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Topic Review
Muse Cells
Muse cells, identified as pluripotent surface marker, stage-specific embryonic antigen (SSEA)-3(+), are endogenous reparative pluripotent stem cells distributed in the bone marrow, peripheral blood and connective tissue of every organ. Since they are non-tumorigenic and do not require gene introduction or cytokine treatment to be rendered pluripotent and induce differentiation, they elicit few safety concerns. They can be delivered intravenously and do not require surgery for their administration since they selectively home to damaged site by sphingosine-1-phosphate (S1P)-S1PR2 axis after intravenous injection. Donor-Muse cells can be used without HLA-matching test or immunosuppressant treatment since they have a specific immunomodulatory system represented by HLA-G expression.
  • 749
  • 12 Oct 2021
Topic Review
Aberrant Stress Granule Dynamics
Stress granules are membrane-less organelles formed through the process of liquid–liquid phase separation (LLPS) under certain stress conditions, such as oxidative stress and heat shock, among others.
  • 541
  • 12 Oct 2021
Topic Review
GRP94 in Cancer
Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER)-resident member of the heat shock protein 90 (HSP90) family. In physiological conditions, it plays a vital role in regulating biological functions, including chaperoning cellular proteins in the ER lumen, maintaining calcium homeostasis, and modulating immune system function. Recently, several reports have shown the functional role and clinical relevance of GRP94 overexpression in the progression and metastasis of several cancers. Therefore, the current review highlights GRP94’s physiological and pathophysiological roles in normal and cancer cells. Additionally, the unmet medical needs of small chemical inhibitors and the current development status of monoclonal antibodies specifically targeting GRP94 will be discussed to emphasize the importance of cell surface GRP94 as an emerging therapeutic target in monoclonal antibody therapy for cancer.
  • 659
  • 11 Oct 2021
Topic Review
Autoimmune Diseases in Epidermolysis Bullosa
Gene therapy serves as a promising therapy in the pipeline for treatment of epidermolysis bullosa (EB). However, with great promise, the risk of autoimmunity must be considered. While EB is a group of inherited blistering disorders caused by mutations in various skin proteins, autoimmune blistering diseases (AIBD) have a similar clinical phenotype and are caused by autoantibodies targeting skin antigens. Often, AIBD and EB have the same protein targeted through antibody or mutation, respectively. Moreover, EB patients are also reported to carry anti-skin antibodies of questionable pathogenicity. It has been speculated that activation of autoimmunity is both a consequence and cause of further skin deterioration in EB due to a state of chronic inflammation.
  • 772
  • 11 Oct 2021
Topic Review
Antigen Presentation of SARS-CoV-2 mRNA Vaccines
Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of viral Spike S1 protein encoding mRNA incorporated in a lipid nanoparticle and stabilized by polyethylene glycol (PEG). The mRNA vaccines are novel in many respects, including cellular uptake and the intracellular routing, processing, and secretion of the viral protein. Because of space restrictions, viral vector vaccines not discussed in detail. The antigen presentation routes in MHC class I and class II, in relation to the induction of virus-neutralizing antibodies and cytotoxic T-lymphocytes, will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. In rare cases, the mRNA-based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG and potential presentation in the context of CD1 will be discussed. 
  • 1.2K
  • 11 Oct 2021
Topic Review
Skeletal Muscle
Skeletal muscle is composed of multinucleated, mature muscle cells (myofibers) responsible for contraction, and a resident pool of mononucleated muscle cell precursors (MCPs), that are maintained in a quiescent state in homeostatic conditions. Skeletal muscle is remarkable in its ability to adapt to mechanical constraints, a property referred as muscle plasticity and mediated by both MCPs and myofibers. This review summarizes recent insights into the mechanisms underlying nuclear force transmission in MCPs and myofibers. 
  • 1.0K
  • 11 Oct 2021
Topic Review
STAT Proteins in Advanced and Metastasized Prostate Cancer
The STAT proteins bind to specific response elements on the DNA in the nucleus, thereby inducing gene transcription. Based on their various functions, STAT proteins are essential in several health conditions such as autoimmune diseases and cancer. Despite their broad spectrum of activity, only STAT3 affects embryonic development, as shown in STAT3 knock-out mouse experiments.
  • 560
  • 11 Oct 2021
Topic Review
Muscle Regeneration and RNA
In skeletal muscle, regeneration is driven by a reservoir of resident progenitors, called satellite cells, able to efficiently replenish damaged muscle [44]. These cells are not present in the adult cardiac muscle, although a regenerative response, mediated by the proliferation of pre-existing cardiomyocytes, occurs in mice during the first week of life [45,46,47]. Temporal and tissue-specific nuances in the process of regeneration may underlie the participation of still unknown protagonists, whose ability to fine-tune myogenic expression becomes critical in both physiological and pathological conditions. The peculiar properties of RNA, along with its tissue specificity, satisfy the requirements for its integration in regenerative networks and will surely pave the way for future applications in medicine.
  • 446
  • 09 Oct 2021
Topic Review
Hyperinsulinaemia-Osteofragilitas
Bone fragility leading to increased risk of low energy (fragility) fractures that is independent of bone mineral density, occurring in individuals with detected and undetected hyperinsulinaemia. Patients with type 2 diabetes mellitus (T2DM) and/or cardiovascular disease (CVD), conditions of hyperinsulinaemia, have lower levels of osteocalcin and bone remodelling, and increased rates of fragility fractures. Unlike osteoporosis with lower bone mineral density (BMD), T2DM bone fragility “hyperinsulinaemia-osteofragilitas” phenotype presents with normal to increased BMD. Hyperinsulinaemia and insulin resistance positively associate with increased BMD and fragility fractures.  Hyperinsulinaemia enforces glucose fuelling, which decreases NAD+-dependent antioxidant activity. This increases reactive oxygen species and mitochondrial fission, and decreases oxidative phosphorylation high-energy production capacity, required for osteoblasto/cytogenesis. Osteocytes directly mineralise and resorb bone, and inhibit mineralisation of their lacunocanalicular space via pyrophosphate. Hyperinsulinaemia decreases vitamin D availability via adipocyte sequestration, reducing dendrite connectivity, and compromising osteocyte viability. Decreased bone remodelling and micropetrosis ensues. Trapped/entombed magnesium within micropetrosis fossilisation spaces propagates magnesium deficiency (MgD), potentiating hyperinsulinaemia and decreases vitamin D transport. Vitamin D deficiency reduces osteocalcin synthesis and favours osteocyte apoptosis.  Carbohydrate restriction/fasting/ketosis increases beta-oxidation, ketolysis, NAD+-dependent antioxidant activity, osteocyte viability and osteocalcin, and decreases excess insulin exposure. Osteocalcin is required for hydroxyapatite alignment, conferring bone structural integrity, decreasing fracture risk and improving metabolic/endocrine homeodynamics. Patients presenting with fracture and normal BMD should be investigated for T2DM and hyperinsulinaemia.
  • 1.2K
  • 09 Oct 2021
Topic Review
Epitranscriptomics to Improve ICB-Efficacy by Targeting CISH
Epitranscriptomics has contributed greatly to the clinico-biological practices due to its diverse role in regulating at the post-transcriptional and translational levels. Epitranscriptomics is generally referred to chemical modifications in the RNA molecule without changing the nucleotide sequence. So far, more than 160 chemical modifications have been identified; playing a crucial role in regulating various biological processes, for example, in acute myeloid leukemia treatment, lung adenocarcinoma, gastric cancer and broad range tumor types.
  • 521
  • 08 Oct 2021
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