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Topic Review
Fluorescent Protein-Based Autophagy Biosensors
Autophagy is an important cellular process of self-degradation for dysfunctional or unnecessary molecules and organelles, thus dysregulation of autophagy can be involved in various diseases such as neurodegenerative diseases. To understand complex process of autophagy and the related diseases, various methods have been developed, for example biochemical, chemical, and imaging assays. In particular, fluorescent protein (FP)-based autophagy biosensors allow sensitive and selective monitoring of autophagy progression in live cells. After the discovery of green fluorescent protein (GFP), a variety of FPs has been discovered and engineered which have different physicochemical properties, such as excitation/emission spectra, Stokes shift, maturation rate, stability, photo-reactivity and pH-sensitivity. Advances in fluorescent protein technology and FP-based biosensors enabled the real-time monitoring of cellular and molecular events in live cells with high spatiotemporal resolutions.
  • 2.2K
  • 22 Jun 2021
Topic Review
Nanoparticles in Lung Cancer Treatment
Lung cancer is managed using conventional therapies, including chemotherapy, radiation therapy, or a combination of both. Each of these therapies has its own limitations, such as the indiscriminate killing of normal as well as cancer cells, the solubility of the chemotherapeutic drugs, rapid clearance of the drugs from circulation before reaching the tumor site, the resistance of cancer cells to radiation, and over-sensitization of normal cells to radiation. Other treatment modalities include gene therapy, immunological checkpoint inhibitors, drug repurposing, and in situ cryo-immune engineering (ICIE) strategy. Nanotechnology has come to the rescue to overcome many shortfalls of conventional therapies.
  • 2.2K
  • 06 Jul 2023
Topic Review
Thymoquinone and COVID-19
Thymoquinone (TQ) is the most pharmacologically active ingredient in Nigella sativa seeds (black seeds); it is reported to have anticancer, anti-inflammatory and antioxidant effects in various settings.
  • 2.2K
  • 02 Jun 2021
Topic Review
Glial Cells in Physiological and Pathological States
Glial cells are the most abundant and widely distributed cells that maintain cerebral homeostasis in the central nervous system. They mainly include microglia, astrocytes, and the oligodendrocyte lineage cells. Moreover, glial cells may induce pathological changes, such as inflammatory responses, demyelination, and disruption of the blood–brain barrier, to regulate the occurrence and development of neurological diseases through various molecular mechanisms.
  • 2.2K
  • 29 Aug 2022
Topic Review
Growth Hormone-Releasing Hormone
Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 (IGF-1). Pituitary-type GHRH-receptors (GHRH-R) are expressed in human lungs, indicating that GHRH or GH could participate in lung development, growth, and repair. The goal of thisentry is to present and critically evaluate new findings regarding growth hormone-releasing hormone (GHRH) and its actions in the settings of lung inflammation, fibrosis, and cancer. The essential, unanswered question we address is whether GHRH, as revealed by synthetic peptide probes that activate or inhibit its receptor, plays key roles in lung pathophysiology that are distinct from its effects on growth and metabolism. It provides background on the physiology of GHRH in the lung, which was elucidated using recently developed GHRH receptor peptide agonists and antagonists as mechanistic probes.
  • 2.2K
  • 09 Nov 2020
Topic Review
Beta-3 Adrenergic Receptor
The beta-3 adrenergic receptor (β3-AR) is by far the least studied isotype of the beta-adrenergic sub-family. Despite its study being long hampered by the lack of suitable animal and cellular models and inter-species differences, a substantial body of literature on the subject has built up in the last three decades and the physiology of β3-AR is unraveling quickly. As will become evident in this work, β3-AR is emerging as an appealing target for novel pharmacological approaches in several clinical areas involving metabolic, cardiovascular, urinary, and ocular disease.
  • 2.2K
  • 05 May 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.
  • 2.2K
  • 18 Oct 2022
Topic Review
Heme Metabolism
Mitochondria are essential organelles of mammalian cells, often emphasized for their function in energy production, iron metabolism and apoptosis as well as heme synthesis. The heme is an iron-loaded porphyrin behaving as a prosthetic group by its interactions with a wide variety of proteins. These complexes are termed hemoproteins and are usually vital to the whole cell comportment, such as the proteins hemoglobin, myoglobin or cytochromes, but also enzymes such as catalase and peroxidases. The building block of porphyrins is the 5-aminolevulinic acid, whose exogenous administration is able to stimulate the entire heme biosynthesis route. In neoplastic cells, this methodology repeatedly demonstrated an accumulation of the ultimate heme precursor, the fluorescent protoporphyrin IX photosensitizer, rather than in healthy tissues.
