Publications by authors named "Samuel T Pasco"

Vaccines are one of the greatest achievements of modern medicine. Due to their safer profile, the latest investigations usually focus on subunit vaccines. However, the active component often needs to be coupled with an adjuvant to be effective and properly trigger an immune response.

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The initial exposure to pathogens and commensals confers innate immune cells the capacity to respond distinctively upon a second stimulus. This training capacity might play key functions in developing an adequate innate immune response to the continuous exposure to bacteria. However, the mechanisms involved in induction of trained immunity by commensals remain mostly unexplored.

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We disclose here a panel of small-molecule TLR4 agonists (the series) whose structure is derived from previously developed TLR4 ligands ( series). The new molecules have increased chemical stability and a shorter, more efficient, and scalable synthesis. The series showed selective activity as TLR4 agonists with a potency similar to .

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COVID-19 is a systemic infectious disease that may affect many organs, accompanied by a measurable metabolic dysregulation. The disease is also associated with significant mortality, particularly among the elderly, patients with comorbidities, and solid organ transplant recipients. Yet, the largest segment of the patient population is asymptomatic, and most other patients develop mild to moderate symptoms after SARS-CoV-2 infection.

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Article Synopsis
  • Hepatic ischemia-reperfusion injury (IRI) is a major cause of early organ failure post-liver transplantation, particularly affecting aged or compromised donor livers due to restricted blood supply and damage to mitochondria.
  • Researchers investigated the effects of silencing a protein called methylation-controlled J protein (MCJ), which negatively regulates mitochondrial activity, finding that this leads to faster liver regeneration and reduced injury in mice models.
  • The study suggests that targeting MCJ can improve mitochondrial respiration and cell survival after IRI, offering potential therapeutic strategies for patients with metabolic issues and liver disease.
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Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens.

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