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Muscle and Nerve Histology
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
Each muscle fiber contains either a single nucleus or multiple nuclei and a cytoplasm called sarcoplasm, and it is surrounded by a plasma membrane called sarcolemma. The nuclei are usually peripherally located, heterochromatic, and containing fine nucleoli and stippled nucleoplasm. They stain blue with hematoxylin and red with Gomori trichrome. Centrally positioned nuclei for more than 3% of a whole fascicle is considered abnormal.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
It was postulated that immediate disruption of the nucleolin ribosomal RNA G-quadruplex interaction by quarfloxin led to selective inhibition of Pol I-driven transcription. Also, the re-localization of nucleolin to the nucleoplasm was known to be a common response to cellular stress, resulting in selective apoptosis through various different pathways. Interestingly, it has been shown that nucleolin has significant selectivity for the myc G-quadruplex, where it inhibits myc transcription. In early experiments, although quarfloxin did not inhibit myc gene expression in A549 cells growing in vitro after 2 hours of exposure, in other studies the molecule was shown to inhibit myc mRNA expression by 85% in HCT-116 tumor cells isolated from mice after treatment with quarfloxin.
Nonhistone Nuclear Phosphoproteins
Published in Lubomir S. Hnilica, Chromosomal Nonhistone Proteins, 2018
The oocytes of the frog Xenopus laevis contain a protein which facilitates the assembly of nucleosomes in vitro from purified DNA and histones.187 This protein is localized in the nucleoplasm of Xenopus oocytes, where it is the most abundant protein, accounting for 7.5 to 10% of total protein.188–190 The same protein or a protein with immunologically similar determinants is also found in nuclei of a variety of other vertebrates.189 Because of its abundance and its location in a soluble fraction of the nucleoplasm the protein has been named “nucleoplasmin”.191
Developments in pharmacotherapeutic agents for hepatitis B – how close are we to a functional cure?
Published in Expert Opinion on Pharmacotherapy, 2023
Naoshin Khan, Mohamed Ramzi Almajed, Mary Grace Fitzmaurice, Syed-Mohammed Jafri
Understanding the HBV replication cycle allows the development of agents to target various key steps to prevent and mitigate the infection [Figure 1]. HBV attaches to surface cell-associated heparan sulfate proteoglycans and binds to hepatocyte surface receptors. Endocytosis and fusion of the viral envelope occurs at the cellular surface, releasing the viral nucleocapsid into the cytoplasm; entry inhibitors target this step. The nucleocapsid is transported along cellular microtubules to the nucleus where viral DNA is released into the nucleoplasm. Viral DNA undergoes repair by viral polymerases and cellular enzymes to create covalently closed circular DNA (cccDNA) which acts as a template for transcription within the cell. cccDNA utilizes the host cell’s transcription processes to create the viral RNA needed for viral protein production and replication. Viral RNA is then transported to the cytoplasm where it undergoes translation to produce viral proteins; small interfering RNAs target this step. Viral proteins and nuclear material then forms new HBV RNA-containing nucleocapsids; capsid inhibitors and capsid assembly modulators target this step. Polymerases convert these into DNA-containing nucleocapsids; polymerase inhibitors such as nucleos(t)ide analogs and non-nucleos(t)ide analogs target this step. Novel nucleocapsids are thereafter either imported back into the nucleolus where they replicate further or enveloped and secreted out of the cell; HbsAg inhibitors target this step [9,10].
Mechanism of Elian granules in the treatment of precancerous lesions of gastric cancer in rats through the MAPK signalling pathway based on network pharmacology
Published in Pharmaceutical Biology, 2022
Zhirong Yi, Qingling Jia, Yili Lin, Yujiao Wang, Jun Cong, Zhijian Gu, Jianghong Ling, Gan Cai
To further understand the pharmacological mechanism of Elian granules on PLGC, GO function, and KEGG pathway enrichment analyses of the 190 common targets were carried out using the DAVID database. The threshold was set at P < 0.05. We found the biological process function was mainly related to positive regulation of transcription DNA-templated, and drug response. The cellular component was primarily associated with the cytosol, extracellular space, and nucleoplasm. The molecular function was found mainly related to enzyme binding, identical protein binding, and transcription factor binding (Figure 5). KEGG analysis results showed that the treatment of PLGC with Elian granules was mainly related to autophagy and inflammation. The top 10 pathways were the PI3K-Akt, MAPK, FoxO, Ras, TNF, HIF-1, T cell receptor, Toll-like receptor, p53, and prolactin signalling pathways (Figure 6).
Polystyrene nanoparticles: the mechanism of their genotoxicity in human peripheral blood mononuclear cells
Published in Nanotoxicology, 2022
Kinga Malinowska, Bożena Bukowska, Ireneusz Piwoński, Marek Foksiński, Aneta Kisielewska, Ewelina Zarakowska, Daniel Gackowski, Paulina Sicińska
Similarly, the analysis by Zheng, Yuan, and Chunguang (2019) showed DNA damage in rat liver cells (C57BL6-J) exposed to PS-NPs at 5 and 10 µM. Other researchers detected DNA damage in the Hs27 (human fibroblasts) cell line exposed to PS-NPs at 75 µg/mL using the cytokine block micronucleus (CBMN) assay (Poma et al. 2019). In turn, Vecchiotti et al. (2021) showed the formation of micronuclei in colorectal adenocarcinoma cells (HCT116) exposed to high concentrations (800 and 1200 µg/mL) of PS-NPs (100 nm), which indicated their low genotoxic potential. In addition, they observed formation of nuclear buds and protrusions of nucleoplasm. Other studies used white carp (Ctenopharyngodon idella), which was exposed to PS-NPs at 0.04, 34, and 34 µg/L for 20 days. The results showed DNA damage in red blood cells of studied fish (Guimarães et al. 2021). Subsequent studies conducted by Alaraby et al. (2022) revealed a significant increase in the level of DNA damage in Drosophila larvae exposed to PS particles at doses of 0.4 and 2 mg/g of food. They also showed that the exposure to NPs with a diameter of 50 nm induced a higher level of DNA damage than in the case of particles with a diameter of 200 and 500 nm. The above mentioned results are consistent with other studies by Gopinath et al. (2019), Shah et al. (2020), and Brandts et al. (2018) who showed that damage to the genetic material increased along with increasing doses of PS-NPs given to Allium cepa, Ctenopharyngodon Idella, and Mytilus galloprovincialis.