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Topic Review
Exosomes in Designing Drug Delivery Systems
Exosomes are a subpopulation of extravascular vesicles with a diameter of 30–150 nm. They are cellular-communication mediators, often reaching very distant organism tissues. Information is transferred by exosomal cargo, composed of a wide variety of macromolecules such as nucleic acids, proteins, and lipids. Exosomes possess natural specific cell targeting properties that are desirable in designing targeted macromolecules (DNA and RNA) and drug delivery systems (doxorubicin, paclitaxel, and taxol). In this context, exosomes can be defined as bio-derived drug transporting and protecting devices for the treatment of bacterial (toxoplasmosis and salmonellosis), viral (AIDS and hepatitis B), and cancer (lung, pancreatic, colon, brain, and breast) diseases. Extensive research proves that exosomes’ natural cargo can double-act, both increasing and decreasing the disease severity. In this case, the exosomes need to be prepared, namely, their origin and their cargo need to be screened and known. Thus, appropriate methods for intact and price-effective exosome isolation are needed with further exosome properties description. Among many utilized isolation methods, the most common are ultracentrifugation, polymer-based precipitation, and affinity precipitation-isolation systems, but novel microfluidic methods compromising high efficacy and purity are being developed. 
  • 1.0K
  • 19 Dec 2022
Topic Review
Autophagy in Cancer Cells
The role of autophagy is to degrade damaged or unnecessary cellular structures. Both in vivo and in vitro studies suggest a dual role of autophagy in cancer—it may promote the development of neoplasms, but it may also play a tumor protective function. The mechanism of autophagy depends on the genetic context, tumor stage and type, tumor microenvironment, or clinical therapy used. Autophagy also plays an important role in cell death as well as in the induction of chemoresistance of cancer cells. The following review describes the extensive autophagic cell death in relation to dietary polyphenols and cancer disease. Polyphenols are organic chemicals that exhibit antioxidant, anti-inflammatory, anti-angiogenic, and immunomodulating properties, and can also initiate the process of apoptosis. In addition, polyphenols reduce oxidative stress and protect against reactive oxygen species. This review presents in vitro and in vivo studies in animal models with the use of polyphenolic compounds such as epigallocatechin-3-gallate (EGCG), oleuropein, punicalgin, apigenin, resveratrol, pterostilbene, or curcumin and their importance in the modulation of autophagy-induced death of cancer cells.
  • 1.0K
  • 22 Jan 2021
Topic Review
Controlling Gene Expression in Hypoxia
Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health. 
  • 1.0K
  • 05 Mar 2021
Topic Review
Acid-Sensing Ion Channels and Mechanosensation
Acid-sensing ion channels (ASICs) are mainly proton-gated cation channels, which can be activated by a drop in extracellular pH below 7.0 and triggered by nonproton ligands during physiological pH levels.
  • 1.0K
  • 12 May 2021
Topic Review
Histone Deacetylases and Their Inhibitors in Ischemic Stroke
Cerebral ischemia is the second leading cause of death in the world and multimodal stroke therapy is needed. The ischemic stroke generally reduces the gene expression due to suppression of acetylation of histones H3 and H4. Histone deacetylases inhibitors have been shown to be effective in protecting the brain from ischemic damage. Histone deacetylases inhibitors induce neurogenesis and angiogenesis in damaged brain areas promoting functional recovery after cerebral ischemia.
  • 1.0K
  • 29 Oct 2021
Topic Review
Mitochondria and Aging
Mitochondria orchestrate the life and death of most eukaryotic cells by virtue of their ability to supply adenosine triphosphate from aerobic respiration for growth, development, and maintenance of the ‘physiologic reserve’. Biological aging is characterized by buildup of intracellular debris (e.g., oxidative damage, protein aggregates, and lipofuscin), which fuels a ‘vicious cycle’ of cell/DNA danger response activation (CDR and DDR, respectively), chronic inflammation (‘inflammaging’), and progressive cell deterioration. Therapeutic options that coordinately mitigate age-related declines in mitochondria and organelles involved in quality control, repair, and recycling are therefore highly desirable.
  • 1.0K
  • 29 Mar 2022
Topic Review
Relationships between N-Glycosylation and Disulfide Bonds
N-Glycosylation (NG) and disulfide bonds (DBs) are two prevalent co/post-translational modifications (PTMs) that are often conserved and coexist in membrane and secreted proteins involved in a large number of diseases. Both in the past and in recent times, the enzymes and chaperones regulating these PTMs have been constantly discovered to directly interact with each other or colocalize in the ER. However, beyond a few model proteins, how such cooperation affects N-glycan modification and disulfide bonding at selective sites in individual proteins is largely unknown. More investigations should be encouraged to unveil the hidden relationships of NG and DBs in the majority of membranes and secreted proteins for pathophysiological understanding and biotherapeutic development. 
