Toll—like receptor

Radix Aconiti Lateralis Preparata (Fuzi) is a traditional Chinese medicine. Its alkaloids are both cardiotonic and cardiotoxic; however, the underlying mechanisms are unclear. Compatibility testing and processing are the primary approaches used to reduce the toxicity of aconite preparations. The purpose of this study was to compare the effects of crude Fuzi (CFZ), CFZ combined with Glycyrrhiza (Gancao) (CFZ+GC), and prepared materials of CFZ (PFZ) on heart failure (HF) in C57BL/6J mice and explore the potential mechanisms of action of CFZ...

The aim of this study was to determine the effects of live probiotics Lactobacillus reuteri (LR) and Clostridium butyricum (CB) on the expression of genes of innate immune system in broiler chick ileum and cecum. Chicks were administered 500 µl water with or without LR or CB, daily from day 1 to 6 after hatching. The ileum and cecum were collected on day 7 for analysis of gene expression of Toll-like receptors (TLRs), pro- and anti-inflammatory cytokines, and antimicrobial peptides (AMPs) using real-time PCR...

Disruption of redox balance due to the overproduction of free radicals and reactive oxygen species (ROS) could cause protein denaturation, lipid peroxidation, and DNA mutation. These lead to an induction of gastrointestinal diseases such as gastric ulcers induced by long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) and ulcerative colitis. Magnetic resonance technique, which is non-invasive and free of radiation exposure, is a promising tool for evaluating redox status in the living body...

The current therapeutic drugs for major depression mainly modulate monoaminergic signaling. Since they are not effective for all patients, the development of novel therapeutic target is required. Recently, it has been reported that inflammation-related molecules are increased in the blood from patients with major depression. Therefore, neuroinflammation is a possible cause of these disorders. However, we still do not know whether neuroinflammation induces depression. Since social and environmental stress is a risk factor for mental illnesses, repeated social defeat stress is employed as an animal model of depression...

BACKGROUND: Substance use disorders and social stress are currently associated with changes in the immune system response by which they induce a proinflammatory state in neurons and glial cells that eventually modulates the reward system. AIMS: The aim of the present work was to assess the role of the immune TLR4 (Toll-like receptors 4) and its signaling response in the increased contextual reinforcing effects of cocaine and reinforcing effects of ethanol (EtOH) induced by social defeat (SD) stress...

The disposal of cacao pod husk, a byproduct of cacao bean processing, can cause serious adverse environmental impacts, motivating scientist to explore and develop potential beneficial applications of this resource. Dried cacao pod husk was extracted with ethanol to obtain a 10.6% pectin of cacao pod husks (pCPH), and its effects on the immunocompetence of Litopenaeus vannamei were estimated. Measured variables included total haemocyte count, differential haemocyte count, phenoloxidase activity, respiratory bursts, as well as phagocytic activity and clearance efficiency against Vibrio alginolyticus after receiving pCPH at 0, 1...

In addition to haemostasis, platelets play an essential role in mechanisms of inflammation and in immunological reactions. Platelets express various toll-like receptors (TLR) on their surface, among them TLR2 and TLR4, which are important for the recognition of bacterial patterns. This study compared TLR2- and TLR4-dependent platelet signalling and their effect on platelet function. Platelet-rich-plasma and washed platelets were prepared from peripheral blood samples of healthy donors. Pam3CSK4 or LPS (lipopolysaccharides from Escherichia coli) were used for stimulation of TLR2 and TLR4...

Cognitive ability plays an important role in mental and physical well-beings in the increasingly ageing populations. Here, based on a sample of 30 cognitive function-discordant monozygotic twin pairs, we aimed to detect specific epigenetic variants potentially related to cognitive function by conducting an epigenome-wide association study (EWAS). Association between methylation level of single CpG site with cognitive function score was tested by linear mixed effect model. Functions of cis-regulatory regions and ontology enrichments were predicted by Genomic Regions Enrichment of Annotations Tool (GREAT)...

BACKGROUND: Intestinal adaptation has been extensively studied experimentally, but very limited data is available on human subjects. In this study we assessed intestinal adaption in humans with short bowel syndrome (SBS). METHODS: We comparatively evaluated mucosal hyperplasia, inflammation, barrier function and nutrient transport using histology, immunohistochemistry and qPCR for selected 52 key genes in duodenal biopsies obtained from children with SBS after weaning off parenteral nutrition (n = 33), and matched controls without intestinal pathology (n = 12)...

AIMS: Cancer pain seriously affects the life quality of patients. Morphine is commonly used for cancer pain, but tolerance development limits its clinical administration. Central immune signaling is important in the development of cancer pain and morphine tolerance. Cannabinoid receptor 2 (CB2) inhibits cancer pain and morphine tolerance by regulating central immune signaling. In the present study, we investigated the mechanisms of central immune signaling involved in morphine tolerance inhibition by the CB2 agonist AM1241 in cancer pain treatment...

