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Topic Review
Viral Purification in Vaccine Processing
Viral vectors and viral vaccines are invaluable tools in prevention and treatment of diseases. About 14% of vaccines approved by the FDA involve enveloped viruses, while out of the 15 gene therapy products approved worldwide in 2019, six of them use enveloped viruses, and 39% of gene therapy clinical trials are using enveloped viruses. Enveloped viruses are encased in a lipid bilayer which, in most cases, fuses with the target host cell membrane to infect cells. These enveloped viruses are produced in various systems, including traditional embryonated chicken eggs or more advanced cell culture technologies such as MRC-5 cells, Vero cells and HEK293-derived cell lines. The manufacturing of viral vector and viral vaccine products has always been paved with challenges related to the downstream processing. Purification process unit operations usually start with harvest and clarification, followed by intermediate purification steps, before polishing and formulation steps. Although techniques have greatly improved over the years to generate purer high-quality products and reproducible processes while maintaining or decreasing the cost of goods, regulatory agencies are increasingly stringent regarding product identity and characterization of the end products and level of acceptable impurities as a way to ensure public safety and maintain public trust in this class of medicine.
  • 1.0K
  • 09 Aug 2021
Topic Review
In Vivo Methods for Measuring the Glycemic Index
The concept of Glycemic Index (GI) was suggested by Jenkins to classify carbohydrate-containing foods. GI is “an expression of the percentage of the area under the blood glucose response curve when taking the same amount of carbohydrate as glucose”. It is a physiological way to explain how dietary carbohydrate impacts blood glucose. The GI value has a range between 1 and 100. Glucose, as the reference material, has a GI value of 100. A food with a lower GI value (≤54) raises blood glucose more slowly.
  • 1.0K
  • 12 May 2022
Topic Review
Osteoclasts
There are sexually dimorphic differences in osteoclast formation and function that may have significant importance for understanding why females are prone to have a lower bone mass than males at any given age and are at increased risk for osteoporosis. Osteoclasts are the principal mediators of bone resorption. They form through the fusion of mononuclear precursor cells under the principal influence of the cytokines macrophage colony stimulating factor (M-CSF, aka CSF-1) and receptor activator of NF-κB ligand (RANKL, aka TNFSF11).
  • 1.0K
  • 04 Nov 2020
Topic Review
PI3K/AKT/mTOR Signaling Pathway
The PI3K/AKT/mTOR complex is a signaling pathway with a major role in essential cellular activities, such as: cell metabolism, cell growth, cell proliferation, apoptosis, and angiogenesis.
  • 1.0K
  • 12 Jan 2021
Topic Review
DNA Methylation and AP-1 Signaling
Epigenetic regulation and modification govern the transcriptional mechanisms that promote disease initiation and progression, but can also control the oncogenic processes, cell signaling networks, immunogenicity, and immune cells involved in anti-inflammatory and anti-tumor responses. 
  • 1.0K
  • 27 Mar 2021
Topic Review
L19-TNF
Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. There is  a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity. 
  • 1.0K
  • 29 Mar 2022
Topic Review
Endothelial Nitric Oxide Synthase
Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupling” of the enzyme by adverse regulation of well-defined “redox switches” in eNOS itself or up-/down-stream signaling molecules. 
  • 1.0K
  • 01 Dec 2021
Topic Review
Generation of Reactive Oxygen Species by Mitochondria
Reactive oxygen species (ROS) are series of chemical products originated from one or several electron reductions of oxygen. ROS are involved in physiology and disease and can also be both cause and consequence of many biological scenarios. Mitochondria are the main source of ROS in the cell and, particularly, the enzymes in the electron transport chain are the major contributors to this phenomenon. 
  • 1.0K
  • 24 May 2022
Topic Review
Zinc Signaling in Prostate Cancer
Prostate cancer (PCa) is one of the most common cancers and the second leading cause of cancer-related death among men worldwide. Despite progresses in early diagnosis and therapeutic strategies, prognosis for patients with advanced PCa remains poor. Therefore, it is necessary to develop novel strategies to prevent, diagnose and effectively treat PCa patients in clinic. Noteworthily, a unique feature of healthy prostate is its highest level of zinc content among all soft tissues in the human body, which dramatically decreases during prostate tumorigenesis. Here, we discuss clinical applications of zinc-containing compounds and proteins involved in PCa signaling pathways. Based on currently available studies, we conclude that zinc can serve as a biomarker in PCa diagnosis and therapies.
