We previously reported that membrane-type 5-matrix metalloproteinase (MT5-MMP) deficiency not only reduces pathological hallmarks of Alzheimer's disease (AD) in 5xFAD (Tg) mice in vivo but also impairs interleukin-1 beta (IL-1β)-mediated neuroinflammation and Aβ production in primary Tg immature neural cell cultures after 11 days in vitro. We now investigate the effect of MT5-MMP on incipient pathogenic pathways that are activated in cortical primary cultures at 21-24 days in vitro (DIV), during which time neurons are organized into a functional mature network. Using wild-type (WT), MT5-MMP (MT5), 5xFAD (Tg), and 5xFADxMT5-MMP (TgMT5) mice, we generated primary neuronal cultures that were exposed to IL-1β and/or different proteolytic system inhibitors.
View Article and Find Full Text PDFPanniculitides are a group of inflammatory disorders of the subcutaneous fat that have been reported as a rare complication of both a serine threonine kinase BRAF inhibitor monotherapy and BRAF inhibition in combination with a mitogen activated protein kinase (MEK) inhibitor combination therapy used to treat metastatic melanoma. The cutaneous manifestations of BRAF and BRAF/MEK therapies have been well documented, but neutrophilic panniculitis remains a less common complication with fewer case reports. Physician awareness of this complication when following patients on similar targeted therapies can decrease delays in appropriate management.
View Article and Find Full Text PDFClearance of residual Host Cell Proteins (HCPs) is critical for the manufacturing processes of biotherapeutics. HCPs have the potential to impact product efficacy and quality, posing a risk to patient safety. It is therefore essential to be able to both identify and quantitate HCPs throughout drug development, even if the proteins are present in low concentrations.
View Article and Find Full Text PDFThe coronavirus disease 2019 (COVID-19) pandemic had dramatic impacts throughout the United States (US). In Cameron County, Texas, along the Texas-Mexico border, the impacts of the virus were felt more severely than in most places in the US. Residents of the county, which has high rates of poverty, many multigenerational households, high levels of underlying conditions, and an uninsured population of almost 30 percent, were not only poised to be affected by the virus but also by the response policies put in place to contain it.
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