assessed for range markers blood liver. Different measured normal given either saline...
Previous studies suggested that central nervous system injury is often accompanied by the activation of Toll-like receptor 4/NF-κB pathway, which leads to upregulation proapoptotic gene expression, causes mitochondrial oxidative stress, and further aggravates inflammatory response induce cell apoptosis. Subsequent have shown NF-κB IκBα can directly act on mitochondria. Therefore, elucidation specific mechanisms in mitochondria may help discover new therapeutic targets for injury. Recent...
Lipopolysaccharides from Gram-negative bacteria interact with the mammalian immune system to trigger a cascade of physiological events leading shock syndrome which results in death over 70% cases severe shock. It is known that supramolecular structures lipopolysaccharide aggregates are critical contributors their biological activities. Despite this, molecular basis for formation regular hexagonal plates and arrays observed films suspensions unknown. Since these two dimensional, it unlikely...
To test the hypothesis that combinatorial interference of toll-like receptor 2 (TLR2) and TLR4 is superior to isolated TLR2 or in stabilizing atherosclerotic plaques, lentiviruses carrying small interfering RNA were constructed proved efficacious for knocking down mRNA protein expression significantly vitro. One hundred fifty apolipoprotein E−/− mice fed a high-fat diet divided into control, mock, TLR2i, TLR4i + 4i subgroups constrictive collar was placed around carotid artery these induce...
The diprovocims, a new class of toll-like receptor (TLR) agonists, bear no similarity to prior TLR act through well-defined mechanism (TLR1/TLR2 agonist), exhibit exquisite structure–activity relationships, and display in vivo adjuvant activity. They possess potent efficacious agonist activity toward human TLR1/TLR2 but modest agonism the murine receptor. A manner by which diprovocims can be functionalized without impacting hTLR1/TLR2 is detailed, permitting future linkage antigenic,...
Previously, we showed that an oligodeoxynucleotide (ODN) with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, its underlying mechanisms remain to be elucidated. Upon bioinformatic analysis revealing sequence ODN is consensus interferon regulatory factor 5 (IRF5) binding site cis-regulatory elements proinflammatory cytokines, tried explore whether could...
The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion participants who had MRI evidence acute ischemia at different clinical probabilities ischemic attack (TIA) stroke.Cohort from emergency and outpatient settings. Clinicians levels training gave each participant a diagnostic probability (probable when TIA/stroke was most likely differential diagnosis; possible not uncertain could be...
Protein phosphatase 1 (PP1) inhibitors play a role in tumor progression through different mechanisms. regulatory subunit 14D (PPP1R14D) is an inhibitor of PP1. However, the PPP1R14D tumors and its mechanism action are largely unknown. The purpose present study was to investigate expression, function lung adenocarcinoma (LUAD). In study, GEPIA database analysis immunohistochemistry demonstrated that highly expressed LUAD tissues expression negatively correlated with age patients positively...