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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.
Mechanisms of Nanotoxicity to Cells, Animals, and Humans
Published in Vineet Kumar, Nandita Dasgupta, Shivendu Ranjan, Nanotoxicology, 2018
Belinda Wong Shu Ee, Puja Khanna, Ng Cheng Teng, Baeg Gyeong Hun
Caspases are synthesized in an inactive form known as procaspases. Procaspases are cleaved at specific aspartate cleavage sites and thus activated. Caspases can be divided into three distinct groups based on their functions—initiators, executioners, and inflammatory caspases. Initiator caspases include caspase-8 and caspase-9, which are involved in the extrinsic and intrinsic pathways, respectively. The main function of initiator caspases is to commit cells to death by apoptosis. Executioner caspases such as caspase-3 are involved in the execution pathway after a cell is committed (Cohen 1997). Upon the activation of the execution pathway, the cell's DNA is fragmented and apoptotic bodies are formed. Apoptosis is completed when these apoptotic bodies are taken up by phagocytes and degraded (Elmore 2007). Nanoparticle entry into cells can lead to the activation of apoptosis through a series of events. Given the complex signaling cascades involved in apoptosis, there are plenty of opportunities to detect and assess the activity of apoptotic proteins. DNA fragmentation can be used as a detection method for apoptosis. Similarly, assays involving the detection of caspases, cytochrome c, pro-apoptotic, and anti-apoptotic proteins can also serve as an indicator of apoptosis activation (Elmore 2007).
In Silico Approach to Cancer Therapy
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
Dysregulation of the apoptotic programmed cell death pathway is another characteristic of cancer. Caspases are crucial for apoptosis activation. Caspase proteins are from the cysteine proteases family, which has essential roles in apoptosis. The inhibitors of apoptosis (IAP) can constrain caspases. Legewie et al. (2006) have developed a model based on the caspase-3 and caspase-9 inhibition by IAPs. This results in the generation of implicit positive feedback leading to bistability and irreversibility in caspase activation.
Characterization of green synthesized flaxseed zinc oxide nanoparticles and their cytotoxic, apoptotic and antimigratory activities on aggressive human cancer cells
Published in Inorganic and Nano-Metal Chemistry, 2021
Suray Pehlivanoglu, Cigdem Aydin Acar, Soner Donmez
The caspase activation of A549, HT29, and MDA-MB-231 cells were evaluated under 10, 25, 50 μg/mL concentrations of the ZnO NPs for 48 h. Colorimetric ELISA assays showed that the caspase-3 and −9 activities significantly increased (p > 0.05) in treated cells compare to control. The NPs induced 2.5–3.1-fold caspase-3 and 3.5–4.15-fold caspase-9 activation. Contrary to this, the treated cells did not show any statistically significant caspase-8 activation (Figure 6). The enhanced caspase-3/9 activations in treated cells inferred intrinsic apoptotic pathway. Caspase-3 is the most important apoptotic executioner caspase because it activates death proteases and catalyzes the autoproteolytic cleavage of cellular structures. Caspase-3 can be directly activated by initiator caspases, such as caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway).[48,49] Consequently, it could be said that the toxicity of the green synthesized ZnO NPs was associated with proapoptotic activity through the induction of caspase-3/9 activation.
In vivo experimental study to investigate cytogenotoxicity of a contaminated estuary from Southeastern Brazilian Coast
Published in Journal of Environmental Science and Health, Part A, 2021
Caroline Margonato Cardoso, Camilo Dias Seabra Pereira, Victor Hugo Pereira da Silva, Hirochi Yamamura, Celina Tizuko Fujiyama Oshima, Daniel Araki Ribeiro
Apoptosis is programmed cell death triggered by extrinsic and intrinsic pathway. This is performed by caspases that can be inactive in the absence of apoptotic stimuli. Following apoptotic stimuli, caspases are activated and initiates the apoptotic process.[46] After finishing the apoptotic process, cellular components are encapsulated into apoptotic bodies which have nuclear fractions, cell organelles, DNA, rRNA and mRNA.[47] Our results showed that SVC increased apoptotic bodies in rat liver, whereas decreasing expression of caspase-3 in PIC and SVC groups was noticed. Such findings are intriguing and difficult to explain, particularly because SVC increased apoptotic bodies and decreased caspase-3 expression. Anyway, it seems that SVC water is able to inhibit apoptosis by downregulation of caspase-3 in liver cells. Since the presence of apoptotic bodies is a morphologic approach for detecting apoptosis process in late stages, further studies are welcomed to elucidate the issue.
Heterologous expression of azurin from Pseudomonas aeruginosa in food-grade Lactococcus lactis
Published in Preparative Biochemistry and Biotechnology, 2019
Despite the important advances in modern technology, microorganisms and their products such as the peptides and proteins continue to make a major contribution to the cancer treatment. Therefore, the studies are focused on the use of peptides and proteins produced by microorganisms in the development of new drugs.[1,2] Azurin protein of Pseudomonas aeruginosa displays in vitro cytotoxicity against various cancer cell lines and induces tumor regression in vivo. It enters preferentially cancer cells and promotes apoptosis by stabilizing p53.[3,4] Azurin increases intracellular levels of p53 and Bax, and triggers the release of cytochrome c from mitochondria to the cytosol. This action activates the caspase cascade that initiates apoptotic processing. The Azurin 50-70 peptide (p28) which is composed of 28 amino acids is probably responsible for this case.[5,6]