scholarly journals Liver-Derived Exosomes and Their Implications in Liver Pathobiology

2018 ◽  
Vol 19 (12) ◽  
pp. 3715 ◽  
Author(s):  
Sumi Sung ◽  
Jieun Kim ◽  
Youngmi Jung
Keyword(s):  
Liver Diseases ◽  
The Body ◽  
Target Cells ◽  
Liver Sinusoidal Endothelial Cells ◽  
Nonparenchymal Cells ◽  
Hepatic Cells ◽  
Donor Cells ◽  
Wide Range ◽  
Potential Applications ◽  
Health And Disease

The liver has a wide range of physiological functions in the body, and its health is maintained by complex cross-talk among hepatic cells, including parenchymal hepatocytes and nonparenchymal cells. Exosomes, which are one method of cellular communication, are endosomal-derived small vesicles that are released by donor cells and delivered to the target cells at both short and long distances. Because exosomes carry a variety of cargoes, including proteins, mRNAs, microRNAs and other noncoding RNAs originating from donor cells, exosomes convey cellular information that enables them to potentially serve as biomarkers and therapeutics in liver diseases. Hepatocytes release exosomes to neighboring hepatocytes or nonparenchymal cells to regulate liver regeneration and repair. Nonparenchymal cells, including hepatic stellate cells, liver sinusoidal endothelial cells, and cholangiocytes, also secrete exosomes to regulate liver remodeling upon liver injury. Exosomes that are released from liver cancer cells create a favorable microenvironment for cancer growth and progression. In this review, we summarize and discuss the current findings and understanding of exosome-mediated intercellular communication in the liver, with a particular focus on the function of exosomes in both health and disease. Based on the current findings, we suggest the potential applications of exosomes as biomarkers and therapeutics for liver diseases.

scholarly journals Intercellular Communication between Hepatic Cells in Liver Diseases

2019 ◽  
Vol 20 (9) ◽  
pp. 2180 ◽  
Author(s):  
Keisaku Sato ◽  
Lindsey Kennedy ◽  
Suthat Liangpunsakul ◽  
Praveen Kusumanchi ◽  
Zhihong Yang ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Therapeutic Target ◽  
Liver Diseases ◽  
Cell Communication ◽  
Liver Cells ◽  
Small Particles ◽  
Hepatic Cells ◽  
Donor Cells ◽  
Parenchymal Cells ◽  
Novel Therapeutic

Liver diseases are perpetuated by the orchestration of hepatocytes and other hepatic non-parenchymal cells. These cells communicate and regulate with each other by secreting mediators such as peptides, hormones, and cytokines. Extracellular vesicles (EVs), small particles secreted from cells, contain proteins, DNAs, and RNAs as cargos. EVs have attracted recent research interests since they can communicate information from donor cells to recipient cells thereby regulating physiological events via delivering of specific cargo mediators. Previous studies have demonstrated that liver cells secrete elevated numbers of EVs during diseased conditions, and those EVs are internalized into other liver cells inducing disease-related reactions such as inflammation, angiogenesis, and fibrogenesis. Reactions in recipient cells are caused by proteins and RNAs carried in disease-derived EVs. This review summarizes cell-to-cell communication especially via EVs in the pathogenesis of liver diseases and their potential as a novel therapeutic target.

Magnesium Incorporated Polycaprolactone-Based Composite Nanofibers

2015 ◽  
Author(s):  
Nava P. Rijal ◽  
Udhab Adhikari ◽  
Narayan Bhattarai
Keyword(s):  
Composite Nanofibers ◽  
Testing Machine ◽  
The Body ◽  
Electrospinning Technique ◽  
Adhesion Properties ◽  
Wide Range ◽  
Low Molecular Weight Chitosan ◽  
Healing Tissue ◽  
Potential Applications ◽  
Implant Coatings

