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Immunology of Scleroderma
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
The centromere comprised of the kinetochore, which is a trilaminar disc-shaped structure, serves as the attachment site for the spindle microtubules. The microtubules facilitate the alignment and separation of the chromosome during mitosis.184,185 The prevalence of ACA in SSc varies but has been found to be strongly associated with the lcSSc.134 ACA has also been identified in normal individuals186 and patients with Raynaud’s,166,186 SLE,186 primary biliary cirrhosis,187 and morphea.187 ACA comprises at least 6 centromere polypeptides (CENP): CENP-A to CENP-F More than 90% of ACA-positive sera from SSc patients reacts with CENP-A, -B, and -C188 and studies have demonstrated that these antibodies are capable of disrupting mitosis.189 CENP-A is a protein that is very similar to histone H3 of the H3/H4 nucleosomal core and is approximately 18 kD in size. It copurifies with H3/H4, but it has a centromere specific binding domain and is therefore distinct from H3 and H4.190,191 CENP-B is a DNA binding protein of 80kD and can be identified in 100% of all ACA-positive sera. It is distributed throughout the centromeric alpha-satellite heterochromatin below the kinetochore.192 CENP-C is a 140 kD protein that is a component of the kinetochore plate, which is essential for normal centromere function.193
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.
3D collagen porous scaffold carrying PLGA-PTX/SDF-1α recruits and promotes neural stem cell differentiation for spinal cord injury repair
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Zhixiang Li, Panpan Xu, Lijun Shang, Bingxu Ma, Huihui Zhang, Liangmin Fu, Yuanyuan Ou, Yingji Mao
The promotion of central neurogenesis requires certain biological signals more than anything else. Microtubule abnormalities have been reported in some nervous system degenerative diseases, such as Parkinson’s and Alzheimer’s. Hence, the use of microtubule stabilizers is a promising strategy for CNS generation. For SCI, axonal microtubule stability is crucial to ensure the growth of damaged axons. Paclitaxel, an anticancer drug, is often used in clinical tumor research because of its ability to interfere with cell division and affect the cell cycle. In the present study, the effects of different PTX concentrations on NSCs differentiation were investigated. Under normal physiological conditions, 10 ng/mL PLGA-PTX was more favorable for NSCs differentiation. The differentiation rate of neurons showed an initial trend of increase followed by a decrease, and higher doses of PTX had an inhibitory effect on neuronal differentiation. Recent studies have shown that low PTX doses not only exert a direct intrinsic effect on the neuronal differentiation of NSCs but also reverse the inhibitory effects of myelin proteins on neuronal axon growth [11]. In addition to microtubule stabilizers, some neurotrophins, including brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT3), play prominent roles in SCI repair [55, 56]. They are both able to enhance the neuronal differentiation of NSCs and provide another viable strategy.
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.