  • 1.0K
  • 08 Apr 2022
Topic Review
Thromboembolic complications of SARS-CoV-2
Covid-19 has the potential to cause severe damage to many tissues, including systemic inflammatory response syndrome (SIRS), acute respiratory disease syndrome (ARDS), multiorgan involvement, and shock. One of the most feared complications are thromboembolic events which lead to severe clinical phenotypes: worsening of pulmonary conditions, oxygen desaturation, and acute respiratory distress. Management choices should be considered according to the critical or chronic setting.                             Main pathophysiological mechanisms underlying thrombosis from Covid-19 are discussed, including metabolic derangements and hormonal factors.
  • 1.0K
  • 17 Jun 2021
Topic Review
Telomeres and Their Neighbors
Telomeres are essential structures formed from satellite DNA repeats at the ends of chromosomes in most eukaryotes. Satellite DNA repeat sequences are useful markers for karyotyping, but have a more enigmatic role in the eukaryotic cell. More research is needed until there is a complete picture of the biological function of telomere and other DNA satellite sequences, including chromatin structure, chromosome end-protection and species evolution with a particular focus on non-model organisms. The first problem to solve is the identification of telomere repeats, because telomere repeat identity is the foundation for any hypothesis about telomere maintenance and structure, or binding of specific  proteins. Celebrating Gregor Mendel’s anniversary by going to the principles behind the experiments, a selection of recent developments and underexplored areas of research from the past are illustrated in plants and insects. Indeed, much recent work has expanded beyond the human and yeast models traditional in telomere research. Classic methods from the past, and cutting-edge in silico methods are described. These do not require specialized equipment or expensive materials and can be used, often in combination, to aid research into telomeres and satellites. This can both enrich the general understanding of chromosome maintenance mechanisms and further explore the evolution of telomeres and telomerases.
  • 1.0K
  • 22 Sep 2022
Topic Review
Arbuscular Mycorrhizal Fungi and Strigolactone
Plants, the cornerstone of life on Earth, are constantly struggling with a number of challenges arising from both biotic and abiotic stressors. To overcome these adverse factors, plants have evolved complex defense mechanisms involving both a number of cell signaling pathways and a complex network of interactions with microorganisms. Among these interactions, the relationship between symbiotic arbuscular mycorrhizal fungi (AMF) and strigolactones (SLs) stands as an important interplay that has a significant impact on increased resistance to environmental stresses and improved nutrient uptake and the subsequent enhanced plant growth.
  • 1.0K
  • 06 Dec 2023
Topic Review
HIF Activity
The Hypoxia Inducible Factor (HIF) family of heterodimeric transcription factors that consists of 3 HIFα members (namely HIF-1α, HIF-2α, and HIF-3α) and one HIFβ member (HIF-1β, best known as ARNT) is responsible for the transcriptional response of cells to oxygen deprivation.
  • 1.0K
  • 17 Mar 2021
Topic Review
hIAPP Amyloidosis in Type 2 Diabetes Mellitus
Cases of Type 2 Diabetes Mellitus (T2DM) are increasing at an alarming rate due to the rise in obesity, sedentary lifestyles, glucose-rich diets and other factors. Numerous studies have increasingly illustrated the pivotal role that human islet amyloid polypeptide (hIAPP) plays in the pathology of T2DM through damage and subsequent loss of pancreatic β-cell mass. Here researchers provide an up-to-date summary of recent progress in the field, highlighting factors that contribute to hIAPP misfolding and aggregation which have been linked to β-cell cytotoxicity. Understanding the structure of hIAPP and how these factors affect amyloid formation will help better understand how hIAPP misfolds and aggregates and, importantly, help identify potential therapeutic targets for inhibiting amyloidosis so alternate and more effective treatments for T2DM can be developed.
