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991.
Luis O. Soto-Rojas Mar Pacheco-Herrero Paola A. Martínez-Gmez B. Berenice Campa-Crdoba Ricardo Aptiga-Prez Marcos M. Villegas-Rojas Charles R. Harrington Fidel de la Cruz Linda Garcs-Ramírez Jos Luna-Muoz 《International journal of molecular sciences》2021,22(4)
Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD. 相似文献
992.
A. D. Zhirnov S. A. Karimova L. V. Ovsyannikova O. A. Gubenko 《Metal Science and Heat Treatment》2003,45(1-2):23-25
Works aimed at solving the problem of replacing toxic cadmium coatings used for protection of aircraft steel parts are reviewed. Numerous electrolytic alloys based on zinc and zinc-bearing coatings of the Colsil and Dacromet types are suggested for the purpose. A VIAM-designed coating based on a Zn – Sn alloy in combination with a modified phosphate coating is considered. It is shown that the protective properties of the combined coating are close to those of a cadmium coating, and the former is recommended for commercial use. 相似文献
993.
Dr. Daisuke Okuno Dr. Noriho Sakamoto Dr. Mohammed S. O. Tagod Yoshiko Akiyama Dr. Sakiko Moriyama Dr. Takuto Miyamura Dr. Atsuko Hara Dr. Takashi Kido Dr. Hiroshi Ishimoto Prof. Yuji Ishimatsu Prof. Takashi Tanaka Prof. Jun Ishihara Prof. Kohsuke Takeda Prof. Yoshimasa Tanaka Prof. Hiroshi Mukae 《ChemMedChem》2021,16(16):2515-2523
Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis. 相似文献
994.
Luis O. Soto-Rojas B. Berenice Campa-Crdoba Charles R. Harrington Andrs Salas-Casas Mario Hernandes-Alejandro Ignacio Villanueva-Fierro Marely Bravo-Muoz Linda Garcs-Ramírez Fidel De La Cruz-Lpez Miguel ngel Ontiveros-Torres Goar Gevorkian Mar Pacheco-Herrero Jos Luna-Muoz 《International journal of molecular sciences》2021,22(7)
Alzheimer’s disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid β-peptide (Aβ) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aβ vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aβ deposits on the NVU and the blood–brain barrier (BBB) are unknown. In this study, we analyze different Aβ species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aβ and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aβ species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aβ in AD. 相似文献
995.
Sofía Valla Nourhan Hassan Daiana Lujn Vitale Daniela Madanes Fiorella Mercedes Spinelli Felipe C. O. B. Teixeira Burkhard Greve Nancy Adriana Espinoza-Snchez Carolina Cristina Laura Alaniz Martin Gtte 《International journal of molecular sciences》2021,22(11)
Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors. 相似文献
996.
Yurii S. Borovikov Daria D. Andreeva Stanislava V. Avrova Vladimir V. Sirenko Armen O. Simonyan Charles S. Redwood Olga E. Karpicheva 《International journal of molecular sciences》2021,22(12)
Point mutations in the genes encoding the skeletal muscle isoforms of tropomyosin can cause a range of muscle diseases. The amino acid substitution of Arg for Pro residue in the 90th position (R90P) in γ-tropomyosin (Tpm3.12) is associated with congenital fiber type disproportion and muscle weakness. The molecular mechanisms underlying muscle dysfunction in this disease remain unclear. Here, we observed that this mutation causes an abnormally high Ca2+-sensitivity of myofilaments in vitro and in muscle fibers. To determine the critical conformational changes that myosin, actin, and tropomyosin undergo during the ATPase cycle and the alterations in these changes caused by R90P replacement in Tpm3.12, we used polarized fluorimetry. It was shown that the R90P mutation inhibits the ability of tropomyosin to shift towards the outer domains of actin, which is accompanied by the almost complete depression of troponin’s ability to switch actin monomers off and to reduce the amount of the myosin heads weakly bound to F-actin at a low Ca2+. These changes in the behavior of tropomyosin and the troponin–tropomyosin complex, as well as in the balance of strongly and weakly bound myosin heads in the ATPase cycle may underlie the occurrence of both abnormally high Ca2+-sensitivity and muscle weakness. BDM, an inhibitor of myosin ATPase activity, and W7, a troponin C antagonist, restore the ability of tropomyosin for Ca2+-dependent movement and the ability of the troponin–tropomyosin complex to switch actin monomers off, demonstrating a weakening of the damaging effect of the R90P mutation on muscle contractility. 相似文献
997.
Rodriguez J. S. Duran J. F. Aguilar Y. Alcazar G. A. Perez Souza R. M. Zambrano O. A. 《Metallurgical and Materials Transactions A》2022,53(8):2961-2976
Metallurgical and Materials Transactions A - In the present work, the dynamic recrystallization and microstructural evolution of the family of advanced high-strength steels Fe18MnxAl0.74C are... 相似文献
998.
Grigoriev O.N. Panasyuk A.D. Brodnikovskyy M.P. Podchernyaeva I.O. Melakh L.M. Yurechko D.V. Vedel D.V. Kozak I.V. 《Powder Metallurgy and Metal Ceramics》2022,60(9-10):626-634
Powder Metallurgy and Metal Ceramics - Hot pressing was used to produce compact ceramic samples with the following composition (wt.%): 60 ZrB2 + 20 SiC + 20 (Al2O3 + 32 t-ZrO2). The tetragonal... 相似文献
999.
Rudenko A. V. Kataev A. A. Tkacheva O. Yu. Zaikov Yu. P. Pianykh A. A. Arkhipov G. V. 《Russian Journal of Non-Ferrous Metals》2022,63(1):1-6
Russian Journal of Non-Ferrous Metals - Viscosity of conventional cryolite-alumina melts NaF–AlF3–CaF2–Al2O3 with a cryolite ratio (xNaF/xAlF3, mol/mol) 2.3 was studied in... 相似文献
1000.
Turchanin M.A. Dreval L.O. Agraval P.G. Korsun V.A. Vodopyanova A.O. 《Powder Metallurgy and Metal Ceramics》2022,60(11-12):727-737
Powder Metallurgy and Metal Ceramics - The thermodynamic properties of liquid alloys in glass-forming systems were described in the framework of the associated solution model (ASM) according to the... 相似文献