The presence ofAspergillusmycotoxins has been confirmed in various feed and food. They represent a hid-den threat that cannot be completely prevented. In animal husbandry, they impair their productive health and, in hu-man nutrition, they can cause acute or chronic health com-plications. This article provides an overview of the most important secondary metabolites of the genus Aspergillusin terms of their occurrence, toxicity and physico-chemical properties.

• MeSH
• aflatoxiny * chemie   škodlivé účinky   toxicita   MeSH
• Aspergillus * chemie   metabolismus   patogenita   MeSH
• gliotoxin chemie   škodlivé účinky   toxicita   MeSH
• karcinogeny chemie   MeSH
• lidé MeSH
• ochratoxiny * chemie   škodlivé účinky   toxicita   MeSH
• patulin chemie   škodlivé účinky   toxicita   MeSH
• sterigmatocystin chemie   škodlivé účinky   toxicita   MeSH
• Check Tag
• lidé MeSH

A leading pharmacological strategy toward HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with latency reversal agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs, we used fungal secondary metabolites as a source of bioactive molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the positive transcription elongation factor b (P-TEFb) inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex, to be significantly reduced upon GTX treatment of CD4+ T cells. GTX directly disrupted 7SK snRNP by targeting La-related protein 7 (LARP7), releasing active P-TEFb, which phosphorylated RNA polymerase II (Pol II) C-terminal domain (CTD), inducing HIV transcription.

• MeSH
• gliotoxin * metabolismus   MeSH
• HeLa buňky MeSH
• HIV infekce * farmakoterapie   MeSH
• HIV-1 * metabolismus   MeSH
• lidé MeSH
• pozitivní transkripční elongační faktor b genetika   metabolismus   MeSH
• proteiny vázající RNA metabolismus   MeSH
• ribonukleoproteiny malé jaderné chemie   MeSH
• ribonukleoproteiny MeSH
• transkripční faktory metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Activated hepatic stellate cells (HSC) are a major source offibrous proteins in cirrhotic liver. Inducing or accelerating their apoptosis is a potential way of liver fibrosis treatment. Extracellular matrix (ECM) surrounding cells in tissue affects their differentiation, migration, proliferation and function. Type I collagen is the main ECM component in fibrotic liver. We have examined how this protein modifies apoptosis of normal rat HSC induced by gliotoxin, cycloheximide and cytochalasin D in vitro and spontaneous apoptosis of HSC isolated from CCl4-damaged liver. We have found that type I collagen gel enhances HSC apoptosis regardless of the agent triggering this process.

• MeSH
• apoptóza účinky léků   MeSH
• buněčné kultury MeSH
• chlorid uhličitý MeSH
• cykloheximid MeSH
• cytochalasin D MeSH
• gliotoxin MeSH
• jaterní cirhóza patologie   MeSH
• jaterní hvězdicovité buňky účinky léků   patologie   MeSH
• kolagen typu I farmakologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Sprague-Dawley MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH