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Topic Review
Neutral CB1 Receptor Antagonists
Cannabinoid receptor 1 (CB1R) has been one of the major targets in medication development for treating substance use disorders (SUDs). Early studies indicated that rimonabant, a selective CB1R antagonist with an inverse agonist profile, was highly promising as a therapeutic for SUDs.
  • 1.9K
  • 20 Jan 2023
Topic Review
Thymic Epithelial Cells
The thymus is a primary lymphoid organ derived from the endoderm of the 3rd pharyngeal pouch implicated in the maturation of thymocytes and, therefore, key for establishing the immune surveillance. This organ does not contain self-renewing lymphoid precursor cells and therefore, is colonized by lymphoid precursors coming either from the fetal liver through mesenchyme or from the adult bone marrow via the blood vessels [1]. Within the thymus, the developing thymocytes move throughout a 3D thymic epithelial (TE) network, interacting with the thymic epithelial cells (TECs) of two histologically different compartments: the cortex and the medulla [2].
  • 1.9K
  • 26 Oct 2020
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.
  • 1.9K
  • 22 Sep 2021
Topic Review
Entosis and Cell Adhesion
Entosis is a phenomenon, in which one cell enters a second one. New clinico-histopathological studies of entosis prompted us to summarize its significance in cancer. It appears that entosis might be a novel, independent prognostic predictor factor in cancer histopathology. We briefly discuss the biological basis of entosis, followed by a summary of published clinico-histopathological studies on entosis significance in cancer prognosis. The correlation of entosis with cancer prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma and breast ductal carcinoma, is shown. Numerous entotic figures are associated with a more malignant cancer phenotype and poor prognosis in many cancers. We also showed that some anticancer drugs could induce entosis in cell culture, even as an escape mechanism. Thus, entosis is likely beneficial for survival of malignant cells, i.e., an entotic cell can hide from unfavourable factors in another cell and subsequently leave the host cell remaining intact, leading to failure in therapy or cancer recurrence. Finally, we highlight the potential relationship of cell adhesion with entosis in vitro, based on the model of the BxPc3 cells cultured in full adhesive conditions, comparing them to a commonly used MCF7 semiadhesive model of entosis.
  • 1.9K
  • 08 Sep 2020
Topic Review
Neutrophil Extracellular Traps
"Neutrophil extracellular traps" (NETs) are released by neutrophils. Neutrophils act as the first line of defense during infection and inflammation. Once activated, they are able to fulfil numerous tasks to fight inflammatory insults while keeping a balanced immune response. Besides well-known functions, such as phagocytosis and degranulation, neutrophils are also able to release “neutrophil extracellular traps” (NETs).. In response to most stimuli, the neutrophils release decondensed chromatin in a NADPH oxidase-dependent manner decorated with histones and granule proteins, such as neutrophil elastase, myeloperoxidase, and cathelicidins. Although primarily supposed to prevent microbial dissemination and fight infections, there is increasing evidence that an overwhelming NET response correlates with poor outcome in many diseases. Lung-related diseases especially, such as bacterial pneumonia, cystic fibrosis, chronic obstructive pulmonary disease, aspergillosis, influenza, and COVID-19, are often affected by massive NET formation. Highly vascularized areas as in the lung are susceptible to immunothrombotic events promoted by chromatin fibers. Keeping this fragile equilibrium seems to be the key for an appropriate immune response. Therapies targeting dysregulated NET formation might positively influence many disease progressions.
  • 1.9K
  • 13 Aug 2021
Topic Review
Adenosine in inflammation and neoplasia
Adenosine is a purine nucleoside, resulting from the degradation of adenosine triphosphate (ATP). Under adverse conditions, including hypoxia, ischemia, inflammation, or cancer, the extracellular levels of adenosine increase significantly. Once released, adenosine activates cellular signaling pathways through the engagement of the four known G-protein-coupled receptors, adenosine A1 receptor subtype (A1), A2A, A2B, and A3. These receptors, expressed virtually on all immune cells, mitigate all aspects of immune/inflammatory responses. These immunosuppressive effects contribute to blunt the exuberant inflammatory responses, shielding cells, and tissues from an excessive immune response and immune-mediated damage.
