Background Aims: The beneficial effect of human (h) mesenchymal stromal cell (MSC) transplantation in a variety of cell-based intervention strategies is widely believed to be because of paracrine mechanisms. The modification of hMSC cytokine and growth-factor expression patterns were studied following exposure to lipopolysaccharide (LPS) and tissue homogenates (representing tissue debris) from normal and pathologic tissues.
Methods: Human bone marrow-derived MSC were stimulated with LPS or exposed to homogenate from normal or pathologic rat spinal cord or heart. The expression profiles of a number of cytokines and growth factors were investigated using quantitative reverse transcription (RT)-polymerase chain reaction (PCR) with human-specific primers. The effects of tissue homogenates on hMSC proliferation and migratory behavior were also investigated.
Results: Stimulation of hMSC with LPS resulted in an up-regulation of interleukin (IL)-1β, IL-6 and IL-8. However, the pattern of up-regulation varied between donor samples. Furthermore, LPS treatment resulted in a donor-dependent alteration of growth factor expression. Induction of a shift in expression pattern was not observed following exposure to homogenates from either normal or pathologic tissues. Tissue homogenates did stimulate cell proliferation, but not migration.
Conclusions: The hMSC expression pattern is apparently stable, even when cells are confronted by debris from different tissue types. However, treatment of hMSC with LPS is able to change the expression of cytokines and growth factors in a donor-dependent manner that may enhance their potential use in regenerative medicine.
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Purpura fulminans (PF) is a rare but devastating complication of sepsis characterized by a highly thrombotic subtype of disseminated intravascular coagulation (DIC). A medical emergency, PF cases often require the involvement of consultant hematologists to assist with diagnosis and management of patients who are in a highly dynamic and deteriorating clinical situation. Patients who survive past the first 24 to 72 hours often die from complications of unchecked thrombosis rather than from shock, and survivors are usually left with severe scarring and tissue loss.
View Article and Find Full Text PDFBackground: Abnormal protein depositions of amyloid β and tau are present in the nasal cavity in patients with Alzheimer's disease. This finding raises an idea that nasal tissues would be a promising source of diagnostic biomarkers for Alzheimer's disease. However, the amounts of amyloid β and tau are extremely small, making it difficult to quantify the levels using conventional methods such as ELISA, and thus it is challenging to utilize them for the diagnostic biomarkers.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Background: [F]MK-6240 was developed for PET imaging of AD tau pathology, but the exact molecular signature of specific binding remains unclear. This study quantified levels of four phospho-tau forms and total tau in postmortem brain tissues from [F]MK-6240 imaged cases to investigate associations with antemortem [F]MK-6240 PET.
Methods: This study included four participants from the Wisconsin ADRC or WRAP with antemortem [F]MK-6240 and [C]PiB PET imaging and postmortem brain tissue obtained on average 32-months after imaging (Table 1).
Background: The retina, an integral part of the central nervous system, can exhibit protein accumulation (Aβ and pTau) associated with neurodegenerative diseases such as Alzheimer's disease (AD). Biochemical analysis revealed the existence of a distinct primary retinal tauopathy (PReT), differing from AD and primary age-related tauopathy (PART) brain lysates, suggesting it as a potential precursor for AD tauopathy with possible diagnostic value. However, it remains unclear whether retinal pTau pathology can spread from the eye into the brain.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non-Hispanic White (NHW) population. To address this, Accelerating Medicines Partnership in AD (AMP-AD) aimed to promote inclusivity in multi-omics AD research, to unravel unique molecular signatures and pathways. The study aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial groups.
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