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1.
Ageing Res Rev ; 95: 102223, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38325753

ABSTRACT

Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive cognitive decline and the accumulation of amyloid-beta plaques, tau tangles, and neuroinflammation in the brain. Postoperative cognitive dysfunction (POCD) is a prevalent and debilitating condition characterized by cognitive decline following neuroinflammation and oxidative stress induced by procedures. POCD and AD are two conditions that share similarities in the underlying mechanisms and pathophysiology. Compared to normal aging individuals, individuals with POCD are at a higher risk for developing AD. Emerging evidence suggests that astrocytes, the most abundant glial cells in the central nervous system, play a critical role in the pathogenesis of these conditions. Comprehensive functions of astrocyte in AD has been extensively explored, but very little is known about POCD may experience late-onset AD pathogenesis. Herein, in this context, we mainly explore the multifaceted roles of astrocytes in the context of POCD, highlighting their involvement in neuroinflammation, neurotransmitter regulation, synaptic plasticity and neurotrophic support, and discuss how POCD may augment the onset of AD. Additionally, we discuss potential therapeutic strategies targeting astrocytes to mitigate or prevent POCD, which hold promise for improving the quality of life for patients undergoing surgeries and against AD in the future.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Postoperative Cognitive Complications , Humans , Astrocytes/pathology , Postoperative Cognitive Complications/pathology , Neuroinflammatory Diseases , Quality of Life , Alzheimer Disease/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathology , Amyloid beta-Peptides
2.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 166992, 2024 03.
Article in English | MEDLINE | ID: mdl-38128844

ABSTRACT

Traumatic brain injury (TBI), a significant contributor to mortality and morbidity worldwide, is a devastating condition characterized by initial mechanical damage followed by subsequent biochemical processes, including neuroinflammation. Astrocytes, the predominant glial cells in the central nervous system, play a vital role in maintaining brain homeostasis and supporting neuronal function. Nevertheless, in response to TBI, astrocytes undergo substantial phenotypic alternations and actively contribute to the neuroinflammatory response. This article explores the multifaceted involvement of astrocytes in neuroinflammation subsequent to TBI, with a particular emphasis on their activation, release of inflammatory mediators, modulation of the blood-brain barrier, and interactions with other immune cells. A comprehensive understanding the dynamic interplay between astrocytes and neuroinflammation in the condition of TBI can provide valuable insights into the development of innovative therapeutic approaches aimed at mitigating secondary damage and fostering neuroregeneration.


Subject(s)
Astrocytes , Brain Injuries, Traumatic , Humans , Neuroinflammatory Diseases , Brain Injuries, Traumatic/complications , Brain , Inflammation/complications
3.
Front Plant Sci ; 13: 973639, 2022.
Article in English | MEDLINE | ID: mdl-36160995

ABSTRACT

Organic fertilizer is effective in improving soil quality, and promoting crop growth. Combined organic and inorganic fertilization has been proved as a more favorable way to tobacco yield and quality. However, the mechanisms underlying tobacco yield and quality under combinations of different organic and inorganic fertilizer remain unclear. We conducted a 12-year tobacco (Nicotiana tabacum L.)-maize crop rotation field experiment in Yanhe experimental station, China to examine the yields and qualities of tobacco, soil nutrients, and extracellular enzyme activities associated with carbon, nitrogen, and phosphorus cycles in response to different fertilization treatments. Five fertilization treatments (no fertilization; 75 kg N fertilizer ha-1; 450 kg oil cake ha-1 + 75 kg N fertilizer ha-1; 15,000 kg pig dung ha-1 + 60 kg N fertilizer ha-1; 3,000 kg straw ha-1 + 75 kg N fertilizer ha-1) were applied to tobacco while maize was fertilized with inorganic compound fertilizers. After 12 years of tobacco-maize rotation, the results showed that organic fertilizer additions elevate tobacco yield and quality, and the soil extracellular enzymes activities. Gram-negative bacteria, actinomycetes, and total soil microbial biomass were increased by organic fertilizer additions, both plant-based (oil cake and straw) and animal-based (pig dung) organics. The levels of soil organic matter, total organic carbon, total phosphorus and available phosphorus are higher in pig dung addition treatment than oil cake and straw additions. By variance analysis with respect to fertilization treatments, organic sources differentially affected the activities of diverse soil enzymes. The redundancy analysis gave that yield and quality of tobacco leaves (upper, middle, and lower leaves) positively related to soil extracellular enzyme activities. Based on analysis of yield and quality of tobacco leaves with extracellular enzyme activities and soil nutrients, it is suggested animal-based organic fertilizer, thus pig dung, should be used in combining with chemical fertilizers to improve the quality of tobacco and soil nutrients.

