Health economics perspective: Genetic mutation test reports utilize mathematics and computer science to study and analyze cryptographic encryption strategies

Health economics is the focus of current research, and genetic testing has become an emerging and universal means of disease surveillance based on the ever-changing perspective of the global basic medicine in the field of cellular genetics. But genes represent the genetic information of the human physiology, and therefore must be handled in a confidential manner. With the use of current computational and codon knowledge structures, the authors propose and report strategies for problem solving in computer medicine based on genetic properties

Protein kinase C in regulation of exocytosis

Exocytosis, by which secretory vesicles are directed to outer cell membrane and subsequently discharge their contents upon triggering, is an important and ubiquitous cellular process responsible for secretion of neurotransmitters from neurons and hormones from endocrine cells. Exocytosis is highly regulated through the orchestrated actions of various proteins and lipids. It has been well recognized that protein kinase Cs (PKCs) are active regulators of exocytosis via phosphorylating multiple key proteins in the exocytotic cascade. The specific actions mediated by PKCs, however, have not been fully elucidated. The challenges mainly lie in the following aspects: 1) large variety of PKC isoforms and dubious specificity of the commonly used pharmacological tools; 2) large variety of PKC substrates; 4) difficulties to isolate the molecular steps in the highly dynamic exocytotic process.DOCTOR OF PHILOSOPHY (SCBE

Involvement of PKC-alpha in PMA-induced facilitation of exocytosis and vesicle fusion in PC12 cells

Phorbol-12-myristate-13-acetate, a stable analog of the important signaling membrane lipid diacylglycerol (DAG), is known to potentiate exocytosis and modulate vesicle fusion kinetics in neurons and endocrine cells. The exact mechanisms underlying the actions of PMA, however, is often not clear, largely because of the diversity of the DAG/PMA receptors involved in the exocytotic process, which include, most notably, various isoforms of protein kinase C (PKC). In this study, the roles of PKCa in PMA-mediated regulation of exocytosis were investigated by over-expressing wild-type PKCa (wt-PKCa) or dominant negative PKCa (dn-PKCa). Amperometric measurements based on carbon fiber microelectrodes demonstrated that PKCa has a key role in the PMA-mediated facilitation of exocytosis and vesicle fusion in neuroendocrine PC12 cells.Accepted versio

Effects of phorbol ester on vesicle dynamics as revealed by total internal reflection fluorescence microscopy

Exocytosis of neurotransmitter or hormone-filled vesicles is a highly dynamic process regulated by various proteins and lipids. As mainly revealed indirectly by the electrophysiological methods, exocytosis is believed to involve multiple kinetic steps in which vesicles transit from one state to another. Using total internal reflection fluorescence microscopy which enables direct visualization of individual vesicles, we developed an analytical framework to track and analyze vesicle dynamics. We demonstrated that all subplasmalemmal vesicles generally undergo constant and caged Brownian motion. And they can be classified into three populations that differ in their motion characteristics and fusion competence. Furthermore, we showed that these vesicle pools are differentially modulated by phorbol-12-myristate-13-acetate, a phorbol ester analog to endogenous diacylglycerol, through both protein-kinase- C-dependent and -independent pathways.Accepted versio

Measuring membrane capacitance during a depolarizing stimulus

Regulated by the combined actions of various proteins and lipids, exocytosis in neurons or neuroendocrine cells is a highly dynamic process. It involves the transition of secretory vesicles through distinct molecular states in a time scale of seconds and final rapid Ca dependent vesicle fusion in a time scale of milliseconds. It is critical to resolve the highly dynamic kinetic steps along the molecular cascade of exocytosis in order to pin down the specific actions of regulatory molecules and eventually decipher this complex and fundamental process.RG 41/0

PKC epsilon facilitates recovery of exocytosis after an exhausting stimulation

It has been well documented that protein kinase Cs (PKCs) play multifaceted roles in regulating exocytosis of neurotransmitters and hormones. But the isoform-specific PKC effects are still poorly elucidated mainly because of the large variety of PKC isoforms and the dubious specificity of the commonly used pharmacological agents. In the present study, based on overexpression of wild-type or dominant negative PKCε, we demonstrate in neuroendocrine PC12 cells that PKCε, but not PKCα, facilitates recovery of exocytosis after an exhausting stimulation. Specifically, PKCε mediates fast recovery of the extent of exocytosis in a phosphatidylinositol biphosphate-dependent manner, likely through enhancing the rate of vesicle delivery and reorganization of cortical actin network. In addition, PKCε promotes fast recovery of vesicle release kinetics that is slowed after a strong stimulation. These experimental results may suggest a PKC-dependent mechanism relevant to the short-term plasticity of exocytosis in both neurons and neuroendocrine cells.Accepted versio

The crosstalks between adipokines and catecholamines

Adipocytes, which secrete a spectrum of adipokines, play an integral role in metabolism via communications with other endocrine cells. In the present work, we have studied the interplays between adipokines and catecholamines, using 3T3-L1 adipocytes and PC12 cells as the cell models and an integrative experimental platform. We demonstrate that all catecholamines inhibit vesicle trafficking and secretion of leptin and resistin through β-adrenergic receptors, while leptin and resistin enhance the vesicle trafficking and secretion of catecholamines through PKC, PKA, MAPK kinase and Ca2+ dependent pathways. The crosstalks between adipokines and catecholamines were further corroborated by co-culturing 3T3-L1 adipocytes and PC12 cells. Our findings highlight the importance of adipo-adrenal axis in energy metabolism and the intricate interactions between metabolic hormones.Accepted versio

Elastin-like recombinamer-mediated hierarchical mineralization coatings on Zr-16Nb-xTi (x=4,16wt%) alloy surfaces improve biocompatibility

The biocompatibility of biomedical materials is vital to their applicability and functionality. However, modifying surfaces for enhanced biocompatibility using traditional surface treatment techniques is challenging. We employed a mineralizing elastin-like recombinamer (ELR) self-assembling platform to mediate mineralization on Zr-16Nb-xTi (x = 4,16 wt%) alloy surfaces, resulting in the modification of surface morphology and bioactivity while improving the biocompatibility of the material. We modulated the level of nanocrystal organization by adjusting the cross-linker ratio. Nanoindentation tests revealed that the mineralized configuration had nonuniformity with respect to Young's modulus and hardness, with the center areas having higher values (5.626 ± 0.109 GPa and 0.264 ± 0.022 GPa) compared to the edges (4.282 ± 0.327 GPa and 0.143 ± 0.023 GPa). The Scratch test results indicated high bonding strength (2.668 ± 0.117 N) between the mineralized coating and the substrate. Mineralized Zr-16Nb-xTi (x = 4,16 wt%) alloys had higher viability compared to untreated alloys, which exhibited high cell viability (>100 %) after 5 days and high alkaline phosphatase activity after 7 days. Cell proliferation assays indicated that MG 63 cells grew faster on mineralized surfaces than on untreated surfaces. Scanning electron microscopy imaging confirmed that the cells adhered and spread well on mineralized surfaces. Furthermore, hemocompatibility test results revealed that all mineralized samples were non-hemolytic. Our results demonstrate the viability of employing the ELR mineralizing platform to improve alloy biocompatibility. [Abstract copyright: Copyright © 2023. Published by Elsevier B.V.