  • 1.0K
  • 05 Nov 2021
Topic Review
BDNF expression in GABAergic interneurons
Brain-derived neurotrophic factor (BDNF) is a major neuronal growth factor that is widely expressed in the central nervous system. It is synthesized as a glycosylated precursor protein, (pro)BDNF and post-translationally converted to the mature form, (m)BDNF. BDNF is known to be produced and secreted by cortical glutamatergic principal cells (PCs); however, it remains a question whether it can also be synthesized by other neuron types, in particular, GABAergic interneurons (INs). Therefore, we utilized immunocytochemical labeling and reverse transcription quantitative PCR (RT-qPCR) to investigate the cellular distribution of proBDNF and its RNA in glutamatergic and GABAergic neurons of the mouse cortex. Immunofluorescence labeling revealed that mBDNF, as well as proBDNF, localized to both the neuronal populations in the hippocampus. The precursor proBDNF protein showed a perinuclear distribution pattern, overlapping with the rough endoplasmic reticulum (ER), the site of protein synthesis. RT-qPCR of samples obtained using laser capture microdissection (LCM) or fluorescence-activated cell sorting (FACS) of hippocampal and cortical neurons further demonstrated the abundance of BDNF transcripts in both glutamatergic and GABAergic cells. Thus, our data provide compelling evidence that BDNF can be synthesized by both principal cells and INs of the cortex.
  • 1.0K
  • 26 Oct 2020
Topic Review
Principal Postulates of Centrosomal Biology
The centrosome, which consists of two centrioles surrounded by pericentriolar material, is a unique structure that has retained its main features in organisms of various taxonomic groups from unicellular algae to mammals over one billion years of evolution. In addition to the most noticeable function of organizing the microtubule system in mitosis and interphase, the centrosome performs many other cell functions. In particular, centrioles are the basis for the formation of sensory primary cilia and motile cilia and flagella. Another principal function of centrosomes is the concentration in one place of regulatory proteins responsible for the cell's progression along the cell cycle. Despite the existing exceptions, the functioning of the centrosome is subject to general principles.
  • 1.0K
  • 15 Oct 2020
Topic Review
The Dual Role of Reactive Oxygen Species
The phrase “reactive oxygen species” (ROS) is commonly used to describe the highly reactive free radicals and molecules originating from molecular oxygen. This so-called bi-radical state of oxygen explains its reactivity: one of its electrons can be paired with an external electron with an antiparallel spin, resulting in the production of the highly reactive superoxide radical (O2·−). Since the superoxide radical is weakly basic and highly soluble in water at physiological pH, cellular membranes are relatively impermeable to it. However, O2·− can be converted into membrane-permeable H2O2 by superoxide dismutase (SOD) or protonated to hydroperoxyl radicals (HOO·). Furthermore, O2·− reacts with H2O2 through the Haber–Weiss reaction using iron catalysis, resulting in the formation of highly reactive and cytotoxic hydroxyl radicals (HO·). Furthermore, during the hydroperoxide and polyunsaturated fatty acid metabolism, other types of ROS, namely the peroxyl (ROO·) and alkoxyl (RO·) radicals, are formed as intermediates. On the one hand, high amounts of ROS may damage biomolecules due to their high reactivity. On the other hand—at strictly regulated levels—ROS are essential to maintaining the redox homeostasis of the cells, and they are engaged in many cellular signalling pathways, so their total elimination by the antioxidant system is not expedient.
  • 1.0K
  • 13 May 2022
Topic Review
Toll-Like Receptor 2
TLRs are one of four major families of pattern recognition receptor (PRRs), which include also NOD-like receptors (NLRs), RIG-like receptors (RLRs), C-type lectin receptors (CLRs), and represent the cornerstone of the innate immune response. TLR2, together with TLR1, TLR3, TLR4, and TLR5, was first identified and characterized in 1998. TLR2 is the only TLR that forms functional heterodimers with more than two other types of TLRs, forming dimers with TLR1, TLR6, and in some cases with TLR4. TLR2 recognizes molecules frequently associated with pathogens, the so-called pathogen-associated molecular patterns (PAMPs), leading to activation of downstream signal transduction pathways, which result in the production of inflammatory cytokines, type I interferons (IFNs), and other mediators necessary for the development of effective immune responses. Moreover, TLR2 is involved in the recognition of damage-associated molecular patterns (DAMPs), released by damaged tissues.