  • 2.2K
  • 27 Jul 2022
Topic Review
The Microglia in Brain Ischemia-Reperfusion Injury
Microglia represent 10–15% of the total cells in the brain. These cells are considered as the resident macrophages and the first defense line in the central nervous system (CNS) against pathogens. Microglial activation is one of the earliest events after brain ischemia. 
  • 2.2K
  • 20 Jun 2022
Topic Review
Mitochondrial Disease
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions. Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. A subclass of these diseases that have neuromuscular symptoms are known as mitochondrial myopathies.
  • 2.2K
  • 25 Oct 2022
Topic Review
The NLRP3 Inflammasome
As a critical component of the innate immune system, the nucleotide-binding and oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome can be activated by various endogenous and exogenous danger signals. Activation of this cytosolic multiprotein complex triggers the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and initiates pyroptosis, an inflammatory form of programmed cell death. The NLRP3 inflammasome fuels both chronic and acute inflammatory conditions and is critical in the emergence of inflammaging. Recent advances have highlighted that various metabolic pathways converge as potent regulators of the NLRP3 inflammasome. This review focuses on our current understanding of the metabolic regulation of the NLRP3 inflammasome activation, and the contribution of the NLRP3 inflammasome to inflammaging.
  • 2.2K
  • 24 Aug 2020
Topic Review
Mechanisms of Synaptic Vesicle Exo- and Endocytosis
Within 1 millisecond of action potential arrival at presynaptic terminals voltage–gated Ca2+ channels open. The Ca2+ channels are linked to synaptic vesicles which are tethered by active zone proteins. Ca2+ entrance into the active zone triggers: (1) the fusion of the vesicle and exocytosis, (2) the replenishment of the active zone with vesicles for incoming exocytosis, and (3) various types of endocytosis for vesicle reuse, dependent on the pattern of firing. These time-dependent vesicle dynamics are controlled by presynaptic Ca2+ sensor proteins, regulating active zone scaffold proteins, fusion machinery proteins, motor proteins, endocytic proteins, several enzymes, and even Ca2+ channels, following the decay of Ca2+ concentration after the action potential. 
  • 2.2K
  • 13 Jul 2022
Topic Review
Melanin Transfer Models
Skin pigmentation ensures efficient photoprotection and relies on the pigment melanin, which is produced by epidermal melanocytes and transferred to surrounding keratinocytes. While the molecular mechanisms of melanin synthesis and transport in melanocytes are now well characterized, much less is known about melanin transfer and processing within keratinocytes.
  • 2.1K
  • 02 Aug 2023
Topic Review
Peroxisomal Stress Response and Inter-Organelle Communication
Peroxisomes are single membrane-bound organelles found in all eukaryotic cells and organisms, from yeast to plants and mammals. They are key regulators of cellular and metabolic homeostasis. These organelles play important roles in redox metabolism, the oxidation of very-long-chain fatty acids (VLCFAs), and the biosynthesis of ether phospholipids. Given the essential role of peroxisomes in cellular homeostasis, peroxisomal dysfunction has been linked to various pathological conditions, tissue functional decline, and aging. In the past few decades, a variety of cellular signaling and metabolic changes have been reported to be associated with defective peroxisomes, suggesting that many cellular processes and functions depend on peroxisomes. Peroxisomes communicate with other subcellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum (ER), and lysosomes. These inter-organelle communications are highly linked to the key mechanisms by which cells surveil defective peroxisomes and mount adaptive responses to protect them from damages. 