Recent advances in developing composite nanofibers are of great interest for scientific community due to their wide range of potential applications in biomedical engineering such as drug delivery, wound healing, tissue engineering and implant coatings. Here, we present a fabrication of Mg incorporated polycaprolactone/low molecular weight chitosan (PCL/LMW-CS) composite nanofiber via an electrospinning technique. PCL, a synthetic polymer, has good mechanical properties, whereas, chitosan, a natural polymer, has good bio-functional properties and good cell adhesion properties. Furthermore, magnesium is the second most abundant intracellular cation in the body and is important to metabolism. These nanofibers were characterized by using Scanning Electron Microscopy (SEM), ImageJ, and Instron Universal Testing Machine.

scholarly journals Glucocorticoid Receptor in Health and Disease

2009 ◽  
Vol 28 (4) ◽  
pp. 248-261 ◽  
Author(s):  
Jadranka Dunđerski ◽  
Gordana Matić
Keyword(s):  
Glucocorticoid Receptor ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Immunosuppressive Agents ◽  
Receptor Protein ◽  
Target Cells ◽  
Antiinflammatory Drugs ◽  
Wide Range ◽  
Health And Disease

Glucocorticoid Receptor in Health and DiseaseGlucocorticoid hormones are essential for life, have a vital place in the treatment of inflammatory and autoimmune diseases and are increasingly implicated in the pathogenesis of a number of common disorders. Their action is mediated by an intracellular receptor protein, the glucocorticoid receptor (GR), functioning as a ligand-inducible transcription factor. Multiple synthetic glucocorticoids are used as potent antiinflammatory and immunosuppressive agents, but their therapeutic usefulness is limited by a wide range and severity of side-effects. One of the most important pharmaceutical goals has been to design steroidal and non-steroidal GR ligands with profound therapeutic efficacy and reduced unwanted effects. The therapeutic benefit of glucocorticoid agonists is frequently compromised by resistance to glucocorticoids, which may depend on: access of the hormones to target cells, steroid metabolism, expression level and isoform composition of the GR protein, mutations and polymorphisms in the GR gene and association of the receptor with chaperone proteins. The major breakthrough into the critical role of glucocorticoid signaling in the maintenance of homeostasis and pathogenesis of diseases, as well as into the molecular mechanisms underlying the therapeutic usefulness of antiinflammatory drugs acting through the GR is expected to result from the current progress in large-scale gene expression profiling technologies and computational biology.

Early interactions ofEntamoeba histolyticatrophozoites with parenchymal and inflammatory cells in the hamster liver: an immunocytochemical study

2002 ◽  
Vol 48 (2) ◽  
pp. 123-131 ◽  
Author(s):  
J Ventura-Juárez ◽  
R Campos-Rodríguez ◽  
V Tsutsumi
Keyword(s):  
Endothelial Cells ◽  
Entamoeba Histolytica ◽  
Close Contact ◽  
Inflammatory Cells ◽  
Ultrastructural Level ◽  
Target Cells ◽  
Nonparenchymal Cells ◽  
Hepatic Cells ◽  
Pmn Leukocytes ◽  
Parenchymal Cells

We studied the early in situ interactions of live and fixed Entamoeba histolytica trophozoites with hamster hepatic parenchymal and inflammatory cells using immunoperoxidase and immunoelectronmicroscopy. Close contact between trophozoites and endothelial cells and the diffusion of amoebic molecules from trophozoites towards nearby endothelial cells and distant hepatocytes were observed. The inflammatory cells around the amoebae and the remnants of parenchymal cells and hepatocytes located close to the lesion had a positive stain for amoebic molecules. In the amoebae, at the ultrastructural level, molecules were attached to the membranes and inside the vesicles. These molecules were apparently released into the space formed between the parasite and the endothelial cells. The endothelial cells and the nearby and distant hepatocytes captured amoebic molecules, and later they became necrotic. Contrarily, when fixed amoebae were inoculated, amoebic molecules were captured by endothelial cells and polymorphonuclear (PMN) leukocytes, but neither suffered any damage. In this work, we are presenting evidence clearly showing that some molecules of the amoeba can diffuse away long distances causing cytotoxic effects and even necrosis on hepatic cells of hamster liver without the need of the trophozoite being in close contact with the target cells. They also may promote lytic or proinflammatory effects by inducing the secretion of enzymes or cytokines in other nonparenchymal cells, like PMN leukocytes and endothelial cells. Our results suggest that the accepted mechanisms of cytotoxicity by amoebae are not exclusively restricted to the following sequence: adhesion, phagocytosis, and necrosis.Key words: amoebiasis, Entamoeba histolytica, liver, hamster, immunocytochemistry.

