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Topic Review
Molecular Mechanism of Ferroptosis in Orthopedic Diseases
Programmed Cell Death (PCD) is an active and orderly process of cell death, which plays an important role in the evolution of living organisms, the stability of the internal environment, and the development of multiple systems. PCD includes cell apoptosis, necrosis, pyroptosis, ferroptosis, and autophagy. Apoptosis is characterized by nuclear fragmentation, the formation of apoptotic bodies, and the activation of proteins such as pro-apoptotic B cell lymphoma-2 (BCL-2). It leads to the increase of mitochondrial outer membrane permeabilization (MOMP) and the production of reactive oxygen species (ROS), thereby releasing apoptotic factors and promoting cysteine cascade activation. During necrosis, the plasma membrane rupture, cytoplasmic organelle swelling, internucleosomal DNA fragmentation deficiency, ATP consumption, and damage-associated molecular patterns (DAMPs) release. When pyroptosis occurs, the plasma membrane ruptures, the inflammation-related active IL-1β and IL-18 are released, and the caspase-1 and gasdermin D (GSDMD) are activated by hydrolysis. Autophagy is characterized by the accumulation of autophagic vacuoles, cytoplasmic vacuolation, non-condensation of chromatin, the transformation of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, and p62-cleaved.
  • 324
  • 19 Oct 2022
Topic Review
Hypoxia-Related Unfolded Protein Response in Tumor Microenvironment
The tumor microenvironment (TME) is a dynamic network that is created by blood vessels, lymphatic vessels, fibroblasts, immune cells as well as components such as the extracellular matrix (ECM) that establishes a “friendly ecosystem” for cancer cells. Hypoxia induces a cellular adaptive response that elevates the expression of the transcription factors called hypoxia-inducible factors (HIFs) that activate the global gene expression changes in both non-malignant and cancer cells. While most of the studies in this area have focused on the canonical responses to hypoxia, a better understanding is needed for the complex molecular changes that are found in the hypoxic TME. These changes include the deregulation of endoplasmic reticulum (ER) homeostasis, and the subsequent perturbations in protein folding and secretion. The potential for erratic protein folding can also lead to another specialized stress response signaling pathway called the unfolded protein response (UPR). The UPR promotes survival during hypoxia by restoring the endoplasmic and mitochondrial homeostasis, but at times, it can also inhibit the cancer cell’s survival. The maturation of transmembrane and secretory proteins that include proangiogenic receptors and ligands as well as ECM remodeling enzymes takes place in the ER. 
  • 238
  • 19 Oct 2022
Topic Review
RNA Vaccine
A ribonucleic acid (RNA) vaccine or messenger RNA (mRNA) vaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine transfects molecules of synthetic RNA into immune cells, where the vaccine functions as mRNA, causing the cells to build foreign protein that would normally be produced by a pathogen (such as a virus) or by a cancer cell. These protein molecules stimulate an adaptive immune response which teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles which protect the RNA strands and help their absorption into the cells. Reactogenicity, the tendency of a vaccine to produce adverse reactions, is similar to that of conventional non-RNA vaccines. People susceptible to an autoimmune response may have an adverse reaction to RNA vaccines. The advantages of RNA vaccines over traditional protein vaccines are ease of design, speed and lower cost of production, and the induction of both cellular and humoral immunity. RNA vaccines, such as the Pfizer–BioNTech COVID-19 vaccine, have the disadvantage of requiring ultracold storage before distribution; other mRNA vaccines, such as the Moderna, CureVac, and Walvax COVID-19 vaccines, do not require such ultracold storage temperatures. In RNA therapeutics, mRNA vaccines have attracted considerable interest as COVID-19 vaccines. In December 2020, Pfizer–BioNTech and Moderna obtained approval for their mRNA-based COVID-19 vaccines. On 2 December, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) became the first medicines regulator to approve an mRNA vaccine, authorizing the Pfizer–BioNTech vaccine for widespread use. On 11 December, the US Food and Drug Administration (FDA) issued an emergency use authorization for the Pfizer–BioNTech vaccine and a week later similarly approved the Moderna vaccine. The use of RNA in vaccines has occasioned substantial misinformation in social media, wrongly claiming that the introduction of RNA alters a person's DNA.