BACKGROUND: The macrophage-activating lipopeptide-2 (MALP-2) activates cells carrying a functional Toll-like receptor (TLR)-2/6. Human sebocytes express functional TLR-2, TLR-4 and CD14. Upregulation of stearoyl-CoA desaturase (SCD) and fatty acid desaturase-2 (FADS2) expression induces pro-inflammatory sebaceous activity. On the other hand, corticotropin-releasing hormone (CRH) is likely to serve as an autocrine stress hormone in human sebocytes. In addition to its antiproliferative, lipogenetic and androgen-activating functions, CRH exhibits a pro-inflammatory action and its expression is upregulated in acne-involved sebaceous glands...

Although the innate immune receptor protein, Receptor for Advanced Glycation End products (RAGE), has been extensively studied, there has been renewed interest in RAGE for its potential role in sepsis, along with a host of other inflammatory diseases of chronic, noninfectious origin. In contrast to other innate immune receptors, for example, Toll-like receptors (TLRs), that recognize ligands derived from pathogenic organisms that are collectively known as "pathogen-associated molecular patterns" (PAMPs) or host-derived "damage-associated molecular patterns" (DAMPs), RAGE has been shown to recognize a broad collection of DAMPs exclusively...

Vincristine and bortezomib are effective chemotherapeutics widely used to treat hematological cancers. Vincristine blocks tubulin polymerization, whereas bortezomib is a proteasome inhibitor. Despite different mechanisms of action, the main non-hematological side effect of both is peripheral neuropathy that can last long after treatment has ended and cause permanent disability. Many different cellular and animal models of various aspects of vincristine and bortezomib-induced neuropathies have been generated to investigate underlying molecular mechanisms and serve as platforms to develop new therapeutics...

Niemann-Pick type C1 (NPC1) is a rare neurodegenerative disease. In NPC1 mouse cerebella, the antibacterial enzyme, lysozyme (Lyz2), is significantly increased in multiple cell types. Due to its possible role in toxic fibril deposition, we confirmed Lyz2 overexpression in culture in different control and NPC1 cell types including human NPC1 fibroblasts. Lyz2 expression is induced by Toll-like receptors potentially in response to lipid storage but does not play a functional role in NPC disease pathology.

Psoriasis and psoriatic arthritis are multifactorial chronic disorders whose etiopathogenesis essentially derives from the alteration of several signalling pathways and the co-occurrence of genetic, epigenetic and non-genetic susceptibility factors that altogether affect the functional and structural property of the skin. Although shared and differential susceptibility genes and molecular pathways are known to contribute to the onset of pathological phenotypes, further research is needed to dissect the molecular causes of psoriatic disease and its progression towards Psoriatic Arthritis...

Myeloid-related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest-specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE...

BACKGROUND: CD8+ cells are key players in the identification and elimination of cancer cells. Cancers can escape an effective T cell response by inducing an exhausted cell state, which limits the cytotoxic capacity of the effector cells. Among other mechanisms, new checkpoint inhibitors reactivate exhausted, dysfunctional T cells. CD8+ T cells can eliminate tumor cells after presentation of tumor-specific antigens via antigen-presenting cells (APCs). APC-mediated tumor recognition is mainly stimulated by Toll-like receptors (TLRs)...

More than a quarter of veterans of the 1990-1991 Persian Gulf War suffer from Gulf War Illness (GWI), a chronic, multi-symptom illness that commonly includes musculoskeletal pain. Exposure to a range of toxic chemicals, including sarin nerve agent, are a suspected root cause of GWI. Moreover, such chemical exposures induce a neuroinflammatory response in rodents, which has been linked to several GWI symptoms in rodents and veterans with GWI. To date, a neuroinflammatory basis for pain associated with GWI has not been investigated...

BACKGROUND & AIMS: Chronic colonic inflammation leads to dysplasia and cancer in patients with inflammatory bowel disease. We have described the critical role of innate immune signaling via Toll-like receptor 4 (TLR4) in the pathogenesis of dysplasia and cancer. In the current study, we interrogate the intersection of TLR4 signaling, epithelial redox activity, and the microbiota in colitis-associated neoplasia. METHODS: Inflammatory bowel disease and colorectal cancer data sets were analyzed for expression of TLR4, dual oxidase 2 (DUOX2), and NADPH oxidase 1 (NOX1)...

While bacterial vaginosis (BV) is a well-known type of vaginal dysbiosis, aerobic vaginitis (AV) is an inflammatory condition that remains understudied and under-recognised. It predisposes women to serious complications including urogenital infections and pregnancy problems. Here, we investigated the bacterial community in AV to explore its possible role in AV pathogenesis. We collected vaginal lavage fluid samples of women ( n = 58) classified by wet-mount microscopy as suffering from AV or BV and included an asymptomatic reference group without signs of AV or BV...