scholarly journals Programmable Modulation for Extracellular Vesicles

2019 ◽  
Author(s):  
Yihua Wang ◽  
Richard Melvin ◽  
Lynne T. Bemis ◽  
Gregory A. Worrell ◽  
Hai-Long Wang
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Physical Method ◽  
Surface Proteins ◽  
Stimulation Parameters ◽  
Wide Range ◽  
Novel Method ◽  
Rat Astrocytes

AbstractEvery living cell releases extracellular vesicles (EVs) that are critical for cellular signaling and a wide range of biological functions. The potential diagnostic and therapeutic applications of EVs are well recognized, and rapidly expanding. While a complete understanding of the molecular mechanisms underpinning EVs release remains elusive, here we demonstrate a novel method for programmable control of the release of EVs and their cargo using external electric fields. As a proof of principle, we use cultured rat astrocytes to demonstrate how the frequency of external electrical stimulation selectively modulates EV release, their surface proteins, and microRNA profiles. This method could broadly impact biological science and medical applications. First, it raises an interesting question of how endogenous electrical activity could modulate EV production. Second, it provides a novel mechanism for tuning therapeutic electrical stimulation that may be useful for treating brain disorders. Third, it provides a new way to generate EVs carrying desired cargos by tuning electrical stimulation parameters. Unlike chemical methods for creating EVs, electrical stimulation is a clean physical method with adjustable parameters including stimulation frequency, field strength and waveform morphology.

scholarly journals Enhancing osteoblast survival through pulsed electrical stimulation and implications for osseointegration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emily Pettersen ◽  
Furqan A. Shah ◽  
Max Ortiz-Catalan
Keyword(s):  
Electrical Stimulation ◽  
Peripheral Nerve ◽  
Cell Survival ◽  
Nerve Stimulation ◽  
Peripheral Nerve Stimulation ◽  
Dependent Manner ◽  
Stimulation Parameters ◽  
Wide Range ◽  
The Impact

AbstractElectrical stimulation has been suggested as a means for promoting the direct structural and functional bonding of bone tissue to an artificial implant, known as osseointegration. Previous work has investigated the impact of electrical stimulation in different models, both in vitro and in vivo, using various electrode configurations for inducing an electric field with a wide range of stimulation parameters. However, there is no consensus on optimal electrode configuration nor stimulation parameters. Here, we investigated a novel approach of delivering electrical stimulation to a titanium implant using parameters clinically tested in a different application, namely peripheral nerve stimulation. We propose an in vitro model comprising of Ti6Al4V implants precultured with MC3T3-E1 preosteoblasts, stimulated for 72 h at two different pulse amplitudes (10 µA and 20 µA) and at two different frequencies (50 Hz and 100 Hz). We found that asymmetric charge-balanced pulsed electrical stimulation improved cell survival and collagen production in a dose-dependent manner. Our findings suggest that pulsed electrical stimulation with characteristics similar to peripheral nerve stimulation has the potential to improve cell survival and may provide a promising approach to improve peri-implant bone healing, particularly to neuromusculoskeletal interfaces in which implanted electrodes are readily available.

scholarly journals Promoting osseointegration with electrical stimulation: a review

2021 ◽  
Author(s):  
Emily Pettersen ◽  
Jenna Anderson ◽  
Max Ortiz-Catalan
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Meta Analysis ◽  
Implant Surface ◽  
Power Sources ◽  
Stimulation Parameters ◽  
Bone Quantity ◽  
Major Factors

<p>Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone-anchored implants, where osseointegration defines the biological bonding between an implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the implant-bone interface with electrical stimulation using various approaches such as different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in different <i>in vitro</i> and <i>in vivo</i> models. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using <i>in vitro</i> models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in <i>in vivo </i>investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.</p>

Promoting osseointegration with electrical stimulation: a review

2021 ◽  
Author(s):  
Emily Pettersen ◽  
Jenna Anderson ◽  
Max Ortiz-Catalan
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Meta Analysis ◽  
Implant Surface ◽  
Power Sources ◽  
Stimulation Parameters ◽  
Bone Quantity ◽  
Major Factors

