scholarly journals Detection of Alzheimer's associated microRNAs using a DNA-based smart reagent

2021 ◽  
Author(s):  
Arun Richard Chandrasekaran ◽  
Ken Halvorsen
Keyword(s):  
Biomarker Discovery ◽  
Neurodegenerative Disorder ◽  
Single Step ◽  
Proof Of Concept ◽  
Concept Detection ◽  
Microrna Family ◽  
Significant Research ◽  
New Biomarkers ◽  
Clinical Potential

Alzheimer's disease (AD) is the most common neurodegenerative disorder, with significant research efforts devoted to identifying new biomarkers for clinical diagnosis and treatment. MicroRNAs have emerged as likely disease regulators and biomarkers for AD, now implicated as having roles in several biological processes related to progression of the disease. In this work, we use the miRacles assay (microRNA activated conditional looping of engineered switches) for single-step detection of AD-related microRNAs. The technology is based on conformationally responsive DNA nanoswitches that loop upon recognition of a target microRNA and report their on/off status through an electrophoretic readout. Unlike many other methods, our approach directly detects native microRNAs without amplification or labeling, eliminating the need for expensive enzymes, reagents, and equipment. We used this assay to screen for AD-related microRNAs, demonstrate specificity within a microRNA family, sensitivity of ~ 8 fM, and multiplexing capability to simultaneously detect four microRNA targets. Toward clinical use, we provide proof-of-concept detection and quantifiable dysregulation of specific microRNAs from total RNA extracts derived from healthy and AD brain samples. In the context of AD, this "smart reagent" could facilitate biomarker discovery, accelerate efforts to understand the role of microRNAs in AD, and have clinical potential as a diagnostic or monitoring tool for validated biomarkers.

scholarly journals Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1353
Author(s):  
Francesca Romana Buccellato ◽  
Marianna D’Anca ◽  
Chiara Fenoglio ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Damage ◽  
Molecular Mechanisms ◽  
Biomarker Discovery ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Antioxidant Defenses ◽  
Ageing Population

Alzheimer’s disease (AD) is a neurodegenerative disorder accounting for over 50% of all dementia patients and representing a leading cause of death worldwide for the global ageing population. The lack of effective treatments for overt AD urges the discovery of biomarkers for early diagnosis, i.e., in subjects with mild cognitive impairment (MCI) or prodromal AD. The brain is exposed to oxidative stress as levels of reactive oxygen species (ROS) are increased, whereas cellular antioxidant defenses are decreased. Increased ROS levels can damage cellular structures or molecules, leading to protein, lipid, DNA, or RNA oxidation. Oxidative damage is involved in the molecular mechanisms which link the accumulation of amyloid-β and neurofibrillary tangles, containing hyperphosphorylated tau, to microglia response. In this scenario, microglia are thought to play a crucial role not only in the early events of AD pathogenesis but also in the progression of the disease. This review will focus on oxidative damage products as possible peripheral biomarkers in AD and in the preclinical phases of the disease. Particular attention will be paid to biological fluids such as blood, CSF, urine, and saliva, and potential future use of molecules contained in such body fluids for early differential diagnosis and monitoring the disease course. We will also review the role of oxidative damage and microglia in the pathogenesis of AD and, more broadly, in neurodegeneration.

Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease

2019 ◽  
Vol 26 (20) ◽  
pp. 3719-3753 ◽  
Author(s):  
Natasa Kustrimovic ◽  
Franca Marino ◽  
Marco Cosentino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Neurodegenerative Process ◽  
Progressive Degeneration ◽  
Cytokine Levels ◽  
Inflammatory Phenotype ◽  
Immune Challenges

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

Microglia in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Patrick Süß ◽  
Johannes C.M. Schlachetzki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
Disease Stage ◽  
Disease Modifying Therapy ◽  
Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

scholarly journals Utilizing the Food–Pathogen Metabolome to Putatively Identify Biomarkers for the Detection of Shiga Toxin-Producing E. coli (STEC) from Spinach

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 67
Author(s):  
Snehal R. Jadhav ◽  
Rohan M. Shah ◽  
Avinash V. Karpe ◽  
Robert S. Barlow ◽  
Kate E. McMillan ◽  
...  
Keyword(s):  
Shiga Toxin ◽  
Metabolic Profiling ◽  
Biomarker Discovery ◽  
Risk Groups ◽  
Proof Of Concept ◽  
Rapid Methods ◽  
E Coli ◽  
Leafy Greens ◽  
Food Pathogen ◽  
Genomic Similarity

Shiga toxigenic E. coli (STEC) are an important cause of foodborne disease globally with many outbreaks linked to the consumption of contaminated foods such as leafy greens. Existing methods for STEC detection and isolation are time-consuming. Rapid methods may assist in preventing contaminated products from reaching consumers. This proof-of-concept study aimed to determine if a metabolomics approach could be used to detect STEC contamination in spinach. Using untargeted metabolic profiling, the bacterial pellets and supernatants arising from bacterial and inoculated spinach enrichments were investigated for the presence of unique metabolites that enabled categorization of three E. coli risk groups. A total of 109 and 471 metabolite features were identified in bacterial and inoculated spinach enrichments, respectively. Supervised OPLS-DA analysis demonstrated clear discrimination between bacterial enrichments containing different risk groups. Further analysis of the spinach enrichments determined that pathogen risk groups 1 and 2 could be easily discriminated from the other groups, though some clustering of risk groups 1 and 2 was observed, likely representing their genomic similarity. Biomarker discovery identified metabolites that were significantly associated with risk groups and may be appropriate targets for potential biosensor development. This study has confirmed that metabolomics can be used to identify the presence of pathogenic E. coli likely to be implicated in human disease.

