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This might allow cells to specifically recognise the age of a matrix.
It appears thus that the expression of genes coding for extracellular matrix macromolecules is under age-dependent regulation.
We found that as the nucleus increases in size and becomes more round with age, the qualitative pattern of the prominent nuclear matrix proteins does not appear to undergo major changes with age.
AGE modification of matrix proteins is also able to disrupt matrix-matrix and matrix-cell interactions, contributing to their profibrotic action.
William Reeves is thus a quintessential Californian, a fact of which, all who know him realize, he is quietly very proud.

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How can i create the model of immune-aging animal?
5 answers
To create a model of immune-aging in animals, utilizing nonhuman primates (NHPs) like common marmosets is highly recommended. NHPs closely mimic human physiological changes with aging. These animals exhibit clear signs of immunosenescence, including T cell senescence, alterations in B cell compartments, and decline in NK cells, resembling age-related changes in humans. While traditional rodent models have provided insights into immune senescence, NHPs offer advantages due to their genetic and physiological similarity to humans, making them valuable for studying interventions to reverse immune aging and develop tailored vaccine strategies for the elderly. By incorporating data from NHPs, researchers can better understand the mechanisms underlying age-associated dysregulated immunity and develop effective interventions to improve immune function in aging populations.
What are the specific factors that affect the 3D printed PCL polymer scaffolds in bone tissue engineering?
5 answers
The mechanical properties of 3D printed PCL polymer scaffolds in bone tissue engineering are influenced by various factors. Scaffold design parameters such as height and internal structure play a crucial role. Additionally, the incorporation of nano-hydroxyapatite (nHAp) into PCL scaffolds affects their mechanical and biological performance. The pore size and internal structure of the scaffold also impact osteoblast performance, with staggered scaffolds showing better support for cellular activities. Furthermore, the addition of bioceramics like hydroxyapatite (HA) and β tricalcium phosphate (β-TCP) along with carbon nanotubes (CNTs) in PCL-based composite scaffolds influences gene expression related to osteogenesis and inflammatory responses, ultimately affecting tissue formation and mineralization. These factors collectively determine the effectiveness of 3D printed PCL polymer scaffolds in bone tissue engineering applications.
What is the role of vitamin C in collagen synthesis?
5 answers
Vitamin C plays a crucial role in collagen synthesis by modulating various aspects of the process. It acts as a cofactor for enzymes involved in collagen biosynthesis, such as monooxygenases and dioxygenases. In the context of myocardial infarction (MI), vitamin C has been shown to enhance the synthesis of collagen types I and III by cardiac fibroblasts, promoting tissue healing. Additionally, in glioblastoma cells, vitamin C uptake leads to collagen biosynthesis, impacting tumor development and progression. Studies on skin fibroblasts have demonstrated that vitamin C derivatives can stimulate collagen production more effectively than vitamin C alone, highlighting its importance in skin health and anti-aging applications. Furthermore, lipophilic derivatives of vitamin C have been developed to improve skin diffusion and delivery, promoting collagen synthesis in human skin.
How ezh2 is regulated in progeria?
5 answers
EZH2 regulation in progeria involves its downregulation and subsequent impact on cellular processes. Studies show that EZH2 is significantly decreased in aged and fibrotic tissues, leading to replicative senescence in atrial fibroblasts (AFs). This downregulation is associated with the acceleration of replicative senescence in AFs through mechanisms involving histone modifications and gene transcription suppression. Additionally, EZH2 dysregulation due to mutation and under-expression is linked to specific subtypes of acute myeloid leukemia (AML), affecting patient survival outcomes. The interaction of EZH2 with other chromatin modification factors like LSD1, DNMT1, and HDAC1 further influences neuronal differentiation in cancer cells, highlighting its role in tumorigenesis. Therefore, the regulation of EZH2 in progeria involves intricate molecular mechanisms impacting cellular senescence and disease progression.
What is the relationship between p53 and heparan sulfate?
5 answers
The relationship between p53 and heparan sulfate (HS) is intricate and multifaceted. Studies have shown that sulfated glycosaminoglycans, particularly highly sulfated domains of HS (HS S-domains), play a crucial role in the pathology of protein aggregation diseases involving p53. Furthermore, p53 has been identified as a direct transcriptional regulator of the SULF2 gene, which encodes an enzyme involved in modulating growth factor binding and acts as a tumor suppressor. Additionally, proper HS status is essential for preventing cellular senescence by fine-tuning the fibroblast growth factor receptor (FGFR) signaling pathway, with p53 and p21 accumulation being crucial for this process. Moreover, wild-type p53 has been found to bind to the heparanase promoter and inhibit its activity, suggesting a regulatory role of p53 in controlling heparanase expression.
