scholarly journals Elevated Cerebrospinal Fluid and Plasma N-Cadherin in Alzheimer Disease

2020 ◽  
Vol 79 (5) ◽  
pp. 484-492
Author(s):  
Ji-Young Choi ◽  
Sun-Jung Cho ◽  
Jung Hyun Park ◽  
Sang-Moon Yun ◽  
Chulman Jo ◽  
...  

Abstract N-cadherin is a synaptic adhesion molecule stabilizing synaptic cell structure and function. Cleavage of N-cadherin by γ-secretase produces a C-terminal fragment, which is increased in the brains of Alzheimer disease (AD) patients. Here, we investigated the relationship between fluid N-cadherin levels and AD pathology. We first showed that the cleaved levels of N-cadherin were increased in homogenates of postmortem brain from AD patients compared with that in non-AD patients. We found that cleaved N-cadherin levels in the cerebrospinal fluid were increased in AD dementia compared with that in healthy control. ELISA results revealed that plasma levels of N-cadherin in 76 patients with AD were higher than those in 133 healthy control subjects. The N-cadherin levels in the brains of an AD mouse model, APP Swedish/PS1delE9 Tg (APP Tg) were reduced compared with that in control. The N-terminal fragment of N-cadherin produced by cleavage at a plasma membrane was detected extravascularly, accumulated in senile plaques in the cortex of an APP Tg mouse. In addition, N-cadherin plasma levels were increased in APP Tg mice. Collectively, our study suggests that alteration of N-cadherin levels might be associated with AD pathology.

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sarinnapha M. Vasunilashorn ◽  
◽  
Long H. Ngo ◽  
Simon T. Dillon ◽  
Tamara G. Fong ◽  
...  

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.


1994 ◽  
Vol 23 (2-3) ◽  
pp. 115-124 ◽  
Author(s):  
George H. Fisher ◽  
Leonard Petrucelli ◽  
Christina Gardner ◽  
Carolyn Emory ◽  
William H. Frey ◽  
...  

2018 ◽  
Author(s):  
Fu Wang ◽  
Suqin Xiong ◽  
Youping Liu ◽  
Lin Chen ◽  
Hongping Chen

Improper storage of wolfberry fruit is liable to soften, discoloration and adhesion, we call it “oil-spilling”. The purpose of the study is to explore the mechanism of “oil-spilling” of wolfberry fruits during storage. In our study, the relationship between water content, superoxide dismutase (SOD), peroxidase (POD) activity, malondialdehyde (MDA) content and the cross section, epidermal cells of wolfberry fruit were studied during storage. Results showed that wolfberry fruits began to “oil-spilling” on the 20th day, and with the extension of storage time, the degree of “oil-spilling” gradually deepened, the content of water increased and the activity of POD decreased, and the content of MDA increased. It suggested that “oil-spilling” was the result of improper external storage conditions, which it could promote the increase of water content and reactive oxygen free radical of wolfberry fruit, and lead to damage of cell structure and function and lipid peroxidation of cell membrane. The results explain the mechanism of “oil-spilling” and provide a strong basis for the establishment of scientific storage methods of wolfberry fruit.


Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1508
Author(s):  
Po-Ku Chen ◽  
Kai-Jieh Yeo ◽  
Po-Hao Huang ◽  
Shih-Hsin Chang ◽  
Ching-Kun Chang ◽  
...  

Lipid peroxidation (LPO) and hyper-ferritinemia are involved in inflammatory responses. Although hyper-ferritinemia is a characteristic of AOSD, its link to LPO remains unclear. We investigated the association between LPO and ferritin expression, and evaluated the relationship between LPO-related metabolites and inflammatory parameters. Mean fluorescence intensity (MFI) of LPO (C11-Biodipy581/591)-expressing PBMCs/monocytes in AOSD patients and healthy control (HC) subjects was determined by flow-cytometry analysis. Expression of ferritin and cytokines on PBMCs/macrophages was examined by immunoblotting. Plasma levels of LPO-related metabolites and cytokines were determined by ELISA and the MULTIPLEX platform, respectively. LPO MFI on PBMCs/monocytes were significantly higher in patients (median 4456 and 9091, respectively) compared with HC (1900, p < 0.05, and 4551, p < 0.01, respectively). Patients had higher ferritin expression on PBMCs (mean fold, 1.02) than HC (0.55, p < 0.05). Their ferritin expression levels on PBMCs stimulated with LPO inducers erastin or RSL3 (2.47 or 1.61, respectively) were higher than HC (0.84, p < 0.05, or 0.74, p < 0.01). Ferritin expression on erastin-treated/IL-1β-treated macrophages from patients were higher than those from HC (p < 0.001). The elevated levels of LPO-related metabolites, including malondialdehyde and 4-hydroxyalkenals, were positively correlated with disease activity scores, suggesting LPO involvement in AOSD pathogenesis. Increased ferritin expression on PBMCs/macrophages stimulated with LPO inducers indicates a link between LPO and elevated ferritin.