  • 1.0K
  • 18 Dec 2020
Topic Review
Platelet
Platelets are small, anucleate blood cells produced by megakaryocytes. The main function of platelets is to participate in the physiological process of haemostasis, allowing bleeding to stop at the site of an injury, while maintaining normal blood flow elsewhere in the circulation. Platelets are also involved in immunity, antimicrobial defense, cancer growth and metastasis, lymphangiogenesis, inflammatory diseases, wound healing, liver regeneration and neurodegeneration. Their life span is 7–10 days in human. They are produced by megakaryocytes (MKs), mostly in the bone marrow.
  • 1.0K
  • 11 Mar 2021
Topic Review
Chemical Chaperones
Chemical chaperones are well known as inhibitors of protein and peptide self-assembly, as well as structural stabilizers of misfolded enzymes. We discovered that chemical chaperones inhibit adenine self-assembly both in a yeast model and in vitro. According to our study, chemical chaperones might have a dual function as enhancers of enzyme stability and as inhibitors of toxic metabolite self-assembly. This novel approach could be implemented for the rational design of inhibitors that target metabolite self-assembly as therapeutics for inborn errors of metabolism.
  • 1.0K
  • 15 Sep 2021
Topic Review
Hypoxia-Inducible Factor
The hypoxia signalling pathway enables adaptation of cells to decreased oxygen availability. When oxygen becomes limiting, the central transcription factors of the pathway, hypoxia-inducible factors (HIFs), are stabilised and activated to induce the expression of hypoxia-regulated genes, thereby maintaining cellular homeostasis.
  • 1.0K
  • 18 Jan 2021
Topic Review
GID/CTLH E3 Ligase Complexes
Multi-subunit E3 ligases facilitate ubiquitin transfer by coordinating various substrate receptor subunits with a single catalytic center. Small molecules inducing targeted protein degradation have exploited such complexes, proving successful as therapeutics against previously undruggable targets. The C-terminal to LisH (CTLH) complex, also called the glucose-induced degradation deficient (GID) complex, is a multi-subunit E3 ligase complex highly conserved from Saccharomyces cerevisiae to humans, with roles in fundamental pathways controlling homeostasis and development in several species.
  • 1.0K
  • 09 Jun 2022
Topic Review
Hydrogen Peroxide Formation and Elimination in Mammalian Cells
Hydrogen peroxide (H2O2) is a compound involved in some mammalian reactions and processes. It modulates and signals the redox metabolism of cells by acting as a messenger together with hydrogen sulfide (H2S) and the nitric oxide radical (•NO), activating specific oxidations that determine the metabolic response. 
  • 1.0K
  • 29 Sep 2022
Topic Review
MSC-EVs against Renal Injury
Mesenchymal stem cells (MSCs) have immunomodulatory and regenerative effects in many organs, including the kidney. Emerging evidence has shown that the trophic effects from MSCs are mainly mediated by the paracrine mechanism rather than the direct differentiation of MSCs into injured tissues. These secretomes from MSCs include cytokines, growth factors, chemokines and extracellular vesicles (EVs) containing microRNAs, mRNAs, and proteins. Many research studies have revealed that secretomes from MSCs have potential to ameliorate renal injury in renal disease models, including acute kidney injury and chronic kidney disease through a variety of mechanisms. These trophic mechanisms include immunomodulatory and regenerative effects. In addition, accumulating evidence has uncovered the specific factors and therapeutic mechanisms in MSC-derived EVs. We summarize the  immunomodulatory and regenerative effects of EVs from MSCs.
  • 1.0K
  • 01 Nov 2020
Topic Review
Seaweeds
Seaweeds have a long history of use as food, as flavouring agents, and also used in traditional folk medicine. Seaweed products range from food, feed, and dietary supplements to pharmaceuticals, and from bioenergy intermediates to materials. At present, 98% of the seaweed required by the seaweed industry is provided by five genera and only ten species. The two brown kelp seaweeds Laminaria digitata, a native Irish species, and Macrocystis pyrifera, a native New Zealand species, are not included in these eleven species, although they have been used as dietary supplements and as animal and fish feed. The properties associated with the polysaccharides and proteins from these two species have resulted in increased interest in them, enabling their use as functional foods. Improvements and optimisations in aquaculture methods and bioproduct extractions are essential to realise the commercial potential of these seaweeds.
  • 1.0K
  • 16 Jan 2022
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