  • 1.0K
  • 29 Apr 2022
Topic Review
Protein Sorting at the Outer Mitochondrial Membrane
Mitochondria are double membrane-bound organelles consisting of an outer membrane, intermembrane space (IMS), inner membrane, and matrix that play critical functions in cells including metabolism, energy production, regulation of intrinsic apoptosis, and maintenance of calcium homeostasis. Mitochondria are fascinatingly equipped with their own genome and machinery for transcribing and translating 13 essential proteins of the oxidative phosphorylation system (OXPHOS). The rest of the proteins (99%) that function in mitochondria in the various pathways described above are nuclear-transcribed and synthesized as precursors in the cytosol. These proteins are imported into the mitochondria by the unique mitochondrial protein import system that consists of seven machineries. Proper functioning of the mitochondrial protein import system is crucial for optimal mitochondrial deliverables, as well as mitochondrial and cellular homeostasis.
  • 1.0K
  • 17 May 2023
Topic Review
Cytotoxic Alkaloids from Marine Sponges
Marine sponges (porifera) have proved to be a prolific source of unique bioactive secondary metabolites, among which the alkaloids occupy a special place in terms of unprecedented structures and outstanding biological activities. Identification of active cytotoxic alkaloids extracted from marine animals, particularly sponges, is an important strive, due to lack of knowledge on traditional experiential and ethnopharmacology investigations. In this report, a comprehensive survey of demospongian bioactive alkaloids in the range 1987–2020 had been performed with a special emphasis on the potent cytotoxic activity. Different resources and databases had been investigated, including Scifinder (database for the chemical literature) CAS (Chemical Abstract Service) search, web of science, Marin Lit (marine natural products research) database. More than 230 representatives of different classes of alkaloids had been reviewed and classified, different genera belonging to the phylum porifera had been shown to be a prolific source of alkaloidal molecules, including Agelas sp., Suberea sp., Mycale sp., Haliclona sp., Epipolasis sp., Monanchora sp., Crambe sp., Reniera sp., and Xestospongia sp., among others. The sufficient production of alkaloids derived from sponges is a prosperous approach that requires more attention in future studies to consider the constraints regarding the supply of drugs, attained from marine organisms.
  • 1.0K
  • 04 Mar 2021
Topic Review
GSK-3 in Neurodegeneration
Glycogen synthase kinase-3 (GSK-3) is a central player in regulating mood behavior, cognitive functions, and neuron viability. Indeed, many targets controlled by GSK-3 are critically involved in progressing neuron deterioration and disease pathogenesis. 
  • 1.0K
  • 06 Mar 2021
Topic Review
Human Mitochondrial Pyruvate Carrier
Human mitochondrial pyruvate carriers (hMPCs), which are required for the uptake of pyruvate into mitochondria, are associated with several metabolic diseases, including type 2 diabetes and various cancers. Yeast MPC was recently demonstrated to form a functional unit of heterodimers. However, human MPC-1 (hMPC-1) and MPC-2 (hMPC-2) have not yet been individually isolated for their detailed characterization, in particular in terms of their structural and functional properties, namely, whether they exist as homo- or heterodimers. In this study, hMPC-1 and hMPC-2 were successfully isolated in micelles and they formed stable homodimers. However, the heterodimer state was found to be dominant when both hMPC-1 and hMPC-2 were present. In addition, as heterodimers, the molecules exhibited a higher binding capacity to both substrates and inhibitors, together with a larger structural stability than when they existed as homodimers. Taken together, our results demonstrated that the hetero-dimerization of hMPCs is the main functional unit of the pyruvate metabolism, providing a structural insight into the transport mechanisms of hMPCs.
  • 1.0K
  • 24 Mar 2021
Topic Review
Carbonic Anhydrases Inhibitors
Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO3−) balancing is governed by a superfamily of enzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the pivotal physiological reaction, consisting of the reversible hydration of the CO2 to HCO3− and protons.
  • 1.0K
  • 08 May 2021
Topic Review
Cannabinoids
Cannabinoids can be classified as (1) endocannabinoids (AEA, 2-AG), (2) phytocannabinoids (THC, CBD), and (3) synthetic analogs (AJA)—. Phytocannabinoids constitute more than 110 chemical compounds, while synthetic analogs are even more numerous.
  • 1.0K
  • 05 Aug 2021
Topic Review
Entrectinib—An Inhibitor of SARS-CoV-2 Cell Entry
This entry describes entrectinib as an antiviral drug.
  • 1.0K
  • 20 Jan 2022
Topic Review
Circulating Tumor DNA in Precision Oncology
Circulating tumor DNA (ctDNA) is a component of cell-free DNA (cfDNA) that is shed by malignant tumors into the bloodstream and other bodily fluids. ctDNA can comprise up to 10% of a patient’s cfDNA depending on their tumor type and burden.
  • 1.0K
  • 09 May 2022
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