4.
J Theor Biol ; 527: 110790, 2021 10 21.
Article in English | MEDLINE | ID: mdl-34087270

ABSTRACT

Circadian clocks allow living organisms to anticipate and adapt to the daily variations of the environment. The interlocked feedback loops of the transcription factors network in the plant clock generate oscillations with expression peaks at specific times of the day. In this work, we explore the effect of molecular noise on the behavior of the plant circadian clock through numerical simulations. The influence of system size, photoperiod, and mutations of clock genes on the robustness of the oscillations are discussed. Our simulations show that the oscillations remain robust when the mRNA and protein levels are in the range of a few hundreds molecules. Entrainment by light-dark cycles enhances the robustness compared to constant conditions. Multiple light inputs and inter-cellular coupling also contribute to the robustness of the oscillations. The comparison between deterministic and stochastic simulations of single and double mutants shows that stochasticity does not qualitatively affect the behaviour of mutants but that they do not have the same robustness to noise. Finally, the model shows that noise can induce transitions between two limit cycles in a birhythmic clock mutant.


Subject(s)
Circadian Clocks , Circadian Rhythm , Circadian Clocks/genetics , Computer Simulation , Models, Biological , Photoperiod
5.
Front Physiol ; 11: 591073, 2020.
Article in English | MEDLINE | ID: mdl-33250782

ABSTRACT

Understanding the mechanism by which plants respond to cold stress and strengthen their tolerance to low temperatures is an important and challenging task in plant sciences. Experiments have established that the first step in the perception and transduction of the cold stress signal consists of a transient influx of Ca2+. This Ca2+ influx triggers the activation of a cascade of phosphorylation-dephosphorylation reactions that eventually affects the expression of C-repeat-binding factors (CBFs, notably CBF3), which were shown in many plants to control resistance to cold stress by regulating the expression of cold-regulated (COR) genes. Based on experimental observations mostly made on Arabidopsis thaliana, we build a computational model for the cold response pathway in plants, from the transduction of the cold signal via the transient influx of Ca2+ to the activation of the phosphorylation cascade leading to CBF3 expression. We explore the dynamics of this regulatory network by means of numerical simulations and compare the results with experimental observations on the dynamics of the cold response, both for the wild type and for mutants. The simulations show how, in response to cold stress, a brief Ca2+ influx, which is over in minutes, is transduced along the successive steps of the network to trigger the expression of cold response genes such as CBF3 within hours. Sometimes, instead of a single Ca2+ spike the decrease in temperature brings about a train of high-frequency Ca2+ oscillations. The model is applied to both types of Ca2+ signaling. We determine the dynamics of the network in response to a series of identical cold stresses, to account for the observation of desensitization and resensitization. The analysis of the model predicts the possibility of an oscillatory expression of CBF3 originating from the negative feedback exerted by ZAT12, a factor itself controlled by CBF3. Finally, we extend the model to incorporate the circadian control of CBF3 expression, to account for the gating of the response to cold stress by the plant circadian clock.

6.
Sci Rep ; 9(1): 19145, 2019 12 16.
Article in English | MEDLINE | ID: mdl-31844090

ABSTRACT

We investigated risk factors for postoperative serious adverse events (SAEs) in elderly patients with preoperative chronic hypoxaemia undergone total hip arthroplasty (THA) or hemiarthroplasty and performed an implementation to modify and improve clinical outcome. A retrospective medical record review was performed to identify geriatric patients who receiving THA or hemiarthroplasty at a single university teaching hospital, Kunming, Yunnan, China between January 2009 and August 2017. Total of 450 elderly patients were included in the study. Data were collected on baseline characteristics, detailed treatments, and adverse events. Univariate and multivariate logistic regression analysis were used to identify risk factors for SAEs. In multivariate regression analysis, a higher occurrence of general anaesthesia and multiple episodes of hypotension were associated with higher risk of SAEs (general anesthesia: odds ratio [OR] 5.09, 95% confidence interval [CI] 1.96-13.24, P = 0.001; hypotension time: OR 4.29, 95% CI 1.66-11.10, P = 0.003). After the multidisciplinary implementation, the postoperative length of stay was decreased from 15 days to 10 days (P < 0.0001); incidence of SAEs was decreased from 21.1% to 7.0% (P = 0.002), and the all-cause mortality rate within 30 days decreased from 4.6% to 1.0% (P = 0.040). Our observational study demonstrated that an increasing application of general anaesthesia and longer time of hypotension were associated with an increased risk of postoperative SAEs in patients after THA or hemiarthroplasty. Additionally, optimizing stable haemodynamics under higher application of combined-spinal epidural anaesthesia was associated with improved outcome up to 30 days after THA or hemiarthroplasty.


