Autophagy in vascular endothelial cells Jiang, Fan
Clinical and experimental pharmacology & physiology,
November 2016, Letnik:
43, Številka:
11
Journal Article
Recenzirano
Summary
The importance of autophagy in cardiovascular physiology and cardiovascular disease is increasingly recognized; however, the precise biological effects and underlying mechanisms of autophagy ...in the cardiovascular system are still poorly understood. In the last few years, the effects of autophagy in endothelial cells have attracted great interests. This article provides a summary of our current knowledge on the regulatory factors, signalling mechanisms, and functional outcomes of autophagy in endothelial cells. It is suggested that in most situations, induction of an autophagic response has cytoprotective effects. The beneficial effects of autophagy in endothelial cells are likely to be context‐dependent, since autophagy may also contribute to cell death under certain circumstances. In addition to regulating endothelial cell survival or death, autophagy is also involved in modulating other important functions, such as nitric oxide production, angiogenesis and haemostasis/thrombosis. The mounting data will help us draw a clear picture of the roles of autophagy in endothelial cell biology and dysfunction. Given the pivotal role of endothelial dysfunction in the pathogenesis of vascular disease, disruptions of autophagy in endothelial cells are likely to have significant contributions. This is supported by some preliminary ex vivo data indicating that compromised autophagic functions may be important in the development of endothelial dysfunctions associated with diabetes and ageing.
After more than two decades of preclinical and clinical studies, on August 27, 2019, the US Food and Drug Administration (FDA) approved the adenosine A
2A
receptor antagonist Nourianz® ...(istradefylline) developed by Kyowa Hakko Kirin Inc., Japan, as an add-on treatment to levodopa in Parkinson’s disease (PD) with “OFF” episodes. This milestone achievement is the culmination of the decade-long clinical studies of the effects of istradefylline in more than 4000 PD patients. Istradefylline is the first non-dopaminergic drug approved by FDA for PD in the last two decades. This approval also provides some important lessons to be remembered, namely, concerning disease-specific adenosine signaling and targeting subpopulation of PD patients. Importantly, this approval paves the way to foster entirely novel therapeutic opportunities for adenosine A
2A
receptor antagonists, such as neuroprotection or reversal of mood and cognitive deficits in PD and other neuropsychiatric diseases.
To identify the epidemiological characteristics and transmission patterns of pediatric patients with the 2019 novel coronavirus disease (COVID-19) in China.
Nationwide case series of 2135 pediatric ...patients with COVID-19 reported to the Chinese Center for Disease Control and Prevention from January 16, 2020, to February 8, 2020, were included. The epidemic curves were constructed by key dates of disease onset and case diagnosis. Onset-to-diagnosis curves were constructed by fitting a log-normal distribution to data on both onset and diagnosis dates.
There were 728 (34.1%) laboratory-confirmed cases and 1407 (65.9%) suspected cases. The median age of all patients was 7 years (interquartile range: 2-13 years), and 1208 case patients (56.6%) were boys. More than 90% of all patients had asymptomatic, mild, or moderate cases. The median time from illness onset to diagnoses was 2 days (range: 0-42 days). There was a rapid increase of disease at the early stage of the epidemic, and then there was a gradual and steady decrease. The disease rapidly spread from Hubei province to surrounding provinces over time. More children were infected in Hubei province than any other province.
Children of all ages appeared susceptible to COVID-19, and there was no significant sex difference. Although clinical manifestations of children's COVID-19 cases were generally less severe than those of adult patients, young children, particularly infants, were vulnerable to infection. The distribution of children's COVID-19 cases varied with time and space, and most of the cases were concentrated in Hubei province and surrounding areas. Furthermore, this study provides strong evidence of human-to-human transmission.
