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Topic Review
MRGPRX2
Mas-related G-protein coupled receptor member X2 (MRGPRX2) is a class A GPCR expressed on mast cells. Mast cells are granulated tissue-resident cells known for host cell response, allergic response, and vascular homeostasis.
  • 673
  • 22 Sep 2021
Topic Review
Suture Mesenchymal Stem Cells
Suture mesenchymal stem cells (SuSCs), a heterogeneous stem cell population, belong to mesenchymal stem cells (MSCs) or skeletal stem cells (SSCs), with the ability to self-renew and undergo multi-lineage differentiation. Unlike the well-established perivascular niche of SSCs in the long bone, stem cells of the cranial bone are generally located and confined within the cranial suture mesenchyme, subsequently defined as SuSCs. In the long bone, SSCs play an essential role in plenty of physiological processes, such as growth and development, life-long homeostasis, and fracture healing. Similarly, as the major stem cell population of cranial bones, the physiological significance of SuSCs is undoubted and self-evident. 
  • 1.5K
  • 22 Sep 2021
Topic Review
Multilayer Mesenchymal Stem Cell Sheets
Cell and gene therapies have been developing dramatically over the past decade. To face and adapt to the development of these new therapies, the Food and Drug Administration (FDA) wrote and updated new guidelines from 2016 and keep updating them. Mesenchymal stem cells (MSCs) are the most used cells for treatment, far ahead from the induced pluripotent stem cells (iPSCs), based on registered clinical trials at clinicaltrials.gov. They are widely used because of their differentiation capacity and their anti-inflammatory properties, but some controversies still require clear answers. Additional studies are needed to determine the dosage, the number, and the route of injections (location and transplantation method), and if allogenic MSCs are safe compared to autologous MSC injection, including their long-term effect. In this review, we summarized the research our company is conducting with the adipose stromal cells in engineering cell sheets and their potential application
  • 462
  • 22 Sep 2021
Topic Review
Islets of Langerhans
Islets of Langerhan are a crucial group of cells that enable the metabolization, physiologic control, and utilization of glucose, the primary energy source for cells. In situ physiologic intraportal hormone delivery from the pancreatic islets of Langerhans maintains basal normoglycemia with insulin and counterbalances hypoglycemia with glucagon. Insulin output can increase up ten-fold after a meal, and return rapidly to basal levels with no hysteresis. Type 1 diabetes represents an increasing and growingly financially unsustainable disease occurring due to the destruction of pancreatic islets of Langerhans. Current injectable insulin technologies fail to recreate physiologic glycemic control that is managed by islet cells resulting in a tight 1–2 mmol/L glycemic variance. In our opinion, exogenous subcutaneous insulin delivery, even when provided by the most ideal closed loop systems, cannot recreate this degree of dynamic control. Current therapies fail to adequately achieve euglycemia, leading to significant diabetes complications and a risk of mortality. Thus, developing a cell-based cure for type 1 diabetes through islet cell generation and transplantation remains an ideal to strive for. Achieving this goal, especially with stem cell therapies, as demonstrated by the Edmonton protocol (Shapiro 2000), demands complete understanding of embryological differentiation and physiology of the islets of Langerhans.
  • 946
  • 22 Sep 2021
Topic Review
Ink4a/Arf Expression in Pancreatic Progenitor
The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodelling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a/Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus’ expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. 
  • 537
  • 22 Sep 2021
Topic Review
Germ Cell Derivation from PSCs
Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive azoospermia (NOA) and oocyte maturation failure syndrome. In vitro gametogenesis is a promising technology to overcome infertility, particularly germ cell aplasia. Early germ cells, such as primordial germ cells, can be relatively easily derived from pluripotent stem cells (PSCs); however, further progression to post-meiotic germ cells usually requires a gonadal niche and signals from gonadal somatic cells.
  • 456
  • 22 Sep 2021
Topic Review
Flipons and Condensates Enhances Evolution
A number of insights derive from viewing flipons as scaffolds for condensates. Flipons provide a controlled way to initiate condensate formation, one subject to natural selection. The alternative conformation localizes required factors needed to regulate transcription, RNA processing, and epigenetic modification, while excluding nucleosomes and other B-DNA- and A-RNA-specific proteins that produce competing outcomes.
  • 586
  • 22 Sep 2021
Topic Review
3C Protease as Ferroptosis Inducer
Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. In the current topic the results of the study where 3Cpro-induced cell death was characterized morphologically and biochemically are presented. It was found that dead cells demonstrated necrosis-like morphological changes including permeabilization of plasma membrane, loss of mitochondrial potential, as well as mitochondria and nuclei swelling. Additionally, it was shown that 3Cpro-induced cell death was efficiently blocked by ferroptosis inhibitors and was accompanied by intense lipid peroxidation. Taken together, these results indicate that 3Cpro induces ferroptosis upon its individual expression in human cells. This is the first demonstration that a proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD.
  • 799
  • 22 Sep 2021
Topic Review
HGPS and Cardiovascular Disease
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease that recapitulates many symptoms of physiological aging and precipitates death. Patients develop severe vascular alterations, mainly massive vascular smooth muscle cell loss, vessel stiffening, calcification, fibrosis, and generalized atherosclerosis, as well as electrical, structural, and functional anomalies in the heart. As a result, most HGPS patients die of myocardial infarction, heart failure, or stroke typically during the first or second decade of life. No cure exists for HGPS, and therefore it is of the utmost importance to define the mechanisms that control disease progression in order to develop new treatments to improve the life quality of patients and extend their lifespan. Since the discovery of the HGPS-causing mutation, several animal models have been generated to study multiple aspects of the syndrome and to analyze the contribution of different cell types to the acquisition of the HGPS-associated cardiovascular phenotype.
  • 868
  • 22 Sep 2021
Topic Review
Let-7e Differentiates Stress-Resilient from Susceptible
Three strains of mice with various susceptibilities to restraint stress (RS), i.e., mice with a knocked out norepinephrine transporter gene (NET-KO), SWR/J and C57BL/6J (WT) mice were shown to serve as a good model to study the molecular mechanisms underlying different stress-coping strategies. We identified 14 miRNAs that were altered by RS in the PFC of these mice in a genotype-dependent manner, where the most interesting was let-7e. Further in silico analysis of its potential targets allowed us to identify five mRNAs (Bcl2l11, Foxo1, Pik3r1, Gab1 and Map2k4), and their level alterations were experimentally confirmed. A next-generation sequencing (NGS) approach, which was employed to find transcripts differentially expressed in the PFC of NET-KO and WT mice, showed that, among others, two additional mRNAs were regulated by mmu-let-7e, i.e., mRNAs that encode Kmt2d and Inf2. Since an increase in Bcl2l11 and Pik3r1 mRNAs upon RS in the PFC of WT mice resulted from the decrease in mmu-let-7e and mmu-miR-484 regulations, we postulated that MAPK, FoxO and PI3K-Akt signaling pathways were associated with stress resilience, although via different, genotype-dependent regulation of various mRNAs by let-7e and miR-484. However, a higher level of Kmt2d mRNA (regulated by let-7e) that was found with NGS analysis in the PFC of NET-KO mice indicated that histone methylation was also important for stress resilience. 
  • 325
  • 22 Sep 2021
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