Tumour-targeted drug and gene delivery: principles and concepts

2004 ◽  
Vol 6 (19) ◽  
pp. 1-17 ◽  
Author(s):  
Jim Cassidy ◽  
Andreas G. Schätzlein
Keyword(s):  
Tumour Microenvironment ◽  
The Body ◽  
Target Cells ◽  
Tumour Targeting ◽  
Phenotypic Differences ◽  
Normal Tissues ◽  
Drug Molecules ◽  
Wide Range ◽  
Physical Barriers ◽  
Or Gene

Delivery systems for tumour targeting fall into two basic categories: drug conjugate systems, in which individual drug molecules are chemically modified to target them directly to the tumour; and carrier-based systems, in which the drug or gene is first packaged non-covalently into a synthetic carrier that is then targeted to the tumour. In both cases, the objective is to maximise exposure of the target cells to the drug yet minimise side effects that result from nonspecific toxicity in normal tissues. The creation of such dose differentials is based on phenotypic differences between the tumour and the rest of the body. However, although a wide range of such changes have been linked to the transformation of normal cells to cancer cells, no single common feature exists to allow unambiguous targeting to the tumour. In addition, the tumour microenvironment creates physical barriers that significantly impair transport within the tumour. It is therefore important to match the delivery requirements of the drug to the capabilities of the delivery system. In this review, a brief overview is given of the underlying concepts and principles that help guide the development of such tumour-targeting strategies.

scholarly journals Diverse properties of the mesothelial cells in health and disease

2016 ◽  
Vol 1 (2) ◽  
pp. 79-89 ◽  
Author(s):  
Kunio Kawanishi
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Fluid Transport ◽  
Reproductive Organs ◽  
Mesothelial Cells ◽  
The Body ◽  
Oxygen Species ◽  
Mesenchymal Transition ◽  
Wide Range ◽  
Health And Disease ◽  
Visceral Adipose

AbstractMesothelial cells (MCs) form the superficial anatomic layer of serosal membranes, including pleura, pericardium, peritoneum, and the tunica of the reproductive organs. MCs produce a protective, non-adhesive barrier against physical and biochemical damages. MCs express a wide range of phenotypic markers, including vimentin and cytokeratins. MCs play key roles in fluid transport and inflammation, as reflected by the modulation of biochemical markers such as transporters, adhesion molecules, cytokines, growth factors, reactive oxygen species and their scavengers. MCs synthesize extracellular matrix related molecules, and the surface of MC microvilli secretes a highly hydrophilic protective barrier, “glycocalyx”, consisting mainly of glycosaminoglycans. MCs maintain a balance between procoagulant and fibrinolytic activation by producing a whole range of regulators, can synthetize fibrin and therefore form adhesions. Synthesis and recognition of hyaluronan and sialic acids might be a new insight to explain immunoactive and immunoregulatory properties of MCs. Epithelial to mesenchymal transition of MCs may involve serosal repair and remodeling. MCs might also play a role in the development and remodeling of visceral adipose tissue. Taken together, MCs play important roles in health and disease in serosal cavities of the body. The mesothelium is not just a membrane and should be considered as an organ.

