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Surface Engineered Graphene Oxide and Its Derivatives
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Zaira Zaman Chowdhury, Abu Nasser Faisal, Shahjalal Mohammad Shibly, Devarajan Thangadurai, Saher Islam, Jeyabalan Sangeetha
The application of graphene-based materials (Gr, GO, rGO) has been found to produce dosage-dependent cytotoxicity in living organisms. It can cause kidney and liver damage, granuloma on lungs, reduced cell sustainability, and eventually, apoptosis of the cells (Singh 2016). When administered at lower and intermediate doses (0.1 mg and 0.25 mg), GO did not cause apparent toxicity in mice, but it did cause chronic toxicity when administered at a high dose of 0.4 mg (Wang et al. 2010). As GO concentration was increased, it was accumulated in the lysosomes, mitochondria, endoplasm, and the nucleus of the cells and the body organism failed to flush it out. In several studies, rGO was shown to produce apoptosis-mediated cell death at lower dose within a shorter duration of time, but the necrosis became more frequent when the duration and dose were increased (Wang et al. 2010; Chatterjee et al. 2014).
Free Radicals and Antioxidants
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Manganese (Mn) is an essential micronutrient and a trace metal that intervenes in the activity of superoxide dismutase within the mitochondria (111, 214–215). Superoxide dismutase (SOD) is a metalloenzyme and antioxidant enzyme. SOD contains metal such as manganese, copper, zinc, or iron, used as cofactor for the enzyme’s functioning. SOD protects cells from reactive oxygen species (ROS) by decomposing superoxide radical O2.- into molecular oxygen (O2) and hydrogen peroxide (H2O2) by cyclic oxidation and reduction reactions with the active site metal (214–215). In humans, there are three forms of SODs: SOD-1, SOD-2, and SOD-3. SOD1 and SOD3 contain copper and zinc and are located in the cytoplam and the endoplasm, respectively. As for SOD-2, it contains manganese as cofactor and is located in the mitochondria. SOD-2 or Mn-SOD is of great interest to the medical field because of its protection against the deleterious effects of excessive superoxide in disease states (214). Decreased levels of SOD-2 may contribute to the development of certain diseases such as neurodegenerative diseases (Parkinson’s disease and amyotrophic lateral sclerosis), diabetes, and cancer (214–215). Mn deficiency in the body leads to the inactivation of SOD-2 antioxidant enzyme. However, chronic exposure to Mn causes manganism, a manganese poisoning that is a classic ‘pro-oxidant’ disease.
Fenugreek in Management of Primary Hyperlipidaemic Conditions
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Subhash L. Bodhankar, Amit D. Kandhare, Amol P. Muthal
Plant secretory cells synthesize mucilaginous fibres such as pectin, guar, and psyllium hydrocolloid or psyllium seed gum to prevent dryness of the endoplasm of the seed. Such GAL mucilage, heteropolysaccharide in nature and easily water-soluble, was isolated from fenugreek seeds by researchers. Several studies have well documented the anti-hyperlipidaemic potential of fenugreek GAL in various experimental animal models.
Enhanced anti-proliferative efficacy of epothilone B loaded with Escherichia coli Nissle 1917 bacterial ghosts on the HeLa cells by mitochondrial pathway of apoptosis
Published in Drug Development and Industrial Pharmacy, 2018
Wenxing Zhu, Lujiang Hao, Xinli Liu, Orlando Borrás-Hidalgo, Yuyu Zhang
The ultrastructures of the HeLa cells treated with drugs were detected by TEM (Figure 5). The cells normal or treated with ghosts had rich microvilli on the surface of the cells, many mitochondria of integrated structure and rough endoplasm reticulum in the cytoplasm, euchromatin and clear nucleolus in the nucleus. In the cells treated with free Epo B or Epo B-ghosts, cell shrinkage, profound chromatin condensation, nuclear fragmentation as well as a formation of apoptotic bodies, impairment of mitochondrial and nuclear membranes, microvillus missing, and cell disintegration were observed. However, Epo B-ghosts induced more intensive apoptotic changes compared to free Epo B. In summary, the death type of the HeLa cells treated with Epo B free or associated with ghosts was mainly apoptosis.
