scholarly journals Small Molecule Epigenetic Modulators in Pure Chemical Cell Fate Conversion

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Zhao-Di Yuan ◽  
Wei-Ning Zhu ◽  
Ke-Zhi Liu ◽  
Zhan-Peng Huang ◽  
Yan-Chuang Han
Keyword(s):  
Cell Fate ◽  
Small Molecule ◽  
Disease Modeling ◽  
Artificial Organ ◽  
Therapy Recipient ◽  
The Past ◽  
Somatic Cell Reprogramming ◽  
Cell Fate Conversion ◽  
New Strategies ◽  
Made In

Although innovative technologies for somatic cell reprogramming and transdifferentiation provide new strategies for the research of translational medicine, including disease modeling, drug screening, artificial organ development, and cell therapy, recipient safety remains a concern due to the use of exogenous transcription factors during induction. To resolve this problem, new induction approaches containing clinically applicable small molecules have been explored. Small molecule epigenetic modulators such as DNA methylation writer inhibitors, histone methylation writer inhibitors, histone acylation reader inhibitors, and histone acetylation eraser inhibitors could overcome epigenetic barriers during cell fate conversion. In the past few years, significant progress has been made in reprogramming and transdifferentiation of somatic cells with small molecule approaches. In the present review, we systematically discuss recent achievements of pure chemical reprogramming and transdifferentiation.

scholarly journals Regional specification and complementation with non-neuroectodermal cells in human brain organoids

2021 ◽  
Vol 99 (4) ◽  
pp. 489-500 ◽  
Author(s):  
Yoshiaki Tanaka ◽  
In-Hyun Park
Keyword(s):  
Endothelial Cells ◽  
Disease Modeling ◽  
Vascular Endothelial Cells ◽  
Brain Regions ◽  
Cell Reprogramming ◽  
Vascular Endothelial ◽  
The Past ◽  
Somatic Cell Reprogramming ◽  
Potential Applications ◽  
Neural Disorders

AbstractAlong with emergence of the organoids, their application in biomedical research has been currently one of the most fascinating themes. For the past few years, scientists have made significant contributions to deriving organoids representing the whole brain and specific brain regions. Coupled with somatic cell reprogramming and CRISPR/Cas9 editing, the organoid technologies were applied for disease modeling and drug screening. The methods to develop organoids further improved for rapid and efficient generation of cerebral organoids. Additionally, refining the methods to develop the regionally specified brain organoids enabled the investigation of development and interaction of the specific brain regions. Recent studies started resolving the issue in the lack of non-neuroectodermal cells in brain organoids, including vascular endothelial cells and microglia, which play fundamental roles in neurodevelopment and are involved in the pathophysiology of acute and chronic neural disorders. In this review, we highlight recent advances of neuronal organoid technologies, focusing on the region-specific brain organoids and complementation with endothelial cells and microglia, and discuss their potential applications to neuronal diseases.

scholarly journals Evolving principles underlying neural lineage conversion and their relevance for biomedical translation

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1548 ◽  
Author(s):  
Lea Jessica Flitsch ◽  
Oliver Brüstle
Keyword(s):  
Cell Fate ◽  
Disease Modeling ◽  
Direct Conversion ◽  
Neural Cells ◽  
Neural Lineage ◽  
Technological Advances ◽  
Recent Developments ◽  
Epigenetic Remodeling ◽  
Cell Fate Conversion

Scientific and technological advances of the past decade have shed light on the mechanisms underlying cell fate acquisition, including its transcriptional and epigenetic regulation during embryonic development. This knowledge has enabled us to purposefully engineer cell fates in vitro by manipulating expression levels of lineage-instructing transcription factors. Here, we review the state of the art in the cell programming field with a focus on the derivation of neural cells. We reflect on what we know about the mechanisms underlying fate changes in general and on the degree of epigenetic remodeling conveyed by the distinct reprogramming and direct conversion strategies available. Moreover, we discuss the implications of residual epigenetic memory for biomedical applications such as disease modeling and neuroregeneration. Finally, we cover recent developments approaching cell fate conversion in the living brain and define questions which need to be addressed before cell programming can become an integral part of translational medicine.

scholarly journals Genetic control of size in Drosophila

2000 ◽  
Vol 355 (1399) ◽  
pp. 945-952 ◽  
Author(s):  
Sean Oldham ◽  
Ruth Böhni ◽  
Hugo Stocker ◽  
Walter Brogiolo ◽  
Ernst Hafen
Keyword(s):  
Body Size ◽  
Genetic Control ◽  
Cell Fate ◽  
Significant Progress ◽  
The Past ◽  
Homologous Genes ◽  
Basic Body ◽  
Number Of Genes ◽  
Multicellular Organisms ◽  
Made In

During the past ten years, significant progress has been made in understanding the basic mechanisms of the development of multicellular organisms. Genetic analysis of the development of Caenorhabditis elegans and Drosophila has unearthed a fruitful number of genes involved in establishing the basic body plan, patterning of limbs, specification of cell fate and regulation of programmed cell death. The genes involved in these developmental processes have been conserved throughout evolution and homologous genes are involved in the patterning of insect and human limbs. Despite these important discoveries, we have learned astonishingly little about one of the most obvious distinctions between animals: their difference in body size. The mass of the smallest mammal, the bumble–bee bat, is 2g while that of the largest mammal, the blue whale, is 150t or 150 million grams. Remarkably, even though they are in the same class, body size can vary up to 75–million–fold. Furthermore, this body growth can be finite in the case of most vertebrates or it can occur continuously throughout life, as for trees, molluscs and large crustaceans. Currently, we know comparatively little about the genetic control of body size. In this article we will review recent evidence from vertebrates and particularly from Drosophila that implicates insulin/insulin–like growth factor–I and other growth pathways in the control of cell, organ and body size.

