“Endogenous Melatonin Concentration Along with the Expression of Mitochondrial Regulator Genes is Elevated by the Serum Shock Process in the U87-MG Cell Line”

According to the World Health Organization, glioblastoma, also known as the fourth grade in the development of astrocytoma, is a glial tumor limited to the central nervous system with a strong ability to invade the brain parenchyma. Melatonin can be generated outside of the pineal gland tissue, according to new research. Melatonin is produced by mitochondria independently but in concert with cell demands, and it plays an important function in cell cycle and metabolism regulation. As a result, we set out to investigate the association between cell metabolism and the serum shock-induced increase in endogenous melatonin, as well as the percentage of cell proliferation.Background: Melatonin can be produced in the mitochondria organelle of glioblastoma cells without the involvement of the pineal gland, according to new research. Regarding the physiological function of melatonin secreted by the pineal gland in the regulation of rhythmicity, the goal of this study was to see if the glioblastoma cell's melatonin production ability could be influenced using a typical serum shock technique established for cellular rhythm regulator.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PPARGC1A(PGC1-α), and DNM1L(DRP1) were measured, using qRT-PCR method.Results: In comparison to the control group, serum shock treated U87-MG glioblastoma cells had higher concentrations of cellular and released endogenous melatonin (two times). At the mRNA level, we discovered considerable upregulation of mitochondrial or circadian regulator genes (TFAM, BMAL1, PPARGC1A, and DNM1L); in the shock group compared to the control group (P <0.0002). Furthermore, although the percentage of proliferative cells (Brdu positive) was higher in the shock group, it was not statistically significant.Conclusion: The serum shock procedure has a significant impact on the U87-MG cell line's cellular activity. In terms of the study's findings, it's worth noting that an increase in endogenous melatonin concentration influences several signaling pathways within the U87-MG cell line, as seen by the increased expression of candidate genes.In light of the findings of this study, it's worth noting that further research into the role of endogenous melatonin and its effects on cancer cells is critical, and that comparing the results of normal and cancer cells can reveal the hotspots of the signaling pathways involved, which could facilitate in better understanding the biology of glioblastoma.

Endogenous Melatonin Concentration Along With the Expression of Mitochondrial Regulator Genes Is Elevated by the Serum Shock Process in the U87-MG Cell Line

Glioblastoma, also known as the fourth grade in the development of astrocytoma according to the World Health Organization, is a tumor in the glial region confined to the central nervous system with high invasion capability to the parenchyma of the brain. Recent findings suggest that melatonin can be synthesized outside the pineal gland tissue. Mitochondria can produce melatonin independently but in coordination with cell demands which plays a critical role in regulating the cell cycle and cell metabolism. hence, we aimed to examine the relationship between cell metabolism and the induction of endogenous melatonin increase induced by the serum shock process, then, determine the percentage of cell proliferation.Background: glioblastoma is a highly invasive tumor of glial cell of brain tissue. Recently it was reported that melatonin can be produced in mitochondria organelle of the glioblastoma cells independent to pineal gland. Regarding the physiological function of melatonin released from pineal gland in regulation of rhythmicity, here we aimed to investigate if serum shock standard protocol known for cellular rhythm regulator can change the melatonin production ability of the glioblastoma cell.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PGC-1α, and DRP1 were measured, using qRT-PCR method.Results: our findings showed increased (two times) concentration of cellular and released endogenous melatonin in the FBS shock treated U87-MG glioblastoma cells compared to the control group. we found significant up-regulation of the mitochondria or circadian regulator genes (TFAM, BMAL1, PGC-1α, and DRP1) at mRNA level; in the FBS shock group compared to the control group (P <0.0002). Moreover, the percent of proliferative cell (Brdu positive) was also elevated in FBS shock group however it was not statistically significant. Conclusion: the serum shock process has a far effect on the cellular behavior of the U87-MG cell line. regard to the results of the study, it is worth mentioning that an increase in the concentration of endogenous melatonin affects many signaling pathways within the U87-MG cell line, and the elevated expression of the candidate genes was the proof of this fact.by considering the results of this study it also should be noted that detailed investigating the role of endogenous melatonin and its effects on cancer cells is pivotal and by comparing the results of the normal cells with cancer cells we can find the hotspots of the involved signaling pathways that could help better understanding the biology of glioblastoma.