...in addition to innovative courses for a better learning experience, promotional videos can be useful to motivate children to have a healthy lifestyle at home by increasing physical activities, ...having a balanced diet, regular sleep pattern, and good personal hygiene.8 To make these educational materials truly effective, they must be age-appropriate and attractive. Schools can actively promote a health-conscious schedule, good personal hygiene, encourage physical activities, appropriate diet, and good sleep habits, and integrate such health promotion materials into the school curriculum.3 A Chinese child studies from home during the COVID-19 outbreak Fan Jiang In the event of home confinement, parents are often the closest and best resource for children to seek help from. Good parenting skills become particularly crucial when children are confined at home. Besides monitoring child performance and behaviour, parents also need to respect their identity and needs, and they need to help children develop self-discipline skills.
Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neurodegeneration, motor impairment and non-motor symptoms. Epidemiological and ...experimental investigations into potential risk factors have firmly established that dietary factor caffeine, the most-widely consumed psychoactive substance, may exerts not only neuroprotective but a motor and non-motor (cognitive) benefits in PD. These multi-benefits of caffeine in PD are supported by convergence of epidemiological and animal evidence. At least six large prospective epidemiological studies have firmly established a relationship between increased caffeine consumption and decreased risk of developing PD. In addition, animal studies have also demonstrated that caffeine confers neuroprotection against dopaminergic neurodegeneration using PD models of mitochondrial toxins (MPTP, 6-OHDA, and rotenone) and expression of α-synuclein (α-Syn). While caffeine has complex pharmacological profiles, studies with genetic knockout mice have clearly revealed that caffeine's action is largely mediated by the brain adenosine A
receptor (A
R) and confer neuroprotection by modulating neuroinflammation and excitotoxicity and mitochondrial function. Interestingly, recent studies have highlighted emerging new mechanisms including caffeine modulation of α-Syn degradation with enhanced autophagy and caffeine modulation of gut microbiota and gut-brain axis in PD models. Importantly, since the first clinical trial in 2003, United States FDA has finally approved clinical use of the A
R antagonist istradefylline for the treatment of PD with OFF-time in Sept. 2019. To realize therapeutic potential of caffeine in PD, genetic study of caffeine and risk genes in human population may identify useful pharmacogenetic markers for predicting individual responses to caffeine in PD clinical trials and thus offer a unique opportunity for "personalized medicine" in PD.
It has long been proposed that doping a chiral spin liquid (CSL) or fractional quantum Hall state can give rise to topological superconductivity. Despite intensive effort, definitive evidences still ...remain lacking. We address this problem by studying the t − J model supplemented by time-reversal symmetry breaking chiral interaction Jχon the triangular lattice using density-matrix renormalization group with a finite concentration δ of doped holes. It has been established that the undoped, i.e., δ = 0, system has a CSL ground state in the parameter region 0.32 ≤ Jχ/J ≤ 0.56. Upon light doping, we find that the ground state of the system is consistent with a Luther-Emery liquid with power-law superconducting and charge-density-wave correlations but short-range spin-spin correlations. In particular, the superconducting correlations, whose pairing symmetry is consistent with d ± id wave, are dominant at all hole doping concentrations. Our results provide direct evidences that doping the CSL on the triangular lattice can naturally give rise to topological superconductivity.
Abstract
We study the ground state properties of the Hubbard model on three-leg triangular cylinders using large-scale density-matrix renormalization group simulations. At half-filling, we identify ...an intermediate gapless spin liquid phase, which has one gapless spin mode and algebraic spin–spin correlations but exponential decay scalar chiral–chiral correlations, between a metallic phase at weak coupling and Mott insulating dimer phase at strong interaction. Upon light doping the gapless spin liquid, the system exhibits power-law charge-density-wave (CDW) correlations but short-range single-particle, spin–spin, and chiral–chiral correlations. Similar to CDW correlations, the superconducting correlations also decay in power-law but oscillate in sign as a function of distance, which is consistent with the striped pair-density wave. When further doping the gapless spin liquid phase or doping the dimer order phase, another phase takes over, which has similar CDW correlations but all other correlations decay exponentially.