<p>Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone-anchored implants, where osseointegration defines the biological bonding between an implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the implant-bone interface with electrical stimulation using various approaches such as different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in different <i>in vitro</i> and <i>in vivo</i> models. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using <i>in vitro</i> models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in <i>in vivo </i>investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.</p>

scholarly journals Enhancing osteoblast function through pulsed electrical stimulation: implications for peri-implant healing and osseointegration

2021 ◽  
Author(s):  
Emily Pettersen ◽  
Furqan A. Shah ◽  
Max Ortiz-Catalan
Keyword(s):  
Electrical Stimulation ◽  
Titanium Implant ◽  
Dependent Manner ◽  
Nervous Stimulation ◽  
Osteoblast Function ◽  
Stimulation Parameters ◽  
Wide Range ◽  
The Impact

Abstract Electrical stimulation has been suggested as a mean for promoting the bonding of bone tissue to an implant, known as osseointegration. Previous work has investigated the impact of electrical stimulation in different models, both in vitro and in vivo, using various electrode configurations for delivering the electric field and with a wide range of stimulation parameters. However, there is no consensus on optimal electrode configuration nor stimulation parameters. Here, we investigated a novel approach of delivering electrical stimulation to a titanium implant using parameters clinically tested in a different application, namely peripheral nerve stimulation. We propose an in vitro model comprising of Ti6Al4V implants precultured with MC3T3-E1 preosteoblasts, stimulated for 72 h at two different pulse amplitudes (10 µA and 20 µA) and at two different frequencies (50 Hz and 100 Hz). We found that pulsed electrical stimulation enhances cell viability (and/or proliferation) and collagen production in an approximately dose-dependent manner. Our findings suggest that pulsed electrical stimulation with characteristics similar to peripheral nervous stimulation has the potential to accelerate osteoblast function and may provide a promising approach to improving peri-implant bone healing, particularly to neuromusculoskeletal interfaces in which implanted electrodes are readily available.

Variable Precision Depth Encoding for 3D Range Geometry Compression

2020 ◽  
Vol 2020 (17) ◽  
pp. 34-1-34-7
Author(s):  
Matthew G. Finley ◽  
Tyler Bell
Keyword(s):  
Normal Distribution ◽  
Arbitrary Distribution ◽  
File Size ◽  
Geometry Compression ◽  
Variable Precision ◽  
Wide Range ◽  
Novel Method ◽  
Encoding Method ◽  
Rgb Image ◽  
Color Channels

This paper presents a novel method for accurately encoding 3D range geometry within the color channels of a 2D RGB image that allows the encoding frequency—and therefore the encoding precision—to be uniquely determined for each coordinate. The proposed method can thus be used to balance between encoding precision and file size by encoding geometry along a normal distribution; encoding more precisely where the density of data is high and less precisely where the density is low. Alternative distributions may be followed to produce encodings optimized for specific applications. In general, the nature of the proposed encoding method is such that the precision of each point can be freely controlled or derived from an arbitrary distribution, ideally enabling this method for use within a wide range of applications.

Expressing the Self

2018 ◽  
Keyword(s):  
Philosophy Of Mind ◽  
The Self ◽  
Epistemic Status ◽  
First Person ◽  
Semantic Categories ◽  
Wide Range ◽  
Person Reference ◽  
De Se ◽  
Novel Method ◽  
Cultural Pragmatics

This book addresses different linguistic and philosophical aspects of referring to the self in a wide range of languages from different language families, including Amharic, English, French, Japanese, Korean, Mandarin, Newari (Sino-Tibetan), Polish, Tariana (Arawak), and Thai. In the domain of speaking about oneself, languages use a myriad of expressions that cut across grammatical and semantic categories, as well as a wide variety of constructions. Languages of Southeast and East Asia famously employ a great number of terms for first-person reference to signal honorification. The number and mixed properties of these terms make them debatable candidates for pronounhood, with many grammar-driven classifications opting to classify them with nouns. Some languages make use of egophors or logophors, and many exhibit an interaction between expressing the self and expressing evidentiality qua the epistemic status of information held from the ego perspective. The volume’s focus on expressing the self, however, is not directly motivated by an interest in the grammar or lexicon, but instead stems from philosophical discussions of the special status of thoughts about oneself, known as de se thoughts. It is this interdisciplinary understanding of expressing the self that underlies this volume, comprising philosophy of mind at one end of the spectrum and cross-cultural pragmatics of self-expression at the other. This unprecedented juxtaposition results in a novel method of approaching de se and de se expressions, in which research methods from linguistics and philosophy inform each other. The importance of this interdisciplinary perspective on expressing the self cannot be overemphasized. Crucially, the volume also demonstrates that linguistic research on first-person reference makes a valuable contribution to research on the self tout court, by exploring the ways in which the self is expressed, and thereby adding to the insights gained through philosophy, psychology, and cognitive science.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals Single Step In Situ Detection of Surface Protein and MicroRNA in Clustered Extracellular Vesicles Using Flow Cytometry

