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CMKLR1
Chemokine like receptor 1 also known as ChemR23 (Chemerin Receptor 23) is a protein that in humans is encoded by the ''CMKLR1'' gene. Chemokine receptor-like 1 is a G protein-coupled receptor for the chemoattractant adipokine chemerin and the omega-3 fatty acid eicosapentaenoic acid-derived specialized pro-resolving molecule, resolvin E1 (see Specialized proresolving mediators#EPA-derived resolvins (i.e. RvE)). The murine receptor that shares almost 80% homology with the human receptor, is called Dez. Tissue distribution CMKLR1 shows wide RNA expression profile but is notably high in plasmacytoid dendritic cells, macrophages, cardiomyocytes, adipocytes and endothelial cells. Function Activating CMKLR1 by an agonist mobilizes intracellular calcium and causes the activation of several other signaling cascades like the ERK1 and NF-κB. Initial studies of CMKLR1 suggested that it might have a role in the inflammatory pathways. Its cognate ligand, chemerin was found in joint a ...
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Chemerin
Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein that in humans is encoded by the ''RARRES2'' gene. Function Retinoids exert biologic effects such as potent growth inhibitory and cell differentiation activities and are used in the treatment of hyperproliferative dermatological diseases. These effects are mediated by specific nuclear receptor proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. RARRES1, RARRES2 (this gene), and RARRES3 are genes whose expression is upregulated by the synthetic retinoid tazarotene. RARRES2 is thought to act as a cell surface receptor. Chemerin is a chemoattractant protein that acts as a ligand for the G protein-coupled receptor CMKLR1 (also known as ChemR23). Chemerin is a 14 kDa protein secreted in an inactive form as prochemerin and is activated through cleavage of t ...
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Specialized Proresolving Mediators
Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of lipoxygenase, cyclooxygenase, and cytochrome P450 monooxygenase enzymes. Pre-clinical studies, primarily in animal models and human tissues, implicate SPM in orchestrating the resolution of inflammation. Prominent members include the resolvins and Protectin D1, protectins. SPM join the long list of other physiological agents which tend to limit inflammation (see ) including glucocorticoids, interleukin 10 (an anti-inflammatory cytokine), interleukin 1 receptor antagonist (an inhibitor of the action of pro-inflammatory cytokine, interleukin 1), annexin A1 (an inhibitor of formation of pro-inflammatory metabolites of polyunsaturated fatty acids), and the gaseous resolvins, carbon monoxide (see ), nitric oxide (see ), and hydrogen sulfide (se ...
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Resolvins
Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as docosapentaenoic acid (DPA) and clupanodonic acid. As autacoids similar to hormones acting on local tissues, resolvins are under preliminary research for their involvement in promoting restoration of normal cellular function following the inflammation that occurs after tissue injury. Resolvins belong to a class of polyunsaturated fatty acid (PUFA) metabolites termed specialized proresolving mediators (SPMs). Biochemistry and production Resolvins (Rvs) fall into several sub-classes based on the straight chain PUFA from which they are formed and/or a unique aspect of their structure. The Resolvin Ds (RvDs) are metabolites of the 22-carbon PUFA, DHA (i.e. 4''Z'',7''Z'',10''Z'',13''Z'',16''Z'',19''Z'')-docosahexaenoic acid); the resolvin Es (RvEs) are metabolites of the 20-carbon PUFA, EPA (i.e. 5''Z'',8''Z'',11' ...
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Chemerin Peptides
Chemerin peptides are short peptides (on the order of 9 amino acids) that are produced from the carboxyl terminus of the chemokine chemerin. They display the same activities as chemerin, although at higher efficacy and potency. A particular synthetic chemerin-derived peptide, termed C15, was developed at Oxford University. It showed anti-inflammatory activities. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. C15 was found to promote phagocytosis and efferocytosis in peritoneal macrophages at picomolar concentrations. C15 enhanced macrophage clearance of microbial particles and apoptotic cells by factor of 360% in vitro References See also *Chemerin *CMKLR1 *Chemokine *Efferocytosis In cell biology, efferocytosis (from ''efferre'', Latin fo ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Peritonitis
Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part or the entire abdomen may be tender. Complications may include shock and acute respiratory distress syndrome. Causes include perforation of the intestinal tract, pancreatitis, pelvic inflammatory disease, stomach ulcer, cirrhosis, or a ruptured appendix. Risk factors include ascites (the abnormal build-up of fluid in the abdomen) and peritoneal dialysis. Diagnosis is generally based on examination, blood tests, and medical imaging. Treatment often includes antibiotics, intravenous fluids, pain medication, and surgery. Other measures may include a nasogastric tube or blood transfusion. Without treatment death may occur within a few days. About 20% of people with cirrhosis who are hospitalized have peritonitis. Signs and symptoms Abd ...
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Adipogenesis
Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocytes which lose the potential to differentiate to other types of cells such as chondrocytes, myocytes, and osteoblasts. Terminal differentiation is that preadipocytes differentiate into mature adipocytes. Adipocytes can arise either from preadipocytes resident in adipose tissue, or from bone-marrow derived progenitor cells that migrate to adipose tissue. Introduction Adipocytes play a vital role in energy homeostasis and process the largest energy reserve as triglycerol in the body of animals. Adipocytes stay in a dynamic state, they start expanding when the energy intake is higher than the expenditure and undergo mobilization when the energy expenditure exceeds the intake. This process is highly regulated by counter regulatory hormones t ...
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Insulin Resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar). Insulin is released by the pancreas in response to carbohydrates consumed in the diet. In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. There are many causes of insulin resistance and the underlying process is still not completely understood, but sulfate depletion may be the important factor. Risk factors for insulin resistance include obesity, sedentary lifestyle, family history of diabetes, various health conditions, and certain medications. Insulin resistance is considered a component of the metabolic syndrome. There are multiple ways to measure insulin resistance such as fasting insulin levels or glucose tolerance tests, but these are ...
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Zymosan
Zymosan is a glucan with repeating glucose units connected by β-1,3-glycosidic linkages. It binds to TLR 2 and Dectin-1 (CLEC7A C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the ''CLEC7A'' gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II ...). Zymosan is a ligand found on the surface of fungi, like yeast. Zymosan is prepared from yeast cell wall and consists of protein-carbohydrate complexes. It is used to induce experimental sterile inflammation. In macrophages, zymosan-induced responses include the induction of proinflammatory cytokines, arachidonate mobilization, protein phosphorylation, and inositol phosphate formation. Zymosan A also raises cyclin D2 levels suggesting a role for the latter in macrophage activation besides proliferation. It potentiates acute liver damage after galactosamine injection suggesting that certain types of non ...
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Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ...
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Efferocytosis
In cell biology, efferocytosis (from ''efferre'', Latin for 'to take to the grave', 'to bury') is the process by which apoptotic cells are removed by phagocytic cells. It can be regarded as the 'burying of dead cells'. During efferocytosis, the cell membrane of phagocytic cells engulfs the apoptotic cell, forming a large fluid-filled vesicle containing the dead cell. This ingested vesicle is called an efferosome (in analogy to the term phagosome). This process is similar to macropinocytosis. For apoptosis, the effect of efferocytosis is that dead cells are removed before their membrane integrity is breached and their contents leak into the surrounding tissue. This prevents exposure of tissue to toxic enzymes, oxidants and other intracellular components such as proteases and caspases. Efferocytosis can be performed not only by 'professional' phagocytic cells such as macrophages or dendritic cells, but also by many other cell types including epithelial cells and fibroblasts. To disti ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ...
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