South Asian Developmental Crisis (Review Article)

1973 ◽  
Vol 12 (2) ◽  
pp. 181-188
Author(s):  
Rafiq Ahmad
Keyword(s):  
Second World War ◽  
World War ◽  
The Past ◽  
The Great Depression ◽  
Political Independence ◽  
Integrated Theory ◽  
Pass Through ◽  
Developed World ◽  
Second World ◽  
Made In

Like nations and civilizations, sciences also pass through period of crises when established theories are overthrown by the unpredictable behaviour of events. Economics is passing through such a crisis. The challenge thrown by the Great Depression of early 1930s took a decade before Keynes re-established the supremacy of economics. But this supremacy has again been upset by the crisis of poverty in the vast under-developed world which attained political independence after the Second World War. Poverty had always existed but never before had it been of such concern to economists as during the past twenty five years or so. Economic literature dealing with this problem has piled up but so have the agonies of poverty. No plausible and well-integrated theory of economic development or under-development has emerged so far, though brilliant advances have been made in isolated directions.

Mass Spectrometry Techniques: Principles and Practices for Quantitative Proteomics

2020 ◽  
Vol 21 ◽  
Author(s):  
Rocco J. Rotello ◽  
Timothy D. Veenstra
Keyword(s):  
Mass Spectrometry ◽  
Quantitative Proteomics ◽  
Protein Identification ◽  
Dynamic Nature ◽  
Complete Coverage ◽  
The Past ◽  
Proteome Level ◽  
A Cell ◽  
Quantitative Changes ◽  
Made In

: In the current omics-age of research, major developments have been made in technologies that attempt to survey the entire repertoire of genes, transcripts, proteins, and metabolites present within a cell. While genomics has led to a dramatic increase in our understanding of such things as disease morphology and how organisms respond to medications, it is critical to obtain information at the proteome level since proteins carry out most of the functions within the cell. The primary tool for obtaining proteome-wide information on proteins within the cell is mass spectrometry (MS). While it has historically been associated with the protein identification, developments over the past couple of decades have made MS a robust technology for protein quantitation as well. Identifying quantitative changes in proteomes is complicated by its dynamic nature and the inability of any technique to guarantee complete coverage of every protein within a proteome sample. Fortunately, the combined development of sample preparation and MS methods have made it capable to quantitatively compare many thousands of proteins obtained from cells and organisms.

Acid ceramidase, a double-edged sword in cancer aggression: A minireview

2020 ◽  
Vol 20 ◽  
Author(s):  
Helen Shiphrah Vethakanraj ◽  
Niveditha Chandrasekaran ◽  
Ashok Kumar Sekar
Keyword(s):  
Cell Fate ◽  
Cancer Progression ◽  
Potential Role ◽  
Tumour Progression ◽  
Acid Ceramidase ◽  
The Core ◽  
The Past ◽  
Sphingosine 1 Phosphate ◽  
Key Enzyme

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

Evidence-based Assessment

2010 ◽  
pp. 76-98
Author(s):  
John Hunsley ◽  
Eric J. Mash
Keyword(s):  
Decision Making ◽  
Clinical Assessment ◽  
Assessment Process ◽  
Evidence Based ◽  
The Past ◽  
Specific Assessment ◽  
The Many ◽  
Selection Of ◽  
Made In

Evidence-based assessment relies on research and theory to inform the selection of constructs to be assessed for a specific assessment purpose, the methods and measures to be used in the assessment, and the manner in which the assessment process unfolds. An evidence-based approach to clinical assessment necessitates the recognition that, even when evidence-based instruments are used, the assessment process is a decision-making task in which hypotheses must be iteratively formulated and tested. In this chapter, we review (a) the progress that has been made in developing an evidence-based approach to clinical assessment in the past decade and (b) the many challenges that lie ahead if clinical assessment is to be truly evidence-based.

scholarly journals Small Molecule Inhibitors of Influenza Virus Entry

2021 ◽  
Vol 14 (6) ◽  
pp. 587
Author(s):  
Zhaoyu Chen ◽  
Qinghua Cui ◽  
Michael Caffrey ◽  
Lijun Rong ◽  
Ruikun Du
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Virus Entry ◽  
Critical Role ◽  
Structural Basis ◽  
Future Directions ◽  
The Past

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.

The Role of Histones and Heparin in Sepsis: A Review

2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li
Keyword(s):  
Septic Shock ◽  
Multiple Organ ◽  
Clinical Settings ◽  
The Past ◽  
Life Saving ◽  
Extracellular Histones ◽  
Sepsis And Septic Shock ◽  
Development And Management ◽  
Made In

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

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