  • 1.9K
  • 27 Oct 2020
Topic Review
Regulation of CD36 Expression and Activity in Cancer
Cluster of differentiation 36 (CD36) is a cell surface scavenger receptor that plays critical roles in many different types of cancer, notably breast, brain, and ovarian cancers. While it is arguably most well-known for its fatty acid uptake functions, it is also involved in regulating cellular adhesion, immune response, and apoptosis depending on the cellular and environmental contexts.
  • 1.9K
  • 15 Jun 2023
Topic Review
Brain Microvascular Pericytes in Breast Cancer Brain Metastasis
Brain tissue contains the highest number of perivascular pericytes compared to other organs. Pericytes are known to regulate brain perfusion and to play an important role within the neurovascular unit (NVU). The high phenotypic and functional plasticity of pericytes make this cell type a prime candidate to aid physiological adaptations but also propose pericytes as important modulators in diverse pathologies in the brain. This research highlights known phenotypes of pericytes in the brain, discusses the diverse markers for brain pericytes, and reviews current in-vitro and in-vivo experimental models to study pericyte function.
  • 1.9K
  • 05 May 2022
Topic Review
Cell Transdifferentiation and Reprogramming
Cell transdifferentiation and reprogramming refers to a group of approaches that allow researchers to halt/reverse the development of adult cells, or convert them one from one cell type to another. The manipulation of cell fate can be achieved by enrolling exogenous/artificial controls. The chemical/small molecule and regulatory components of transcription machinery serve as potential tools to execute cell transdifferentiation and have thereby uncovered new avenues for disease modeling and drug discovery. At the advanced stage, one can believe these methods can pave the way to develop efficient and sensitive gene therapy and regenerative medicine approaches.
  • 1.9K
  • 03 Nov 2021
Topic Review
Role of TCA Cycle-Related Enzymes in Human Diseases
The tricarboxylic acid (TCA) cycle, also known as the citrate acid cycle, is a series of chemical reactions to form energy required for cellular function through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. There are eight enzymes in the TCA cycle that oxidize acetyl-coenzyme A (acetyl-CoA), and genetic or non-genetic alterations in these enzymes are closely associated with human diseases, especially cancer and neurodegeneration, but the role of these eight enzymes remains unclear.
  • 1.9K
  • 09 Dec 2021
Topic Review
Photodynamic Therapy: Principles and Reaction Mechanisms
Photodynamic therapy (PDT) is a two-stage treatment that implies the use of light energy, oxygen, and light-activated compounds (photosensitizers) to elicit cancerous and precancerous cell death after light activation (phototoxicity). The biophysical, bioengineering aspects and its combinations with other strategies are highlighted herein, both conceptually and as they are currently applied clinically. Advancements of PDT with the use of nanotechnology are further explored, including quantum dots as innovative photosensitizers or energy donors as well as the combination of PDT with radiotherapy and immunotherapy as future promising cancer treatments. Finally, the potential significance of organoids as physiologically relevant models for PDT has been emphasized.
  • 1.8K
  • 26 Jan 2024
Topic Review
Pharmacological Activation of AMPK
The AMP-activated protein kinase (AMPK) is the central component of a signaling pathway that is conserved in essentially all eukaryotes, the exceptions being a few parasites (e.g., Plasmodium falciparum, the causative agent of malaria) that spend most of their life cycle living inside other eukaryotic cells, in which case the host cell provides AMPK and the parasite may therefore have been able to dispense with it. AMPK is activated by various stresses that act via both classical (canonical) and non-classical (non-canonical) pathways. Pharmacological activation of AMPK can also be achieved via a range of mechanisms. Here, we enumerate the different classes of AMPK activators and describe their mechanisms of action.
  • 1.8K
  • 27 Jan 2021
Topic Review
Sequences Involved in Glycosyltransferase ER-Golgi Trafficking
Glycosyltransferases (GTs) catalyze the glycosylation reaction between activated sugar and acceptor substrate to synthesize a wide variety of glycans. GTs are involved in metabolic processes, signal pathways, cell wall polysaccharide biosynthesis, cell development, and growth. Glycosylation mainly takes place in the endoplasmic reticulum (ER) and Golgi, where GTs and glycosidases involved in this process are distributed to different locations of these compartments and sequentially add or cleave various sugars to synthesize the final products of glycosylation. Therefore, delivery of these enzymes to the proper locations in the cell is essential and involves numerous secretory pathway components.
