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Bioengineering of Pharmacologically-Active Metabolites for Effective Drug Nano-Formulations from the Callus and Metabolites of Medicinal Plants and Their Significant Application in Nanomedicine
Published in Hajiya Mairo Inuwa, Ifeoma Maureen Ezeonu, Charles Oluwaseun Adetunji, Emmanuel Olufemi Ekundayo, Abubakar Gidado, Abdulrazak B. Ibrahim, Benjamin Ewa Ubi, Medical Biotechnology, Biopharmaceutics, Forensic Science and Bioinformatics, 2022
Charles Oluwaseun Adetunji, Akinola Samson Olayinka, Denisa Ficai, Anton Ficai, Michael Olugbenga Samuel, Wilson Nwankwo, Muhammad Akram, Rumaisa Ansari, Tehreen Riaz, Rida Zainab, Chukwuebuka Egbuna, Oluwaseyi Paul Olaniyan, Hameed Shah, Ruth Ebunoluwa Bodunrinde, Juliana Bunmi Adetunji, Jonathan C. Ifemeje, Michael Chinedu Olisah, Mohammad Ali Shariati, Kingsley Eghonghon Ukhurebor, Daniel Ingo Hefft, Wadzani Dauda Palnam
Also, Recordati et al. (2016) reported that intravenously vaccinated CT- and PVP-coated AgNPs together with Ag acetate into CD-1 mice while Yang et al. (2017) utilized commercially available “CT-AgNPs and PVP-AgNPs” with sizes of 10, 40 and 100 nm. The cytotoxic effect of coated AgNPs has been established to be size-dependent, whereas the kind of coating (which could either be CT or PVP) could hardly have any impact on the bio-distribution of the AgNP present in the organ tissues (Yang et al. 2017). Ma et al. (2015) stated that the RT-qPCR study of the hepatocyte discovered considerable variations in the expression of gene outlines, for example up-regulation of some genes like p53, caspase-3, caspase-8, transferrin (Trf) and Bcl-2. It has been known that caspases are enzymes which could result in apoptosis by slicing the cellular proteins. Caspase 2, 8, 9 and 10, which are initiator caspases, recruit the apoptotic procedure, resulting in the instigation of the effector caspases such as caspase 3, 6 and 7.
Gene Therapy for Retina and Eye Diseases
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Clinical trials are underway for QR-110 (Sepofarsen), an AON for the treatment of patients with LCA10 with ciliopathy gene encoding centrosomal protein 290 (CEP290) point mutation and siRNAs for AMD, nonarteritic anterior ischemic optic neuropathy (NAION), and glaucoma treatment through targeting of the RT801 gene or caspase-2 (QPI-1007) (38).
Graphene Applications in Biology and Medicine
Published in Klaus D. Sattler, st Century Nanoscience – A Handbook, 2020
A comparative study measuring mitochondrial toxicity and cell membrane integrity in neuronal cells has suggested that the biological activity of graphene and single-walled carbon nanotubes (SWCNTs) strongly depends on their shape. Following a 24 h exposure, the metabolic activity of PC12 cells decreases in a variable manner: graphene leads to high toxicity at low concentrations and low toxi-city at high concentrations, even more than compared to SWCNTs. The highest concentration of graphene used in these studies (100 µg/mL) significantly increases the release of LDH (a total LDH level higher than normal is found in diseases such as myocardial infarction, pulmonary infarction, acute viral hepatitis, toxic hepatitis, shock condition, severe anemia, muscular dystrophy, diabetes, renal failure, cirrhosis hepatic, leukemia, and neoplasms; decreased values are found in subjects exposed to ionizing radiation) and the generation of reactive oxygen species (ROS). In addition, caspase-3 activation (there are two types of caspases: initiator caspases (caspase-2, caspase-8, caspase-9, caspase-10) that cut off inactive forms of other caspases called effector (caspase-3), caspase-6, caspase-7) activating them, the effector caspases in turn will cut precise protein substrates, giving rise to the apoptotic process) suggests a time-dependent increase in the apoptotic process at a concentration equal to or greater than 10 µg/mL. Yuan et al. have compared the potential cytotoxicity of graphene and SWCNTs on the HepG2 cell line: overall, a concentration of 1 µg/mL of both nanomaterials led to the different expression of 37 proteins involved in cell metabolism, redox regulation, cytoskeletal formation, and cell growth. An interesting discovery has been that graphene and SWCNTs produce different pathways of expression of calcium-binding proteins, thus indicating a different mode of action. Finally, pristine graphene has been identified as responsible for increased ROS concentration and apoptotic processes of macrophages of RAW 264.7 cell line, important for the innate immunity system.
Nanofabrication of PLGA-PEG-chitosan-folic acid systems for delivery of colchicine to HT-29 cancer cells
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Farzaneh Sadeghzadeh, Atefeh Sadat Ziaratnia, Masoud Homayouni Tabrizi, Ghazal Hosseini Torshizi, Maitham Alhajamee, Davoud Khademi
Castedo et al. were reported that mitotic cell death could be due to defects in cell cycle checkpoints or cell damage. According to the report, activation of caspase-2 in response to DNA damage or activation of caspase-9, caspase-3 and cytochrome c following mitochondrial membrane permeability can lead to mitotic catastrophe [50]. Evidence suggests that treatment with anti-mitotic drugs such as colchicine can disrupt mitotic spindles by stopping the cell cycle, leading to induction of apoptosis in cancer cells through mitotic catastrophe [51]. In this study, the cell cycle and expression of some genes involved in mitotic catastrophe, including caspases, and some proteins of the Bcl-2 family [1] were evaluated. The results of this study showed a change in the expression of genes involved in mitotic catastrophe and the initiation of the intrinsic pathway of apoptosis. According to the results, the increased expression of Bax, caspase 3,9, P53 and P21 genes was confirmed in the treatment with COL-PPCF-NPs. The results of this study generally showed the mechanism of action of colchicine as an anti-mitotic drug similar to previous studies [1, 49, 51]. However, in this study, it was shown that colchicine transfer with nanocarriers can play an effective role in reducing its inhibitory effect on normal cells.
Increase in cysteine-mediated multimerization under attractive protein–protein interactions
Published in Preparative Biochemistry & Biotechnology, 2022
Leo A. Jakob, Tomás Mesurado, Alois Jungbauer, Nico Lingg
Circularly permuted caspase-2, in particular CASPON enzyme, became a potentially interesting industrial enzyme for fusion protein processing.[1–3] This cysteine-dependent protease is the essential element of a platform process for the production of recombinant proteins.[3] The CASPON enzyme is a mutant of human caspase-2 (wtCasp2)[1,4] and exhibits increased enzymatic activity as well as manufacturability compared to wtCasp2.[1,2,5] The high manufacturability of the CASPON enzyme is partially due to the use of a solubility tag.[2]Figure 1 shows the wtCasp2 crystal structure (Figure 1(A), PDB accession number: 1PYO)[4] and an AlphaFold prediction of the CASPON enzyme structure (Figure 1(B & C)).[6–8] The most notable difference is the large, relatively unstructured solubility tag of the CASPON enzyme (Figure 1(C)). The core is structurally similar to wtCasp2, differing in only four amino acids.[1]