A unified theory of quantum critical points beyond the conventional Landau-Ginzburg-Wilson paradigm remains unknown. According to Landau cubic criterion, phase transitions should be first-order when ...cubic terms of order parameters are allowed by symmetry in the Landau-Ginzburg free energy. Here, from renormalization group analysis, we show that second-order quantum phase transitions can occur at such putatively first-order transitions in interacting two-dimensional Dirac semimetals. As such type of Landau-forbidden quantum critical points are induced by gapless fermions, we call them fermion-induced quantum critical points. We further introduce a microscopic model of SU(N) fermions on the honeycomb lattice featuring a transition between Dirac semimetals and Kekule valence bond solids. Remarkably, our large-scale sign-problem-free Majorana quantum Monte Carlo simulations show convincing evidences of a fermion-induced quantum critical points for N = 2, 3, 4, 5 and 6, consistent with the renormalization group analysis. We finally discuss possible experimental realizations of the fermion-induced quantum critical points in graphene and graphene-like materials.Quantum phase transitions are governed by Landau-Ginzburg theory and the exceptions are rare. Here, Li et al. propose a type of Landau-forbidden quantum critical points induced by gapless fermions in two-dimensional Dirac semimetals.
Adenosine and adenosine receptors (ARs) are increasingly recognized as important therapeutic targets for controlling cognition under normal and disease conditions for its dual roles of ...neuromodulation as well as of homeostatic function in the brain. This chapter first presents the unique ability of adenosine, by acting on the inhibitory A1 and facilitating A2A receptor, to integrate dopamine, glutamate, and BNDF signaling and to modulate synaptic plasticity (e.g., long-term potentiation and long-term depression) in brain regions relevant to learning and memory, providing the molecular and cellular bases for adenosine receptor (AR) control of cognition. This led to the demonstration of AR modulation of social recognition memory, working memory, reference memory, reversal learning, goal-directed behavior/habit formation, Pavlovian fear conditioning, and effort-related behavior. Furthermore, human and animal studies support that AR activity can also, through cognitive enhancement and neuroprotection, reverse cognitive impairments in animal models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and schizophrenia. Lastly, epidemiological evidence indicates that regular human consumption of caffeine, the most widely used psychoactive drug and nonselective AR antagonists, is associated with the reduced cognitive decline in aging and AD patients, and with the reduced risk in developing PD. Thus, there is a convergence of the molecular studies revealing AR as molecular targets for integrating neurotransmitter signaling and controlling synaptic plasticity, with animal studies demonstrating the strong procognitive impact upon AR antagonism in normal and disease brains and with epidemiological and clinical evidences in support of caffeine and AR drugs for therapeutic modulation of cognition. Since some of adenosine A2A receptor antagonists are already in phase III clinical trials for motor benefits in PD patients with remarkable safety profiles, additional animal and human studies to better understand the mechanism underlying the AR-mediated control of cognition under normal and disease conditions will provide the required rationale to stimulate the necessary clinical investigation to rapidly translate adenosine and AR drug as a novel strategy to control memory impairment in neuropsychiatric disorders.
Sleep and Early Brain Development Jiang, Fan
Annals of nutrition & metabolism,
01/2019, Letnik:
75, Številka:
Suppl 1
Journal Article
Recenzirano
Odprti dostop
The early years of life are characterized by dramatic developmental changes. Within this important time period lies the transition from newborn to childhood. Sleep is one of the primary activities of ...the brain during early development and plays an important role in healthy cognitive and psychosocial development in early life. This paper will first review the normal sleep characteristics and their development in neonates and children, including architecture of sleep, development of a healthy sleep rhythm in early childhood, sleep recommendations and cultural disparity, as well as important factors for establishing a healthy sleep pattern during the first years of life, such as regular and consistent bedtime routine, safe and comfortable sleep environment, and appropriate sleep onset associations. This paper then provides recent updates of evidence of the effects of sleep on early brain development, particularly on learning and memory, emotional regulation, and general cognitive development through behavioral and neurophysiological studies. As regards the mechanism, many experimental sleep deprivation studies in animals and adults have attempted to explain the underlying mechanisms of sleep on cognition and the emotional brain. Future studies are expected to delineate the effects of sleep on brain structural and functional networks in the developing brain with the marked development of image acquisition approaches and the novel analysis tools for infants and young children in recent years.
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