  • 1.8K
  • 28 Feb 2022
Topic Review
Hallmarks of Senescence
Aging is a complex process characterized by an ongoing decline in physiological functions, leading to degenerative diseases and an increased probability of death. Cellular senescence has been typically considered as an anti-proliferative process; the chronic accumulation of senescent cells contributes to tissue dysfunction and aging. Recognizing the hallmarks of senescence is crucial for the research and development of therapies against aging.
  • 1.8K
  • 20 Feb 2023
Topic Review
C. albicans
Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people.
  • 1.8K
  • 12 Aug 2021
Topic Review
Female Germ Cell Development
In the present era, infertility is one of the major issues which restricts many couples to have their own children. Infertility is the inability to achieve a clinical pregnancy after regular unprotected sexual intercourse for the period of one year or more. Various factors including defective male or female germ cell development, unhealthy and improper lifestyles, diseases like cancer and associated chemo-or-radiation therapies, congenital disorders, etc., may be responsible for infertility. Therefore, it is highly important to understand the basic concepts of germ cell development including primordial germ cell (PGC) formation, specification, migration, entry to genital ridges and their molecular mechanisms, activated pathways, paracrine and autocrine signaling, along with possible alteration which can hamper germ cell development and can cause adversities like cancer progression and infertility. Knowing all these aspects in a proper way can be very much helpful in improving our understanding about gametogenesis and finding possible ways to cure related disorders. 
  • 1.8K
  • 10 Jun 2021
Topic Review
VDAC1
The voltage-dependent anion channel 1 (VDAC1) protein, is an important regulator of mitochondrial function, and serves as a mitochondrial gatekeeper, with responsibility for cellular fate.
  • 1.8K
  • 26 Nov 2020
Topic Review
Minor Intron Splicing
Pre-mRNA splicing is an essential step in gene expression and is catalyzed by two machineries in eukaryotes: the major (U2 type) and minor (U12 type) spliceosomes. While the majority of introns in humans are U2 type, less than 0.4% are U12 type, also known as minor introns (mi-INTs), and require a specialized spliceosome composed of U11, U12, U4atac, U5, and U6atac snRNPs. The high evolutionary conservation and apparent splicing inefficiency of U12 introns have set them apart from their major counterparts and led to speculations on the purpose for their existence.
  • 1.8K
  • 21 Jun 2021
Topic Review
Circular Bacterial Chromosome
A circular bacterial chromosome is a bacterial chromosome in the form of a molecule of circular DNA. Unlike the linear DNA of most eukaryotes, typical bacterial chromosomes are circular. Most bacterial chromosomes contain a circular DNA molecule – there are no free ends to the DNA. Free ends would otherwise create significant challenges to cells with respect to DNA replication and stability. Cells that do contain chromosomes with DNA ends, or telomeres (most eukaryotes), have acquired elaborate mechanisms to overcome these challenges. However, a circular chromosome can provide other challenges for cells. After replication, the two progeny circular chromosomes can sometimes remain interlinked or tangled, and they must be resolved so that each cell inherits one complete copy of the chromosome during cell division.
  • 1.8K
  • 25 Nov 2022
Topic Review
Tumor Necrosis Factor -Related Apoptosis-Inducing Ligand Signaling Pathways
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that undergoes proteolytic cleavage to produce an extracellular ligand. TRAIL can bind to decoy receptor 1 (DcR1) which lacks a death domain (DD) altogether, and DcR2 which has a truncated DD. These decoy receptors are unable to induce DISC (death-inducing signaling complex) formation and act as negative regulators of the apoptotic signaling by competitively binding TRAIL. The canonical TRAIL-induced apoptotic signaling pathway is an example of apoptosis mediated through the extrinsic death pathway, which entails activation of cell-surface receptors by a ligand to induce activation of downstream caspases.
  • 1.8K
  • 30 Nov 2022
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