scholarly journals The Physiological Action of Picolinic Acid in the Human Brain

2009 ◽  
Vol 2 ◽  
pp. IJTR.S2469 ◽  
Author(s):  
R.S. Grant ◽  
S.E. Coggan ◽  
G.A. Smythe
Keyword(s):  
Human Brain ◽  
Physiological Function ◽  
Current Knowledge ◽  
Picolinic Acid ◽  
Kynurenine Pathway ◽  
The Body ◽  
Complete Understanding ◽  
Wide Range ◽  
Health And Disease ◽  
The Brain

Picolinic Acid is an endogenous metabolite of L-tryptophan (TRP) that has been reported to possess a wide range of neuroprotective, immunological, and anti-proliferative affects within the body. However the salient physiological function of this molecule is yet to be established. The synthesis of picolinic acid as a product of the kynurenine pathway (KP) suggests that, similar to other KP metabolites, picolinic acid may play a role in the pathogenesis of inflammatory disorders within the CNS and possibly other organs. In this paper we review the limited body of literature dealing with the physiological actions of picolinic acid in the CNS and its associated synthesis via the kynurenine pathway in health and disease. Discrepancies and gaps in our current knowledge of picolinic acid are identified highlighting areas of research to promote a more complete understanding of its endogenous function in the brain.

Tuning DO:DM ratios modulates MHC class II immunopeptidomes

2021 ◽  
Author(s):  
Niclas E Olsson ◽  
Wei Jiang ◽  
Lital N Adler ◽  
Elizabeth Mellins ◽  
Joshua E Elias
Keyword(s):  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Computational Prediction ◽  
Class Ii ◽  
The Body ◽  
Research Strategies ◽  
Mhc Ii ◽  
Wide Range ◽  
Health And Disease ◽  
Antigen Presenting

Major histocompatibility complex class II (MHC-II) antigen presentation underlies a wide range of immune responses in health and disease. However, how MHC-II antigen presentation is regulated by the peptide-loading catalyst HLA-DM (DM), its associated modulator, HLA-DO (DO), is incompletely understood. This is due largely to technical limitations: model antigen presenting cell (APC) systems that express these MHC-II peptidome regulators at physiologically variable levels have not been described. Likewise, computational prediction tools that account for DO and DM activities are not presently available. To address these gaps, we created a panel of single MHC-II allele, HLA-DR4-expressing APC lines that cover a wide range of DO:DM ratio states. Using a combined immunopeptidomic and proteomic discovery strategy, we measured the effects DO:DM ratios have on peptide presentation by surveying over 10,000 unique DR4-presented peptides. The resulting data provide insight into peptide characteristics that influence their presentation with increasing DO:DM ratios. These include DM-sensitivity, peptide abundance, binding affinity and motif, peptide length and register positioning on the source protein. These findings have implications for designing improved HLA-II prediction algorithms and research strategies for dissecting the variety of functions that different APCs serve in the body.

scholarly journals A Review of Panchamahabhuta Practiced

2018 ◽  
Vol 7 (3) ◽  
pp. 9-11
Author(s):  
M. Ulaganathani
Keyword(s):  
Natural Products ◽  
Human Body ◽  
The Body ◽  
Animal Products ◽  
Materia Medica ◽  
Treatment Principles ◽  
Wide Range ◽  
Health And Disease

Ayurveda treatment principles are based on correcting the imbalances of Panchamahabhutas in the body. Thus it becomes very important for us to understand the concept of Panchamahabhuta, especially with an approach of treatment perspective. Since the human body and the nature are both created from the Panchamahabhutas, Ayurveda considers all substances found in the nature as medicine; provided that it is used for explicit indications and with suitable formulations. Therefore, it utilizes a wide range of materia medica mostly natural products viz. herbs, minerals, animal products and marine originates. They are used for indications in different conditions of health and disease. This reviewed study intends to demonstrate how Panchabhautika Chikitsa is conceptualized and practiced in various disorders.

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