2021 ◽  
Vol 15 ◽  
Author(s):  
Xia Cao ◽  
Kevin Liu ◽  
Jun Liu ◽  
Yen-Wenn Liu ◽  
Li Xu ◽  
...  

Inflammation and the gut-brain axis have been implicated in the pathogenesis of autism spectrum disorders (ASDs). To further understand the relationship between aberrant immune responses and dysbiotic features of the gut microbiome in ASD, we enrolled 45 ASD individuals and 41 healthy control subjects with ages ranging from 2 to 19 years. We found that ASD group subjects have significantly higher plasma levels of IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, TNF-β, and IFN-γ when compared to healthy controls (FDR-adjusted p &lt; 0.05). The plasma levels of pro-inflammatory cytokines IFN-γ and IL-6 are found to be further associated with several largely pathogenic gut microbiota uniquely detected in subjects with ASD. Furthermore, the ASD gut microbiome is characterized by reduced levels of several beneficial microbiota, including Bacteroides (FDR-adjusted p &lt; 0.01) and Lachnospiraceae (FDR-adjusted p &lt; 0.001). Analysis of Lachnospiraceae family and genus level taxa suggested that relative abundances of such taxa are negatively correlated with pro-inflammatory signaling cytokines IFN-γ and IL-6, particularly in subjects with severe ASD as defined by CARS (p &lt; 0.05). Several largely pathogenic genera are determined to be associated with the pro-inflammatory cytokines IFN-γ and IL-6 (FDR-adjusted p &lt; 0.1). Additionally, IL-4 is significantly negatively correlated with CARS total score (p &lt; 0.05). Based on such results, we propose that the association between the disturbances of specific cytokines and alterations in gut microbiota abundance observed in children and adolescents with ASD provides additional evidence on the induction of aberrant pro-inflammatory mechanisms in ASD and its early diagnosis.


2009 ◽  
Vol 60-61 ◽  
pp. 27-30 ◽  
Author(s):  
Li Ping Liu ◽  
Yun Dou Wang ◽  
Yan Jun Zhang

In cell biology and medicine study, continuous high spatial resolution observations of living cells would greatly aid the elucidation of the relationship between structure and function of cells. The development of scanning probe microscopy (SPM) has opened up a new era of life science and has been used to develop a family of related methods that allow studying of cell structure and function on nanometer scale. Scanning ion conductance microscopy (SICM) is a new member of such SPM family and can be used to obtain high-resolution non-contact images of the surface of live cells under physiological conditions, and hence allows the relationship between cell microstructure and function to be probed. In this review, we concisely introduce the principles of SICM and its applications in nanobiology and nanomedicine.


Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).


Author(s):  
Nugroho Budhiwaluyo ◽  
Rayandra Asyhar ◽  
Bambang Hariyadi

  This research aims to produce a final product in the form of a performance-assessment instrument on Cell Structure and Function experiment. The development model is ADDIE. Based on expert's judgment, the instrument was valid and can be tested in the field. Field-test results shown that the product performs high validity and reliability value on measuring student performance on Cell Structure and Function experiment. Therefore, it is concluded that this performance-assessment instrument theoretically and practically has a good quality for measuring student performance in both process and product performance on Cell Structure and Function experiment. Keywords: Development, Performance-Assessment Instrument, Cell Structure and Function Experiment 


Author(s):  
J. Donald Boudreau ◽  
Eric Cassell ◽  
Abraham Fuks

This book reimagines medical education and reconstructs its design. It originates from a reappraisal of the goals of medicine and the nature of the relationship between doctor and patient. The educational blueprint outlined is called the “Physicianship Curriculum” and rests on two linchpins. First is a new definition of sickness: Patients know themselves to be ill when they cannot pursue their purposes and goals in life because of impairments in functioning. This perspective represents a bulwark against medical attention shifting from patients to diseases. The curriculum teaches about patients as functional persons, from their anatomy to their social selves, starting in the first days of the educational program and continuing throughout. Their teaching also rests on the rock-solid grounding of medicine in the sciences and scientific understandings of disease and function. The illness definition and knowledge base together create a foundation for authentic patient-centeredness. Second, the training of physicians depends on and culminates in development of a unique professional identity. This is grounded in the historical evolution of the profession, reaching back to Hippocrates. It leads to reformulation of the educational process as clinical apprenticeships and moral mentorships. “Rebirth” in the title suggests that critical ingredients of medical education have previously been articulated. The book argues that the apprenticeship model, as experienced, enriched, taught, and exemplified by William Osler, constitutes a time-honored foundation. Osler’s “natural method of teaching the subject of medicine” is a precursor to the Physicianship Curriculum.


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