The broad-spectrum antiviral recommendations for drug discovery against COVID-19
Published in Drug Metabolism Reviews, 2020
Abu Hazafa, Khalil ur-Rahman, Ikram-ul- Haq, Nazish Jahan, Muhammad Mumtaz, Muhammad Farman, Huma Naeem, Faheem Abbas, Muhammad Naeem, Sania Sadiqa, Saira Bano
The coronavirus replication cycle starts after the entry of virus into the host cell, the replication cycle initiates with the translation of viral genome at 5′-proximal open reading frames (OLFs) including ORF1a and ORF1b, which resultingly syntheses two large replicase polyproteins namely pp1a and pp1ab as illustrated in Figure 3. The formation of polyprotein, pp1ab, at the C-terminal domain involves a –1 ribosomal frameshift (RFS) into ORF1b near the 3′ end of ORF1a. This is the principal regulatory mechanism that is responsible for downregulating the expression level of ORF1b-encoded proteins in contrast to ORF1a-encoded nonstructural proteins. Both polyproteins (pp1a and pp1ab) cleaved with the help of several internal proteases (TMPRSS2) (see Supplementary Material; Abbreviation), and resulted in the assembly of viral nonstructural proteins (nsps) in the form of RTC (de Wilde et al. 2017). The proteolytic cleavage of both polyproteins (pp1a and pp1ab) by internal ORF1a-encoded proteases fallouts in the 15 mature replicases proteins. These replicase proteins comprise several types of enzymes, including helicase (nsp 13), exoribonuclease (nsp 14), RNA-dependent RNA polymerase (nsp 12), and RNA cap-modifying methyltransferases (nsp 14 and 16) which helped in the enzymatic activities and functions, necessary for viral RNA synthesis and capping (Snijder et al. 2016). Finally, after the replication and transcription, the viral genome is packed into nucleocapsids (enveloped from smooth endoplasm reticulum by budding) and ultimately leave the cell through the exocytic pathway (Ulasli et al. 2010; de Wilde et al. 2017).
Optimization and kinetic modeling of interchain disulfide bond reoxidation of monoclonal antibodies in bioprocesses
Published in mAbs, 2020
Peifeng Tang, Zhijun Tan, Vivekh Ehamparanathan, Tingwei Ren, Laurel Hoffman, Cheng Du, Yuanli Song, Li Tao, Angela Lewandowski, Sanchayita Ghose, Zheng Jian Li, Shijie Liu
Glutathione (GSH)/glutathione disulfide (GSSG) is the most important redox pair in the endoplasm reticulum (ER), where antibody is synthesized, folded, and assembled.28 Previous in-vitro experiments demonstrated that a GSH/GSSG ratio similar to that found in the ER could efficiently oxidize active-site cysteine in protein dimerization isomerase, which then could lead to the disulfide formation of substrate proteins.28–30 Since the intracellular disulfide formation is regulated by the redox system, we applied the same principle in an in-vitro environment. Cysteine (Cys) and cystine (Cys-Cys) have been reported as an effective combination to reoxidize reduced mAb fragments to form intact mAb.30–32 In addition, the use of these two redox components is not expected to pose any product safety concerns as both are common upstream media components. Thus, we carried out in-solution studies to evaluate the possibilities of reoxidizing the reduced mAb-1 using a redox system containing varied amounts of cysteine and cystine. GSH was included in the studies due to its wide use in process development. Factors including pH and temperature were also evaluated. The starting material was a partially reduced mAb-1 molecule containing L, HL, HH, HHL, and H2L2 (intact mAb). Figure 2 showed a typical dynamic profile of mAb species overtime in an in-vitro redox system containing cysteine/cystine pair at pH 8. This allowed us to assess the possibility of adapting the principle of intracellular redox system into the in-vitro redox system without further optimizing the redox components and pH condition. The starting material, composed of less than 5% intact mAb-1 (presented as potential worst-case scenario), was recovered to reach the final product purity greater than 95% after 24 hours at room temperature.