  • 1.2K
  • 18 Oct 2022
Topic Review
Single-Molecule Magnetic Sequencing
Magnetic sequencing is a single-molecule sequencing method in development. A DNA hairpin, containing the sequence of interest, is bound between a magnetic bead and a glass surface. A magnetic field is applied to stretch the hairpin open into single strands, and the hairpin refolds after decreasing of the magnetic field. The hairpin length can be determined by direct imaging of the diffraction rings of the magnetic beads using a simple microscope. The DNA sequences are determined by measuring the changes in the hairpin length following successful hybridization of complementary nucleotides.
  • 435
  • 18 Oct 2022
Topic Review
Molecular Mechanisms of Quercetin in Cancer
The term “ROS (Reactive Oxygen Species)” refers to radicals and ions that contain an unpaired numbered electron in its outmost electron field which are highly reactive metabolic byproducts that can have both harmful and useful effects within the cell. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. Large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells.
  • 883
  • 18 Oct 2022
Topic Review
Mitochondrial Homeostasis
Mitochondria are essential organelles and crucial for cellular survival. Mitochondrial biogenesis and mitophagy are dynamic features that are essential for both maintaining the health of the mitochondrial network and cellular demands. The accumulation of damaged mitochondria has been shown to be related to a wide range of pathologies ranging from neurological to musculoskeletal.
  • 586
  • 18 Oct 2022
Topic Review
Circular Prokaryote Chromosome
A circular prokaryote chromosome is a chromosome in bacteria and archaea, in the form of a molecule of circular DNA. Unlike the linear DNA of most eukaryotes, typical prokaryote chromosomes are circular. Most prokaryote 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.
  • 447
  • 17 Oct 2022
Topic Review
Structure and Function of Peroxiredoxin IV
Peroxiredoxin IV (Prx4) is a 2-Cysteine peroxidase with ubiquitous expression in human tissues. Prx4 scavenges hydrogen peroxide and participates in oxidative protein folding in the endoplasmic reticulum. In addition, Prx4 is secreted outside the cell. Prx4 is upregulated in several cancers and is a potential therapeutic target. Here, the resarchers have summarized the structure and function of Prx4. Oxidative stress is known to activate pro-inflammatory pathways. Chronic inflammation is a risk factor for cancer development. Hence, redox enzymes such as Prx4 are important players in the crosstalk between inflammation and cancer. Understanding molecular mechanisms of regulation of Prx4 expression and associated signaling pathways in normal physiological and disease conditions should reveal new therapeutic strategies. Although Prx4 is a promising therapeutic target for inflammatory diseases and cancer, further research needs to be conducted to bridge the gap to clinical application. 
  • 458
  • 17 Oct 2022
Topic Review
Glioblastoma-Specific Strategies of Vascularization
Angiogenesis has long been implicated as a crucial process in Glioblastoma (GBM) growth and progression. GBM can adopt several strategies to build up its abundant and aberrant vasculature. Targeting GBM angiogenesis has gained more and more attention in anti-cancer therapy, and many strategies have been developed to interfere with this hallmark.
  • 388
  • 17 Oct 2022
Topic Review
Mechanisms of Cathepsins in Hepatocellular Carcinoma
Cathepsins are lysosomal proteases that are essential to maintain cellular physiological homeostasis and are involved in multiple processes, such as immune and energy regulation. Cathepsins are also involved in pathological situations, especially when they are secreted and enter the extracellular space. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and it is the third leading cause of cancer-related deaths worldwide. Cathepsins are involved in the pathology of HCC through acting in proliferation, apoptosis, angiogenesis, invasion and metastasis, metabolism and immunity. 
  • 701
  • 14 Oct 2022
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