2021 ◽  
Vol 10 (2) ◽  
pp. 319
Author(s):  
Hee Cheol Yang ◽  
Won Jong Rhee
Keyword(s):  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Molecular Beacon ◽  
Disease Diagnosis ◽  
Single Step ◽  
Flow Cytometer ◽  
Surface Proteins ◽  
Biomarker Detection ◽  
In Situ Detection

Because cancers are heterogeneous, it is evident that multiplexed detection is required to achieve disease diagnosis with high accuracy and specificity. Extracellular vesicles (EVs) have been a subject of great interest as sources of novel biomarkers for cancer liquid biopsy. However, EVs are nano-sized particles that are difficult to handle; thus, it is necessary to develop a method that enables efficient and straightforward EV biomarker detection. In the present study, we developed a method for single step in situ detection of EV surface proteins and inner miRNAs simultaneously using a flow cytometer. CD63 antibody and molecular beacon-21 were investigated for multiplexed biomarker detection in normal and cancer EVs. A phospholipid-polymer-phospholipid conjugate was introduced to induce clustering of the EVs analyzed using nanoparticle tracking analysis, which enhanced the detection signals. As a result, the method could detect and distinguish cancer cell-derived EVs using a flow cytometer. Thus, single step in situ detection of multiple EV biomarkers using a flow cytometer can be applied as a simple, labor- and time-saving, non-invasive liquid biopsy for the diagnosis of various diseases, including cancer.

scholarly journals Lipoproteins Are Responsible for the Pro-Inflammatory Property of Staphylococcus aureus Extracellular Vesicles

2021 ◽  
Vol 22 (13) ◽  
pp. 7099
Author(s):  
Pradeep Kumar Kopparapu ◽  
Meghshree Deshmukh ◽  
Zhicheng Hu ◽  
Majd Mohammad ◽  
Marco Maugeri ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Responses ◽  
Surface Proteins ◽  
Host Cells ◽  
Immune Stimulation ◽  
Domains Of Life ◽  
Major Surface ◽  
Staphylococcal Aureus

Staphylococcal aureus (S. aureus), a Gram-positive bacteria, is known to cause various infections. Extracellular vesicles (EVs) are a heterogeneous array of membranous structures secreted by cells from all three domains of life, i.e., eukaryotes, bacteria, and archaea. Bacterial EVs are implied to be involved in both bacteria–bacteria and bacteria–host interactions during infections. It is still unclear how S. aureus EVs interact with host cells and induce inflammatory responses. In this study, EVs were isolated from S. aureus and mutant strains deficient in either prelipoprotein lipidation (Δlgt) or major surface proteins (ΔsrtAB). Their immunostimulatory capacities were assessed both in vitro and in vivo. We found that S. aureus EVs induced pro-inflammatory responses both in vitro and in vivo. However, this activity was dependent on lipidated lipoproteins (Lpp), since EVs isolated from the Δlgt showed no stimulation. On the other hand, EVs isolated from the ΔsrtAB mutant showed full immune stimulation, indicating the cell wall anchoring of surface proteins did not play a role in immune stimulation. The immune stimulation of S. aureus EVs was mediated mainly by monocytes/macrophages and was TLR2 dependent. In this study, we demonstrated that not only free Lpp but also EV-imbedded Lpp had high pro-inflammatory activity.

scholarly journals Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Aurora Kinase ◽  
Interacting Proteins ◽  
Multiple Tumor ◽  
Oncogenic Pathways ◽  
Wide Range ◽  
The Family ◽  
Tumor Types ◽  
Cancer Tissues

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

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