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Related Concept Videos

Complement System01:27

Complement System

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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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Antibody Actions01:26

Antibody Actions

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Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
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Immunoglobulin-like Cell Adhesion Molecules01:31

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Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
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Differentiation of Common Myeloid Progenitor Cells01:15

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Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
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Anaphase Promoting Complex00:50

Anaphase Promoting Complex

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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Measuring the 50% Haemolytic Complement CH50 Activity of Serum
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Colon-targeted complement C5a1 receptor inhibition using pH-sensitive nanoparticles ameliorates experimental colitis.

Cedric S Cui1, Titaya Lerskiatiphanich1, Xaria X Li1

  • 1School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

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A new colon-targeted drug delivery system effectively targets the C5a1 receptor, showing promise for treating inflammatory bowel disease (IBD) and ulcerative colitis.

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Area of Science:

  • Immunology
  • Gastroenterology
  • Drug Delivery Systems

Background:

  • The complement system and C5a receptor (C5aR1) signaling are implicated in inflammatory bowel disease (IBD) pathogenesis.
  • C5aR1 antagonists are potential therapeutics, but clinical use is hindered by rapid metabolism.

Purpose of the Study:

  • To develop a colon-targeted formulation of the C5aR1 antagonist PMX205 for IBD treatment.
  • To evaluate the efficacy of this novel drug delivery system in preclinical models of colitis.

Main Methods:

  • Examined C5aR1 expression in ulcerative colitis patient biopsies.
  • Encapsulated PMX205 into pH-sensitive polymers for targeted colon delivery.
  • Assessed nanoparticle toxicity, drug release, and in vivo biodistribution.
  • Evaluated therapeutic efficacy in a dextran sodium sulfate-induced colitis mouse model.

Main Results:

  • C5aR1 was upregulated in active ulcerative colitis lesions.
  • PMX205 nanoparticles were non-toxic and released active drug in simulated colon fluid.
  • Nanoparticles demonstrated rapid colon uptake and persistence in mice.
  • Oral administration of PMX205 nanoparticles significantly ameliorated colitis symptoms and pathology, outperforming unformulated PMX205.

Conclusions:

  • A novel colon-targeted formulation of PMX205 nanoparticles offers a potent therapeutic strategy for IBD.
  • This approach facilitates the clinical translation of C5aR1 antagonists for ulcerative colitis and other IBD conditions.