scholarly journals The role of epigenetic modifications for the pathogenesis of Crohn's disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Biomarkers ◽  
Insight Into ◽  
Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

scholarly journals Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1443
Author(s):  
Leonie D. H. Gossel ◽  
Catrin Heim ◽  
Lisa-Marie Pfeffermann ◽  
Laura M. Moser ◽  
Halvard B. Bönig ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Cells ◽  
Chimeric Antigen Receptor ◽  
Treatment Options ◽  
Antigen Receptor ◽  
Proof Of Concept ◽  
Cell Monolayers ◽  
Novel Treatment ◽  
Dismal Prognosis

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS.

scholarly journals The Constantly Evolving Role of Medical Image Processing in Oncology: From Traditional Medical Image Processing to Imaging Biomarkers and Radiomics

2021 ◽  
Vol 7 (8) ◽  
pp. 124
Author(s):  
Kostas Marias
Keyword(s):  
Image Processing ◽  
Image Analysis ◽  
Medical Image ◽  
Biomarker Discovery ◽  
Medical Image Processing ◽  
Machine Learning Techniques ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Precision Oncology

The role of medical image computing in oncology is growing stronger, not least due to the unprecedented advancement of computational AI techniques, providing a technological bridge between radiology and oncology, which could significantly accelerate the advancement of precision medicine throughout the cancer care continuum. Medical image processing has been an active field of research for more than three decades, focusing initially on traditional image analysis tasks such as registration segmentation, fusion, and contrast optimization. However, with the advancement of model-based medical image processing, the field of imaging biomarker discovery has focused on transforming functional imaging data into meaningful biomarkers that are able to provide insight into a tumor’s pathophysiology. More recently, the advancement of high-performance computing, in conjunction with the availability of large medical imaging datasets, has enabled the deployment of sophisticated machine learning techniques in the context of radiomics and deep learning modeling. This paper reviews and discusses the evolving role of image analysis and processing through the lens of the abovementioned developments, which hold promise for accelerating precision oncology, in the sense of improved diagnosis, prognosis, and treatment planning of cancer.

The Entrepreneurship Educator: Understanding Role Identity

2020 ◽  
pp. 251512742097966
Author(s):  
Birgitte Wraae ◽  
Candida Brush ◽  
Shahrokh Nikou
Keyword(s):  
Role Identity ◽  
Future Research ◽  
Analysis Tool ◽  
Perceptions Of Students ◽  
Significant Research ◽  
Future Research Directions ◽  
The Relationship ◽  
Role Identity Theory ◽  
Depth Interviews

Significant research explores effectiveness of entrepreneurial curriculum, teaching innovations and programs, but less often studied is the role of entrepreneurship educators. The way that the educator sees his or her role relative to the students is of critical importance because this directly influences pedagogy choices, expectations for students and learning outcomes, as well as job satisfaction. While recent studies propose typologies characterizing pedagogical approaches of educators, few of these are based on the data from entrepreneurship educators. Framed within role identity theory, we conducted 13 in–depth interviews to examine how entrepreneurship educators perceive their role. Using the qualitative data analysis tool (NVivo), we analyzed how the relationship between their perceptions of their role and core value orientation is connected to teaching approaches. Results show that these educators view their roles as teacher-focused, network-focused, or student-focused and that these perspectives are associated with different perceptions of students’ role and learning objectives. Further, we find different levels of emphasis on roles and that personal core values are differentially linked to these roles. Implications and future research directions are discussed.

scholarly journals Improving Equine Welfare through Human Habit Formation

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2156
Author(s):  
Jo White ◽  
Ruth Sims
Keyword(s):  
Management Practices ◽  
Habit Formation ◽  
Positive Impact ◽  
Proof Of Concept ◽  
Mutual Benefit ◽  
Structured Interviews ◽  
Behavioural Research ◽  
Equine Welfare ◽  
Lasting Change

This paper explores the potential for interventions to develop pro-animal welfare habitual behaviours (PAWHBs) in people to improve the lives of animals. Human behavioural research indicates that opportunities exist to deliver lasting change through developing positive habitual behaviours. The routine nature of many equine care and management practices lends itself to habit formation and maintenance. This proof-of-concept paper aims to evaluate a theory-based intervention of developing and maintaining a PAWHB in people caring for equines. Qualitative research methods were used. A 30 day PAWHB intervention (PAWHBInt) of providing enrichment to an equine by scratching them in a consistent context linked to an existing routine behaviour was undertaken. Participants (n = 9) then engaged in semi-structured interviews that were analysed using thematic analysis, where the participants self-reported the outcomes they observed during the intervention. The study findings suggest that the PAWHBInt had a positive impact on human behaviour and habit formation. The research helps to address the dearth of evidence regarding the application of habit theory to equine welfare interventions and emphasised linking a desired new behaviour to an existing routine behaviour when developing PAWHBs. The research also highlights the role of mutual benefit for human and equine, and emotion in providing feedback and potential reward, supporting the link to the cue-routine-reward principle of habit theory.

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