Publications by authors named "O Gorka"

Article Synopsis
  • Mitochondria play complex roles in two different cell death pathways: apoptosis and pyroptosis, particularly regarding NLRP3 inflammasome activation, but their exact mechanisms are not well understood.
  • The study found that activating NLRP3 while inhibiting apoptosis occurs when cells are under stress from various stimuli like nigericin and viruses, as these activators affect mitochondrial function rather than just triggering inflammasome activation.
  • NLRP3 activation needs a combination of signals—one from disrupted mitochondrial processes and another from specific NLRP3 activators—suggesting that both oxidative phosphorylation inhibition and apoptosis suppression influence cell fate.
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Photoimmunotherapy (PIT) combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers (PS) and is a promising new cancer therapy. We designed and synthesized, in a highly convergent manner, the silicon phthalocyanine dye WB692-CB2, which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines. In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen (PSMA).

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3' untranslated regions (3' UTRs) are critical elements of messenger RNAs, as they contain binding sites for RNA-binding proteins (RBPs) and microRNAs that affect various aspects of the RNA life cycle including transcript stability and cellular localization. In response to T cell receptor activation, T cells undergo massive expansion during the effector phase of the immune response and dynamically modify their 3' UTRs. Whether this serves to directly regulate the abundance of specific mRNAs or is a secondary effect of proliferation remains unclear.

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Article Synopsis
  • Differentiated podocytes are sensitive to oxidative stress and cellular waste, with their loss indicating renal disease progression and aging.
  • The study identifies ARFIP2 as a crucial regulator of autophagy and mitophagy in podocytes, utilizing both in vitro (human cell lines) and in vivo (mouse models) methods to investigate its role.
  • Findings reveal that ARFIP2 deficiency hampers autophagy, disrupts mitochondrial function, and exacerbates kidney damage in diabetic mice, highlighting its importance in podocyte health and renal maintenance.
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Article Synopsis
  • Exposure to fine particulate matter (PM) from air pollution leads to respiratory and cardiovascular issues by activating the NLRP3 inflammasome, which triggers inflammation and release of IL-1β, a key inflammatory cytokine.
  • The activation of the inflammasome is dependent on the amount and type of PM, with Residual Oil Fly Ash (ROFA) being particularly effective in inducing IL-1β release, while other PM types were less effective.
  • The study reveals that mechanisms like lysosomal rupture and mitochondrial dysfunction contribute to IL-1β release, highlighting the complex interplay of cellular damage and immune response to specific air pollutants like ROFA.
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