A5011522727- Neuropeptides and Animal Physiology
- Regulation of Appetite and Obesity
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Response and Inflammation
- Receptor Mechanisms and Signaling
- Erythrocyte Function and Pathophysiology
- Biochemical Analysis and Sensing Techniques
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Intracerebral and Subarachnoid Hemorrhage Research
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- MicroRNA in disease regulation
- Thermal Regulation in Medicine
- Cell Adhesion Molecules Research
- Biochemical effects in animals
- Dietary Effects on Health
- Adipose Tissue and Metabolism
- Histone Deacetylase Inhibitors Research
The First People's Hospital of Xiaoshan District, Hangzhou
2013-2024
University of Alberta
2015-2022
Merck & Co., Inc., Rahway, NJ, USA (United States)
2020-2021
Tang Hospital
2018
Southeast University
2017
Cancer Institute (WIA)
1995-2016
Shanghai Sixth People's Hospital
2015-2016
Shanghai Jiao Tong University
2015
San Francisco General Hospital
2015
University of California, San Francisco
2015
Our study has shown that plasma levels of ghrelin, a stomach-derived peptide, are significantly reduced in sepsis, and ghrelin administration improves organ blood flow via nuclear factor (NF)-kappaB-dependent pathway. However, it remains unknown whether any protective effects on severe sepsis-induced acute lung injury (ALI) and, if so, inhibition NF-kappaB plays role it.To test the hypothesis reduces ALI mortality through NF-kappaB.Sepsis was induced rats by cecal ligation puncture (CLP)....
To test the hypothesis that administration of ghrelin attenuates inflammatory responses in sepsis through vagal nerve stimulation.Ghrelin has been demonstrated to possess multiple functions, including stimulation vagus nerve. Our recent study shown plasma levels were significantly reduced sepsis; and improved organ perfusion function. However, it remained unknown whether also decreases proinflammatory cytokines and, if so, down-regulatory effect is mediated by activation nerve.Male rats...
Although phytochemical curcumin has been shown to possess anti-inflammatory properties, it remains unknown whether this agent any beneficial effects in sepsis. The purpose of study was demonstrate protects septic animals and, if so, activation peroxisome proliferator-activated receptor (PPAR)-gamma, an nuclear receptor, plays role.Prospective, controlled, and randomized animal study.A research institute laboratory.Male Sprague-Dawley rats.A bolus injection 0.2 micromol given intravenously...
Abstract Lung fibrosis, or the scarring of lung, is a devastating disease with huge unmet medical need. There are limited treatment options and its prognosis worse than most types cancer. We previously discovered that MK-0429 an equipotent pan-inhibitor αv integrins reduces proteinuria kidney fibrosis in preclinical model. In present study, we further demonstrated significantly inhibits progression bleomycin-induced lung injury search newer integrin inhibitors for characterized monoclonal...
Amorphous CaCO3 (ACC) is stabilized by the presence of phytic acid, a natural inositol hexakisphosphate (IP6). Micrometer-sized hollow spheres ACC have been obtained (see Figure). The are stable for at least three months in solution, which equivalent to that described more complex special biopolymers biomineralization processes, and far exceeds previously known stability prepared synthetic molecules. Supporting information this article available on WWW under...
Milk fat globule epidermal growth factor 8 (MFG-E8) is a potent opsonin for the clearance of apoptotic cells and produced by mononuclear immune competent organs including spleen lungs. It attenuates chronic acute inflammation such as autoimmune glomerulonephritis bacterial sepsis enhancing cell clearance. Ischemia-reperfusion (I/R) injury gut results in severe inflammation, apoptosis, remote organ damage, lung (ALI).To determine whether MFG-E8 intestinal pulmonary after I/R.Wild-type (WT)...
Clearance of apoptotic cells is crucial to maintain cellular function under normal and pathological conditions. We have recently shown that administration immature dendritic cell-derived exosomes septic animals promotes phagocytosis improves survival by providing milk fat globule epidermal growth factor-factor VIII (MFG-E8). MFG-E8 acts as an opsonin for be engulfed phagocytosis. In the present study we investigated whether CX3C-chemokine fractalkine (CX3CL1) cell clearance through induction...
Sepsis, a highly lethal systemic inflammatory syndrome, is associated with increases of proinflammatory cytokines (e.g., TNF-alpha, HMGB1) and the accumulation apoptotic cells that have potential to be detrimental. Depending on timing tissue, prevention apoptosis in sepsis beneficial; however, thwarting development secondary necrosis through active removal by phagocytosis may offer novel anti-sepsis therapy. Immature dendritic (IDCs) release exosomes contain milk fat globule EGF factor VIII...
Compared to normal tissues, many cancer cells overexpress autotaxin (ATX). This secreted enzyme produces extracellular lysophosphatidate, which signals through 6 GPCRs drive progression. Our previous work showed that ATX inhibition decreases 4T1 breast tumor growth in BALB/c mice by 60% for about 11 d. However, do not produce significant ATX. Instead, the is produced adjacent mammary adipose tissue. We investigated molecular basis of this interaction human and mouse tumors. Inflammatory...
Milk fat globule-epidermal growth factor 8 (MFG-E8) regulates innate immune function by modulating cellular signaling, which is less understood. Herein, we aimed to investigate the direct anti-inflammatory role of MFG-E8 in macrophages pre-treatment with recombinant murine (rmMFG-E8) followed stimulation LPS RAW264.7 cells and peritoneal macrophages, isolated from wild-type (WT) or MFG-E8−/− mice. mouse treated rmMFG-E8 significantly downregulated LPS-induced TNF-α mRNA 25% 24%, protein...
In sepsis, several cell types (e.g., lymphocytes) undergo apoptosis and have the potential to harm host if not cleared by professional phagocytes. Apoptotic cells display "eat me" signals such as phosphatidylserine that can be readily recognized For full engulfment of these cells, binding integrin alpha(v)beta(3), mediated bridging protein, milk fat globule epidermal growth factor-factor VIII (MFG-E8), is necessary. We hypothesized that, in phagocytosis apoptotic impaired due decreased...
Our previous studies have shown that norepinephrine (NE) upregulates proinflammatory cytokines by activating alpha(2)-adrenoceptor. Therefore, modulation of the sympathetic nervous system represents a novel treatment for sepsis. We also stomach-derived peptide, ghrelin, is downregulated in sepsis and its intravenous administration decreases mitigates organ injury. However, it remains unknown whether ghrelin inhibits activity through central receptors [i.e., growth hormone secretagogue...
Gut ischemia/reperfusion (I/R) injury is a serious condition in intensive care patients. Activation of immune cells adjacent to the huge endothelial cell surface area intestinal microvasculature produces initially local and then systemic inflammatory responses. Stimulation vagus nerve can rapidly attenuate responses through inhibiting activation macrophages cells. Ghrelin, novel orexigenic hormone, produced predominately gastrointestinal system. Ghrelin receptors are expressed at high...
Background Norepinephrine (NE) modulates the responsiveness of macrophages to proinflammatory stimuli through activation adrenergic receptors (ARs). Being part stress response, early increases NE in sepsis sustain adverse systemic inflammatory responses. The intestine is an important source release stage cecal ligation and puncture (CLP)-induced rats, which then stimulates TNF-α production Kupffer cells (KCs) α2-AR. It know three α2-AR subtypes (i.e., α2A, α2B or α2C) responsible for...
Objectives: We have recently shown that ghrelin, a novel orexigenic hormone, is reduced in sepsis. Ghrelin treatment, mediated through ghrelin receptors the brain, attenuates sepsis-induced inflammation and mortality. Gut barrier dysfunction common High-mobility group B1 (HMGB1) increases gut permeability both vitro vivo. However, it remains unknown whether has any effects on HMGB1 function hypothesized decreases release central receptors. Design: Prospective, controlled, randomized animal...
Endogenous molecules released by dying cells [i.e., damage-associated molecular patterns (DAMPs)] after trauma and severe blood loss can activate pattern recognition receptors, leading to a cascade of inflammatory responses organ injury. Mitochondrial transcription factor A (TFAM) is for mitochondrial DNA. TFAM structurally related high mobility group box 1 (HMGB1), an important member DAMPs. We, therefore, hypothesized that be into the circulation hemorrhage initiate responses. In order...
Myristoylation, the N-terminal modification of proteins with fatty acid myristate, is critical for membrane targeting and cell signaling. Because cancer cells often have increased N-myristoyltransferase (NMT) expression, NMTs were proposed as anti-cancer targets. To systematically investigate this, we performed robotic line screens discovered a marked sensitivity hematological lines, including B-cell lymphomas, to potent pan-NMT inhibitor PCLX-001. PCLX-001 treatment impacts global...
The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is anti-inflammatory in a cell-based system and animal models of endotoxemia. We have shown that PPAR-gamma gene expression downregulated macrophages after lipopolysaccharide (LPS) stimulation. However, it remains unknown whether hepatic altered sepsis and, if so, LPS directly downregulates PPAR-gamma. To study this, rats were subjected to by cecal ligation puncture (CLP). Hepatic tissues harvested at 5, 10,...
Abstract Sepsis is a critical inflammatory condition from which numerous patients die due to multiple organ failure and septic shock. The vasoactive hormone adrenomedullin (AM) its binding protein (AMBP-1) are beneficial in sepsis by abrogating the progression irreversible shock decreasing proinflammatory cytokine release. To investigate anti-inflammatory mechanism, we studied determine effect of AM/AMBP-1 complex on peroxisome proliferator-activated receptor-γ (PPAR-γ) expression activation...
In the terrorist radiation exposure scenario, victims are likely to suffer from additional injuries such as sepsis. Our previous studies have shown that ghrelin is protective in However, it remains unknown whether ameliorates sepsis-induced organ injury and mortality after exposure. The purpose of this study determine human attenuates improves survival a rat model combined (RCI) and, if so, potential mechanism responsible for benefit. To this, adult male rats were exposed 5-Gy whole body...
To determine whether administration of a vasoactive peptide, human adrenomedullin (AM), in combination with its binding protein (ie, AMBP-1), prevents or minimizes hepatic ischemia-reperfusion (I/R) injury.Hepatic I/R injury results from tissue hypoxia and subsequent inflammatory responses. Even though numerous pharmacological modalities substances have been studied to reduce I/R-induced mortality, none entirely successful. We shown that AM/AMBP-1 produces significant beneficial effects...
Prevention of lymphocyte apoptosis by caspase inhibition has been proposed as a novel treatment approach in sepsis. However, it not clearly demonstrated that inhibitors improve survival sepsis models when dosed post-insult. Also, there are concerns might suppress the immune response. Here we characterize VX-166, broad inhibitor, potential for sepsis.VX-166 was studied number enzymatic and cellular assays. The compound then tested murine model endotoxic shock (lipopolysaccharide (LPS), 20...