Control algorithm for an elastic-viscoplastic model to study processes of shock interaction of bodies

Introduction. In engineering practice, dynamic processes, with the help of which mechanics of interaction of machine components and structural elements are described and studied, are of great importance. These dynamic processes are the cause of large deformations leading to the destruction. The research objective is to develop a more accurate shock simulation algorithm through the controlled transformation of the mechanorheological shock process model from elasticviscous to elastic-viscoplastic.Materials and Methods. Differential equations of the model movement are proposed. The conditions for the transformation of the model during the transition from elastic to plastic deformations, from the stage of loading the model to the stage of unloading under the shock interaction with the surface, are considered. When calculating deformations, the assumption is made that elastic and plastic deformations occur simultaneously from the very onset of the impact. The model functioning method is considered in detail, the algorithm of the model operation is developed, the logic of its functioning is described in detail.Results. To study shock processes, a mechanoreological elastic-viscoplastic model was developed. An important parameter of the model is the force corresponding to the onset of plastic deformation. As a result of the research, a more perfect algorithm was created, and a new computer program was developed to study the shock process using an elasticviscoplastic model with an adjustable elastic-plastic transformation. Discussion and Conclusions. The results obtained can be used to improve the accuracy and reliability of simulation of shock processes in order to further develop the techniques for determining the physical and mechanical characteristics of materials by shock methods. Knowledge of the mechanical characteristics of materials is required when solving various research problems through mathematical modeling of vibration and shock processes. At the same time, an important task is to adapt the design model to the real shock process, for which it is required to develop appropriate methods and techniques.

An Estimated Search and Matching Model of the Croatian Labor Market: Post-crisis Analysis

The paper specifies a simple search and matching model of the labor market and studies how well the model can describe aggregate Croatian labor market dynamics. The model developed is a discrete-time search and matching model with convex vacancy posting costs and two types of shocks: productivity and separation shocks. The model is estimated on unemployment and vacancy data during the period from 2012 to 2020 by using Bayesian methods. The model fits the data well and the estimation shows that productivity shocks are the main driving force of the fluctuations in the labor market, especially for the case of vacancies and output, while the separation shock process accounts for a large percentage of unemployment fluctuations.

Reliability modeling and analysis for systems governed by multiple competing failures processes

Due to that the operating environment is becoming more and more complex and rigorous, the multiple competing failure modes for the reliability system is much commonly seen. In order to improve the system performance, a sensor-based degradation calibration policy (SBDC policy) is presented in this paper. The model considers the competing failure process which is described by the soft and hard failure modes. In detail, the soft failures occur when the degradation of the system exceeds the failure threshold, and the hard failures are caused by the same shock process. We use the Wiener process model to describe the soft failure and the shock process to describe the catastrophic failure. Meanwhile, in the shock process, the damage associated with the system is normal distributed which is related to the duration of the adjacent shocks. This extended model with calibrations has a good application value for the corresponding complex reliability systems which are subject to the dependent competing failure modes. By the model in this article, the system reliability and safety can be improved and the risk of the abrupt damage shall be reduced as the circumstance changes.

Fatigue Property Test and Numerical Simulation Analysis of 2524 Aluminum Alloy by Laser Shock Process

Effects of laser shock peening on the fatigue properties of 2524 aluminum alloy were investigated by laser shock test, residual stress test and fatigue crack growth test respectively. The results show that the maximum residual stress is -220MPa at a distance of 1.1mm from the spot center after LSP (laser energy of 6.26J). The distribution of residual stress was simulated by Abaqus software, and the numerical simulation results were in good agreement with the experimental results. Compared with the untreated specimens, the fatigue life of the shocked specimens was increased by 32%. Fatigue fracture morphologies of the final rupture zone also show that more dimples of significantly larger depth and size occur. The fatigue life of 2524 aluminum alloy can be effectively extended by laser shock process (LSP).