  • 2.1K
  • 15 Feb 2022
Topic Review
Retinoic Acid
The retinoids are a group of compounds including vitamin A and its active metabolite all-trans-retinoic acid (ATRA). Retinoids regulate a variety of physiological functions in multiple organ systems, are essential for normal immune competence, and are involved in the regulation of cell growth and differentiation. Vitamin A derivatives have held promise in cancer treatment and ATRA is used in differentiation therapy of acute promyelocytic leukemia (APL). ATRA and other retinoids have also been successfully applied in a variety of dermatological conditions such as skin cancer, psoriasis, acne, and ichthyosis. Moreover, modulation of retinoic acid receptors and retinoid X (or rexinoid) receptors function may affect dermal cells. The studies using complex genetic models with various combinations of retinoic acid receptors (RARs) and retinoid X (or rexinoid) receptors (RXRs) indicate that retinoic acid and its derivatives have therapeutic potential for a variety of serious dermatological disorders including some malignant conditions.
  • 2.1K
  • 28 Dec 2020
Topic Review
Mitochondrial VDAC1 as Therapeutic Target of Inflammation-Related Diseases
The multifunctional protein, voltage-dependent anion channel 1 (VDAC1), is located on the mitochondrial outer membrane. It is a pivotal protein that maintains mitochondrial function to power cellular bioactivities via energy generation. VDAC1 is involved in regulating energy production, mitochondrial oxidase stress, Ca2+ transportation, substance metabolism, apoptosis, mitochondrial autophagy (mitophagy), and many other functions. VDAC1 malfunction is associated with mitochondrial disorders that affect inflammatory responses, resulting in an up-regulation of the body’s defensive response to stress stimulation. Overresponses to inflammation may cause chronic diseases. Mitochondrial DNA (mtDNA) acts as a danger signal that can further trigger native immune system activities after its secretion. VDAC1 mediates the release of mtDNA into the cytoplasm to enhance cytokine levels by activating immune responses. VDAC1 regulates mitochondrial Ca2+ transportation, lipid metabolism and mitophagy, which are involved in inflammation-related disease pathogenesis. 
  • 2.1K
  • 26 Oct 2022
Topic Review
Targeting CDK4/6 for Anticancer Therapy
Cyclin-dependent kinase 4/6 (CDK4/6) are key regulators of the cell cycle and are deemed as critical therapeutic targets of multiple cancers. Various approaches have been applied to silence CDK4/6 at different levels, i.e., CRISPR to knock out at the DNA level, siRNA to inhibit translation, and drugs that target the protein of interest. Here we summarize the current status in this field, highlighting the mechanisms of small molecular inhibitors treatment and drug resistance.
  • 2.1K
  • 12 Apr 2022
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. 
  • 2.1K
  • 11 Oct 2021
Topic Review
Cyclins and Cyclin-Dependent Kinases in Gastric Cancer
Gastric cancer predominantly occurs in adenocarcinoma form and is characterized by uncontrolled growth and metastases of gastric epithelial cells. The growth of gastric cells is regulated by the action of several major cell cycle regulators including Cyclins and Cyclin-dependent kinases (CDKs), which act sequentially to modulate the life cycle of a living cell. It has been reported that inadequate or over-activity of these molecules leads to disturbances in cell cycle dynamics, which consequently results in gastric cancer development.
  • 2.1K
  • 08 Feb 2023
Topic Review
Limb Development
The function of retinoic acid (RA) during limb development is still debated, as loss and gain of function studies led to opposite conclusions. With regard to limb initiation, genetic studies demonstrated that activation of FGF10 signaling is required for the emergence of limb buds from the trunk, with Tbx5 and RA signaling acting upstream in the forelimb field, whereas Tbx4 and Pitx1 act upstream in the hindlimb field. Early studies in chick embryos suggested that RA as well as Meis1 and Meis2 (Meis1/2) are required for subsequent proximodistal patterning of both forelimbs and hindlimbs, with RA diffusing from the trunk, functioning to activate Meis1/2 specifically in the proximal limb bud mesoderm. However, genetic loss of RA signaling does not result in loss of limb Meis1/2 expression and limb patterning is normal, although Meis1/2 expression is reduced in trunk somitic mesoderm. More recent studies demonstrated that global genetic loss of Meis1/2 results in a somite defect and failure of limb bud initiation. Other new studies reported that conditional genetic loss of Meis1/2 in the limb results in proximodistal patterning defects, and distal FGF8 signaling represses Meis1/2 to constrain its expression to the proximal limb.
  • 2.1K
  • 19 Jan 2021
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