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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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Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses

Published on: June 14, 2020

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Ciencia básica y patogénesis

Elizabeth S Fisher1, Kate Tubbesing1, Katherine Stevens1

  • 1Neural Stem Cell Institute, Albany, NY, USA.

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

La variante de la fosfolipasa D3 (PLD3) impacta la función vascular y la inflamación, afectando a las células endoteliales y murales. Este estudio revela el papel de PLD3 en la patogénesis de la enfermedad de Alzheimer, particularmente en el remodelado vascular y el procesamiento de la proteína precursora amiloide.

Palabras clave:
fosfolipasa D3enfermedad de Alzheimerfunción vascularcélulas endotelialescélulas muralesremodelado vascularprocesamiento de APP

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Área de la Ciencia:

  • Neurociencia; Genética; Biología Vascular

Sus antecedentes:

  • Los estudios de asociación del genoma completo (GWAS) vinculan los polimorfismos de un solo nucleótido (SNP) con la enfermedad de Alzheimer de inicio tardío (LOAD).; Una variante rara de la fosfolipasa D3 (PLD3) (p.A442A) duplica el riesgo de LOAD y está implicada en el procesamiento de la proteína precursora de amiloide (APP).; Investigaciones previas sugirieron el papel de PLD3 en la función vascular de ratones, pero sus acciones específicas en las células endoteliales (CE) y las células murales eran desconocidas.

Objetivo del estudio:

  • Investigar el impacto de la variante PLD3 en la función vascular y la patogénesis de la enfermedad de Alzheimer (EA).; Explorar el papel de PLD3 en las células endoteliales (CE) y las células murales utilizando modelos de ratón y células madre pluripotentes inducidas (iPSC) humanas.

Principales métodos:

  • Se utilizaron ratones knockout (KO) APP/PS1xPLD3 y se analizaron datos de secuenciación de ARN (RNA-seq) cortical.; Se emplearon iPSC humanas diferenciadas en células endoteliales y murales, cultivadas en modelos de redes vasculares 2D y 3D.; Se evaluaron los efectos de la variante y la reducción de PLD3 mediante RNA-seq, inmunohistoquímica, ensayos de liberación de citoquinas y detección de impedancia de sustrato de células eléctricas (ECIS) para la función de barrera de las CE.

Principales resultados:

  • En ratones APP/PS1xPLD3 KO, las vías vasculares y de inflamación se regularon a la baja, mientras que las vías de degradación de proteínas se regularon al alza.; Las CÉLULAS endoteliales derivadas de iPSC con la variante o la reducción de PLD3 mostraron una división celular y un procesamiento de APP alterados, lo que afectó a los genes de AD-GWAS.; Las células murales con la variante PLD3 exhibieron un remodelado alterado de la matriz extracelular (por ejemplo, FN1, MMP25).; Los modelos vasculares 3D con la variante PLD3 mostraron una liberación alterada de Interleucina-8 (IL-8), lo que sugiere implicaciones para el remodelado vascular.

Conclusiones:

  • PLD3 influye significativamente en la función vascular y la inflamación en ratones, contribuyendo potencialmente a la patogénesis de la enfermedad de Alzheimer (EA).; En modelos vasculares derivados de iPSC humanas, PLD3 regula la proliferación de CE, el procesamiento de APP y la organización de la matriz de células murales.; La variante PLD3 puede inducir remodelado o inestabilidad vascular, lo que justifica una mayor investigación de los mecanismos subyacentes para una posible focalización terapéutica.