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Infection01:20

Infection

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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
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Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

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The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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Pneumonia II: Pathophysiology01:29

Pneumonia II: Pathophysiology

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The pathophysiology of pneumonia involves the following steps:
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Stages of Infection01:26

Stages of Infection

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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
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Video Experimental Relacionado

Updated: Jan 8, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Ciencia Básica y Patogénesis

Zeynep Sarica1, Kevin P Kotredes1, Alaina M Reagan1

  • 1The Jackson Laboratory, Bar Harbor, ME, USA.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Nuevos modelos de ratón que incorporan genes de riesgo de Alzheimer humanos y exposición al arsénico imitan mejor la enfermedad de Alzheimer de inicio tardío (LOAD). Estos modelos muestran cambios cerebrales similares a la LOAD humana, lo que ayuda al descubrimiento de biomarcadores y dianas terapéuticas.

Palabras clave:
modelos de ratónenfermedad de Alzheimer de inicio tardíogenes de riesgo humanoexposición al arsénicobiomarcadoresdianas terapéuticas

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Área de la Ciencia:

  • Neurociencia; Genética; Toxicología

Sus antecedentes:

  • Los modelos de ratón actuales representan de manera inadecuada la complejidad genética y la variabilidad clínica de la enfermedad de Alzheimer de inicio tardío (LOAD).
  • La variante MTHFR 677C>T y los factores ambientales como la exposición al arsénico se implican en la susceptibilidad a la LOAD.
  • El desarrollo de modelos mejorados es crucial para avanzar en el desarrollo de terapias preclínicas para la LOAD.

Objetivo del estudio:

  • Generar y evaluar nuevos modelos de ratón que incorporen alelos de riesgo de LOAD humana e insultos ambientales.
  • Evaluar la utilidad de estos modelos para recapitular aspectos clave de la patología y las firmas moleculares de la LOAD humana.
  • Identificar biomarcadores potenciales y dianas terapéuticas para la LOAD.

Principales métodos:

  • Generación de ratones LOAD2.Mthfr*677C>T homocigotos para los alelos humanizados MTHFR*677C>T, Abeta, APOEe4 y Trem2*R47H.
  • Exposición de ratones envejecidos a trióxido de arsénico en agua potable, seguida de análisis longitudinales de comportamiento, biométricos y de tejidos en el punto final (transcriptómica, proteómica, neuropatología).
  • Evaluación de la desintoxicación del arsénico mediante especiación de orina utilizando LC-ICP-MS.

Principales resultados:

  • La variante MTHFR*677C>T condujo a una reducción de la actividad enzimática y a niveles elevados de homocisteína en sangre.
  • Los ratones LOAD2.Mthfr*677C>T envejecidos exhibieron firmas transcripcionales y proteómicas cerebrales significativamente alineadas con la AD humana.
  • La exposición al arsénico mejoró aún más la alineación de las firmas transcripcionales con la AD humana, siendo el DMA la principal especie de arsénico en la orina.

Conclusiones:

  • La variante Mthfr*677C>T y la exposición al arsénico modifican los perfiles moleculares del cerebro, correlacionándose con la LOAD humana.
  • Estos modelos de ratón modificados demuestran utilidad para capturar la complejidad de la LOAD humana.
  • El estudio apoya el uso de estos modelos para el descubrimiento de biomarcadores y dianas terapéuticas para la LOAD.