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Related Concept Videos

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

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Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
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Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

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Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
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Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

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Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
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Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
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Histone Variants at the Centromere02:30

Histone Variants at the Centromere

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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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Common Ion Effect03:24

Common Ion Effect

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Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Châtelier’s principle. Consider the dissolution of silver iodide:
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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
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Rare and common variant discovery in complex disease: the IBD case study.

Guhan R Venkataraman1, Manuel A Rivas1

  • 1Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, USA.

Human Molecular Genetics
|August 1, 2019
PubMed
Summary

Genetic research has uncovered over 200 sites linked to inflammatory bowel disease (IBD). Advanced technologies are improving the identification of rare genetic variants, aiding in understanding IBD causes and treatments.

Keywords:
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Area of Science:

  • Genetics
  • Gastroenterology
  • Genomic Medicine

Background:

  • Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, represents a substantial health challenge with 70,000 new US cases annually.
  • Genetic research has historically focused on identifying variants contributing to complex diseases like IBD.

Observation:

  • This review traces the evolution of genetic variant discovery methods, from microsatellites to whole-genome sequencing, emphasizing the shift towards rare variant detection.
  • Technological advancements and increased availability of population variation data have accelerated the discovery of IBD-associated loci.

Findings:

  • Over 200 IBD-associated genetic loci have been identified, with a growing emphasis on rare variants.
  • Key rare-variant discoveries in genes such as NOD2, IL23R, CARD9, RNF186, and ADCY7 have been crucial for understanding IBD pathogenesis.
  • Methods for rare variant discovery have significantly improved in power and ascertainment.

Implications:

  • Continued advancements in rare-variant discovery are anticipated to further elucidate the genetic underpinnings of IBD.
  • A deeper understanding of IBD's genetic basis promises to enhance diagnostic accuracy, prognostic prediction, therapeutic strategies, and patient surveillance.
  • This genetic insight is vital for advancing the treatment of IBD and other complex diseases.