What materials have been used with coaxial, co-axial or core/shell bioprinting?
5 answers
Various materials have been utilized in coaxial, co-axial, or core/shell bioprinting techniques. These include alginate, methylcellulose, collagen-fibrin matrices, gelatin, polycaprolactone (PCL), sodium alginate (SA), hydrogels, gelatin methacryloyl (GelMA), and hydroxyapatite (HAp) nanoparticles. Alginate and methylcellulose were used for the shell compartment in liver sinusoid-like models, while PCL and SA were employed for shell/core scaffolds in coaxial cryogenic printing. Gelatin, GelMA, alginate, and HAp nanoparticles were utilized for creating osteon-like structures in coaxial bioprinting. Additionally, alginate was used to create perfusable double-channel filaments for vascularized structures. These diverse materials play crucial roles in achieving specific functionalities and structural complexities in bioprinted constructs.
What is the combined name for the endothelial cells and basement membrane called?
4 answers
The combined name for endothelial cells and the basement membrane is referred to as the endothelial cell basement membrane (BM). Basement membranes are essential extracellular matrices underlying endothelial cells, providing structural support and influencing cell behavior. Studies highlight the critical role of basement membranes in regulating immune cell infiltration and phenotype at the endothelial interface, affecting disease severity. Furthermore, engineered basement membranes have been developed to mimic native BM properties, aiding in tissue repair and regeneration, such as in corneal endothelium engineering for potential transplantation. Proper deposition and assembly of vascular basement membranes by both endothelial cells and pericytes are crucial for vessel stability and maturation during vascular development.
What is the opposite of oxidative stress?
4 answers
The opposite of oxidative stress can be considered as a state where there is a balance between the production of reactive oxygen species and antioxidants, leading to cellular homeostasis and redox signaling. While oxidative stress results from an imbalance favoring the production of reactive oxygen species over antioxidants, the opposite state involves a harmonious equilibrium between pro-oxidants and antioxidants at the cellular level. This equilibrium ensures that the damaging effects of reactive oxygen species are counteracted by the protective mechanisms of antioxidants, maintaining cellular health and preventing oxidative damage. In essence, the opposite of oxidative stress signifies a condition where the body's antioxidant defenses effectively neutralize reactive oxygen species, promoting overall cellular well-being and functionality.
Does increase in oxidative phosphorylation prevent or reduce cellular ageing?
5 answers
Increased oxidative phosphorylation (OXPHOS) in response to genotoxic stress and mitochondrial dysfunction plays a dual role in cellular aging. On one hand, chronic endogenous and acute exogenous genotoxic stress can lead to increased OXPHOS as an adaptive response to DNA damage, illustrating a link between genotoxic stress and energy metabolism. Conversely, primary mitochondrial oxidative phosphorylation defects can result in hypermetabolism, accelerating biological aging through increased energy expenditure, mitochondrial DNA instability, and activation of stress responses. Additionally, excessive mitochondrial reactive oxygen species (mROS) production can induce pathways that protect mitochondria, inhibit cell death, and increase lifespan, but can also lead to oxidative damage that accelerates aging, suggesting a complex interplay between OXPHOS, mROS, and cellular aging.
What is the typical characteristic structure of TRAFAC GTPases?
5 answers
The typical characteristic structure of TRAFAC GTPases involves a modular organization with domains essential for their function in ribosome assembly and translation processes. These GTPases undergo conformational changes in response to GTP hydrolysis, acting as molecular switches. They contain conserved domains like the P-loop for GTP binding and hydrolysis, as well as additional domains such as the TGS domain with unknown functions. Furthermore, TRAFAC GTPases exhibit unique structural features like the presence of helix-turn-helix and S5D2L domains, which are crucial for their interaction with other proteins like DFRP. Overall, the structural complexity of TRAFAC GTPases allows them to play pivotal roles in ribosome biogenesis and translation regulation.
Does cddo-me (bardoxolone-methyl) have an effect on nrf2 target genes in hepg2 cells?
5 answers
Bardoxolone methyl (CDDO-Me) has a significant impact on NRF2 target genes in various cell types. Studies have shown that CDDO-Me activates the NRF2 pathway, leading to the induction of NRF2 target gene transcripts and enzyme activity. In the context of lung cancer, CDDO-Me influences macrophage polarization by modulating the expression of M1 and M2 macrophage markers in a Nrf2-dependent manner. Additionally, CDDO-Me has been found to reprogram bone marrow-derived macrophages towards a tumor-inhibiting phenotype by altering the expression of specific markers. Furthermore, CDDO-Me treatment has been shown to upregulate antioxidant enzymes and induce apoptosis, potentially protecting against cellular senescence in renal cells. Overall, CDDO-Me demonstrates a consistent effect on NRF2 target genes across different cellular contexts.