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Exploring Alternative Taxol Sources: Biocatalysis of 7-β-Xylosyl-10- Deacetyltaxol and Application for Taxol Production
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Wan-Cang Liu, Bing-Juan Li, Ting Gong, Ping Zhu
Bioactive agents harvested from natural sources often do not provide adequate quantities of an interested product in a sustainable manner. The protection and sustainable utilization of natural resources has been the most important global problem of the 21st century. One of these compounds is Taxol (Taxol®, the generic name: paclitaxel), arguably the most successful anticancer drug of all time, was structurally defined in 1971 and first gained marketing approval from the U.S. Food and Drug Administration (FDA) in 1992 (Liu et al., 2016a). This complex diterpene alkaloid is characterized by the presence of a taxane ring and an N atom in the phenylisoserine lateral chain (Weaver, 2014). It exerts anticancer activity through promoting tubulin assembly into microtubules and preventing their disassembly. Indications include refractory ovarian cancer, breast cancer and squamous cancers (Cusido et al., 2014). Taxol is also used to treat psoriasis, rheumatoid arthritis, and restenosis for which Taxol is used for the coronary stent or balloon catheter coating (Li et al., 2017). Consequently, there is a worldwide market for Taxol and compounds with similar molecular structures.
Carriers for Brain Targeting
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Nanocarriers for Brain Targeting, 2019
Md. Sahab Uddin, Mst. Marium Begum
Neurodegenerative diseases indicate similar pathological features such as abnormal protein aggregation, mitochondrial dysfunction, and disease-specific neuronal degeneration (Maday et al., 2014; Millecamps and Julien, 2013). There are several pathogenic proteins, such as tau, a-synuclein, parkin, leucine-rich repeat kinase 2, and Huntingtin, related to neurodegenerative diseases which have been indicated to directly bind tubulin or modulate microtubule stability. Recently, increase of lines of evidence suggests that MTAs can ameliorate the pathogenic symptoms in animal models of neurodegenerative diseases (Maday et al., 2014; Millecamps and Julien, 2013). Additionally, for the administration of drugs that directly stabilize microtubules, strategies for tackling microtubule-based transport system are also under development, as impairment in the axonal transport has recently come up as an usual factor in several neurodegenerative diseases such as Alzheimer disease and Parkinson disease (Maday et al., 2014; Millecamps and Julien, 2013).
General Introductory Topics
Published in Vadim Backman, Adam Wax, Hao F. Zhang, A Laboratory Manual in Biophotonics, 2018
Vadim Backman, Adam Wax, Hao F. Zhang
Microtubules are formed by the polymers of alpha and beta tubulin. Microtubules originate (“radiate”) from the microtubule originating center (MTOC), which lies near the nucleus in association with centrioles. The role of microtubules as structural elements is to resist compression. One can think of them as support beams. Microtubules are also found in cell flagella (thus enabling cell motility) and cilia. Cilia are structures protruding from the cell surface that are used to move extracellular material, such as mucus. This function, for example, is important in the respiratory epithelium and helps get rid of foreign microorganisms or inorganic microscopic objects that are trapped in the respiratory mucus in a process called mucociliary escalator. Microtubules also assist in mitosis. Their other function is intracellular transport. Associated with motor proteins dynein and kinesin, microtubules help transport organelles like mitochondria or vesicles across a cell. In this process, dynein and kinesin attach and move toward and from, respectively, a cell center. Furthermore, in cell division (mitosis), microtubules are part of the mitotic spindle, the structure that separates the chromosomes into daughter cells.
Motion of a polymer globule with Vicsek-like activity: from super-diffusive to ballistic behavior
Published in Soft Materials, 2021
Subhajit Paul, Suman Majumder, Wolfhard Janke
The first minimal model in this direction to describe such collective behavior was by Vicsek et al.[7] In this model very simple dynamical rules were used to show the clusters formed by point–like particles. In the last few years, another most studied model in the literature is a system consisting of active Brownian particles (ABP).[2,3,10,13–15] In the Vicsek model at every instant, a particle changes its direction of motion by looking at the average direction of its neighbors. On the other hand, a system with ABP shows activity induced clustering for completely repulsive interactions among the particles.[2,3,10,13–15] In recent years interest has grown in modeling active polymers[5,21–24] which can be visualized as a system of constrained motion of micro–swimmers. They are of relevance for various biological objects, e.g., bacterial flagellum, microtubules, actin filaments, etc. These filamentous objects can deform or bend and play major roles in determining the motion and shape of cells to which they belong.[25] As a specific example, the microtubules that are part of the cytoskeletons in eukaryotic cells are like linear polymers made up of tubulin proteins. They help in maintaining the shape of a cell and its membrane and also work as cargo by taking part in cell motility, intracellular transport, etc., supported by some kind of binding or attachment proteins, viz., kinesin, dyenin, etc.[26] Thus, understanding the dynamics as well as conformational properties of active filaments can help us in elucidating some biological mechanisms.
Dual-encapsulated biodegradable 3D scaffold from liposome and waterborne polyurethane for local drug control release in breast cancer therapy
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Hang Yin, Bohong Du, Yue Chen, Nijia Song, Zhen Li, Jiehua Li, Feng Luo, Hong Tan
Up to 2019, breast cancer remains one of the major cancer in women, occupying 30% of female cancers and 15% of cancer death [1]. Effective and precise treatment for breast cancer is urgently needed due to its fast invasion and rapid relapse characteristics [2]. At present, surgical resection combined with chemotherapy is the mainstream treatment strategy [3]. It turns out that surgery cannot completely remove cancerous tissue [4]. Chemotherapy is carried out to further restraint tumor metastasis and recurrence. For example, paclitaxel (PTX) is a natural diterpene alkaloid anti-cancer drug. Paclitaxel can induce tubulin polymerization to make microtubules stable and inhibit mitosis of cancer cells, thus preventing the proliferation of cancer cells [5]. However, for most chemotherapy drugs, the insolubility in water and toxicity to normal tissue growth severely limit their application and bioavailability. Therefore, how to deliver paclitaxel to tumor region more effectively becomes an important problem in chemotherapy. Development of drug carrier systems provides an opportunity to address these issues. Drug carrier system encapsulating poorly soluble drugs is expected to effectively and accurately release drug to the lesion area while reduce the damage to normal organs [6–11]. For the treatment strategy of breast cancer, embedding local drug release materials in the resection area provides a research platform for a lot of exploration.
Learning, memory deficits, and impaired neuronal maturation attributed to acrylamide
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Seulah Lee, Hee Ra Park, Joo Yeon Lee, Jung-Hyun Cho, Hye Min Song, Ah Hyun Kim, Wonjong Lee, Yujeong Lee, Seung-Cheol Chang, Hyung Sik Kim, Jaewon Lee
GAP-43 is localized at presynaptic terminals and expressed in neurons during axonal development and during regeneration of neural connections. Synaptophysin, a synaptic vesicle protein is an integral membrane phosphoprotein that plays a key role during calcium-dependent synaptic transmission (Fernandes et al. 2017). Furthermore, the expression levels of GAP-43 and synaptophysin are critical for establishing neural circuitry and for regulating neurotransmitter release and synaptic plasticity (Chambers et al. 2005; Jahn et al. 1985; Snipes et al. 1987; Webster et al. 2001). β-III-Tubulin is the main structural protein present in microtubules and found in cells of the nervous system (Korzhevskii, Karpenko, and Kirik 2011). Therefore, it is postulated that 500 μM ACR impaired neuronal networking and synaptic plasticity of primary cortical neuron without producing neuronal lethality.