scholarly journals Clarifying mid-brain organoids: Application of the CLARITY protocol to unperfusable samples

2020 ◽  
Author(s):  
Chiara Magliaro ◽  
Arti Ahluwalia
Keyword(s):  
Pluripotent Stem Cells ◽  
3D Imaging ◽  
Imaging Techniques ◽  
Future Research ◽  
Specific Data ◽  
Promising Tool ◽  
Functional Features ◽  
Human Brains ◽  
Human Specific

The aim of this study was to apply a workflow, integrating delipidation methods and advanced 3D imaging techniques for mapping of the global neuronal organization of brain organoids. These are self-organizing constructs in vitro generated from human pluripotent stem cells encased in a Matrigel shell, which resemble downscaled structural and functional features of human brains. In particular, we focused on midbrain organoids, widely considered a promising tool for studying dopaminergic neuron degeneration in Parkinson’s Disease. The evaluation of the microanatomical alterations at a patient-level will potentially guide future research of this neuropathy, providing meaningful human specific data in line with the European Directives and the 3Rs principles.

scholarly journals Endometriosis Associated Infertility: A Critical Review and Analysis on Etiopathogenesis and Therapeutic Approaches

Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 460
Author(s):  
Lidia Filip ◽  
Florentina Duică ◽  
Alina Prădatu ◽  
Dragoș Crețoiu ◽  
Nicolae Suciu ◽  
...  
Keyword(s):  
Intrauterine Insemination ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Follicular Development ◽  
Future Research ◽  
Genetic Profile ◽  
Vitro Fertilization ◽  
Emerging Therapies ◽  
Treatment Alternatives

Endometriosis represents a frequently diagnosed gynecological affliction in the reproductive timespan of women, defined by symptoms ranging from pelvic pain to infertility. A complex interplay between the genetic profile, hormonal activity, menstrual cyclicity, inflammation status, and immunological factors define the phenotypic presentation of endometriosis. To date, imaging techniques represent the gold standard in diagnosing endometriosis, of which transvaginal ultrasonography and magnetic resonance imaging bring the most value to the diagnostic step. Current medical treatment options for endometriosis-associated infertility focus on either stimulating the follicular development and ovulation or on inhibiting the growth and development of endometriotic lesions. Techniques of assisted reproduction consisting of superovulation with in vitro fertilization or intrauterine insemination represent effective treatment alternatives that improve fertility in patients suffering from endometriosis. Emerging therapies such as the usage of antioxidant molecules and stem cells still need future research to prove the therapeutic efficacy in this pathology.

From the Inside Out: Practical Application of 3D Imaging Techniques in Art Conservation

2018 ◽  
Vol 2018 (1) ◽  
pp. 151-156
Author(s):  
Scott Geffert ◽  
Daniel Hausdorf ◽  
Joseph Coscia ◽  
Oi-Cheong Lee ◽  
Dahee Han ◽  
...  
Keyword(s):  
3D Imaging ◽  
Imaging Techniques ◽  
Art Conservation ◽  
Practical Application ◽  
Inside Out ◽  
3D Imaging Techniques

Novel Toxin-antitoxin System Xn-mazEF from Xenorhabdus nematophi-la: Identification, Characterization and Functional Exploration

2020 ◽  
Vol 16 ◽  
Author(s):  
Jogendra Singh Nim ◽  
Mohit Yadav ◽  
Lalit Kumar Gautam ◽  
Chaitali Ghosh ◽  
Shakti Sahi ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Functional Characterization ◽  
Host Cells ◽  
System Control ◽  
Xenorhabdus Nematophila ◽  
Functional Features ◽  
Dynamics Simulations ◽  
Species Specific ◽  
Rna Interaction

Background: Xenorhabdus nematophila maintains species-specific mutual interaction with nematodes of Steinernema genus. Type II Toxin Antitoxin (TA) systems, the mazEF TA system controls stress and programmed cell death in bacteria. Objective: This study elucidates the functional characterization of Xn-mazEF, a mazEF homolog in X. nematophila by computational and in vitro approaches. Methods: 3 D- structural models for Xn-MazE toxin and Xn-MazF antitoxin were generated, validated and characterized for protein - RNA interaction analysis. Further biological and cellular functions of Xn-MazF toxin were also predicted. Molecular dynamics simulations of 50ns for Xn-MazF toxin complexed with nucleic acid units (DU, RU, RC, and RU) were performed. The MazF toxin and complete MazEF operon were endogenously expressed and monitored for the killing of Escherichia coli host cells under arabinose induced tightly regulated system. Results: Upon induction, E. coli expressing toxin showed rapid killing within four hours and attained up to 65% growth inhibition, while the expression of the entire operon did not show significant killing. The observation suggests that the Xn-mazEF TA system control transcriptional regulation in X. nematophila and helps to manage stress or cause toxicity leading to programmed death of cells. Conclusion: The study provides insights into structural and functional features of novel toxin, XnMazF and provides an initial inference on control of X. nematophila growth regulated by TA systems.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

2020 ◽  
Vol 18 ◽  
Author(s):  
Debadash Panigrahi ◽  
Ganesh Prasad Mishra
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Data Bank ◽  
Future Research ◽  
Reference Compound ◽  
Unexpected Death ◽  
Main Protease ◽  
In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

scholarly journals Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

Biosensors ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 110 ◽  
Author(s):  
Erika Ferrari ◽  
Cecilia Palma ◽  
Simone Vesentini ◽  
Paola Occhetta ◽  
Marco Rasponi
Keyword(s):  
Imaging Techniques ◽  
Biological Models ◽  
Electromechanical Properties ◽  
Human Organs ◽  
Tissue Constructs ◽  
Microphysiological Systems ◽  
Metabolic Activities ◽  
On Chip ◽  
Chip Analysis

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

scholarly journals Detecting apoptosis as a clinical endpoint for proof of a clinical principle

2020 ◽  
Author(s):  
Piero Zollet ◽  
Timothy E.Yap ◽  
M Francesca Cordeiro
Keyword(s):  
Drug Development ◽  
Therapeutic Response ◽  
Imaging Techniques ◽  
Brain Diseases ◽  
Promising Strategy ◽  
Sight Loss ◽  
Apoptosis Detection ◽  
Novel Therapeutic Strategies

The transparent eye media represent a window through which to observe changes occurring in the retina during pathological processes. In contrast to visualising the extent of neurodegenerative damage that has already occurred, imaging an active process such as apoptosis has the potential to report on disease progression and therefore the threat of irreversible functional loss in various eye and brain diseases. Early diagnosis in these conditions is an important unmet clinical need to avoid or delay irreversible sight loss. In this setting, apoptosis detection is a promising strategy with which to diagnose, provide prognosis, and monitor therapeutic response. Additionally, monitoring apoptosis in vitro and in vivo has been shown to be valuable for drug development in order to assess the efficacy of novel therapeutic strategies both in the pre-clinical and clinical setting. Detection of Apoptosing Retinal Cells (DARC) technology is to date the only tool of its kind to have been tested in clinical trials, with other new imaging techniques under investigation in the fields of neuroscience, ophthalmology and drug development. We summarize the transitioning of techniques detecting apoptosis from bench to bedside, along with the future possibilities they encase.

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