Subject(s)
Arthroplasty, Replacement, Hip , Geriatrics , Hypoxia/complications , Interdisciplinary Research , Preoperative Period , Recovery of Function , Aged , Aged, 80 and over , Chronic Disease , Female , Humans , Hypoxia/epidemiology , Incidence , Logistic Models , Male , Risk Factors
7.
Medicine (Baltimore) ; 96(15): e6587, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28403091

ABSTRACT

The partial pressure of oxygen decreases as altitude increases, the preoperative chronic hypoxemia (CH) may have a plausible clinical impact. Risk factors for postoperative serious adverse events (pSAEs) in patients living in high altitudes during primary hip arthroplasty (HA) are not clear.This is an observational study embracing patients from January 1, 2011 to December 31, 2015 at Yan'an Hospital of Kunming City, a 1338-bed municipal teaching hospital of Kunming Medical University. Univariate analysis revealed that significant differences between patients with and without preoperative CH occurred in intraoperative hypotension (77 [33%] vs 34 [47%], P = .040) and that significant differences between patients with and without pSAEs occurred in following variables: preoperative CH (32 [57%] vs 199 [80%], P < .001), intraoperative hypotension (37 [66%] vs 74 [30%], P < .001), highest noradrenaline support (.09 [.01-.21] vs .03 [.01-.05] µg/kg/min, P < .001), higher application of general anesthesia (15 [27%] vs 29 [12%], P = .004), and lower of combined-spinal epidural anesthesia (CSEA) (21 [37%] vs 165 [66%], P < .001). The general anesthesia and intraoperative hypotension remained the independent risk factors for pSAEs (P < .05), while the preoperative CH presented by decreasing its risk (P < .05).This study suggests that various intraoperative events including general anesthesia, hypotension were risk factors for the development of pSAEs. Preoperative CH, presenting with decreased incidence of intensive care unit (ICU) admission and pSAEs, may mimic hypoxic preconditioning in organic protection, for which further study is needed to uncover the underlying mechanisms.


Subject(s)
Altitude , Arthroplasty, Replacement, Hip/adverse effects , Hypoxia/complications , Intraoperative Care/adverse effects , Intraoperative Complications/etiology , Postoperative Complications/etiology , Age Factors , Aged , Aged, 80 and over , Anesthesia, Epidural/adverse effects , Anesthesia, Epidural/methods , Anesthesia, General/adverse effects , Anesthesia, Spinal/adverse effects , Anesthesia, Spinal/methods , Arthroplasty, Replacement, Hip/methods , Chronic Disease , Female , Humans , Hypotension/etiology , Intraoperative Care/methods , Male , Multivariate Analysis , Norepinephrine/administration & dosage , Partial Pressure , Preoperative Period , Retrospective Studies , Risk Factors , Treatment Outcome
8.
Comput Math Methods Med ; 2017: 2729683, 2017.
Article in English | MEDLINE | ID: mdl-28203268

ABSTRACT

A novel family of exponential Runge-Kutta (expRK) methods are designed incorporating the stable steady-state structure of genetic regulatory systems. A natural and convenient approach to constructing new expRK methods on the base of traditional RK methods is provided. In the numerical integration of the one-gene, two-gene, and p53-mdm2 regulatory systems, the new expRK methods are shown to be more accurate than their prototype RK methods. Moreover, for nonstiff genetic regulatory systems, the expRK methods are more efficient than some traditional exponential RK integrators in the scientific literature.


Subject(s)
Gene Regulatory Networks , Proto-Oncogene Proteins c-mdm2/genetics , Tumor Suppressor Protein p53/genetics , Algorithms , Computational Biology/methods , Computer Simulation , Humans , Models, Genetic , Numerical Analysis, Computer-Assisted , Protein Biosynthesis , RNA, Messenger/metabolism , Systems Biology , Transcription, Genetic
9.
Comput Math Methods Med ; 2015: 689137, 2015.
Article in English | MEDLINE | ID: mdl-26633991

ABSTRACT

Oscillation is one of the most important phenomena in the chemical reaction systems in living cells. The general purpose simulation algorithms fail to take into account this special character and produce unsatisfying results. In order to enhance the accuracy of the integrator, the second-order derivative is incorporated in the scheme. The oscillatory feature of the solution is captured by the integrators with an exponential fitting property. Three practical exponentially fitted TDRK (EFTDRK) methods are derived. To test the effectiveness of the new EFTDRK methods, the two-gene system with cross-regulation and the circadian oscillation of the period protein in Drosophila are simulated. Each EFTDRK method has the best fitting frequency which minimizes the global error. The numerical results show that the new EFTDRK methods are more accurate and more efficient than their prototype TDRK methods or RK methods of the same order and the traditional exponentially fitted RK method in the literature.


Subject(s)
Gene Regulatory Networks , Models, Genetic , Algorithms , Animals , Computational Biology/methods , Computer Simulation , Drosophila/genetics , Drosophila Proteins/genetics , Period Circadian Proteins/genetics
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