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Endogenous Activation and Neurophysiological Functions of Acid-Sensing Ion Channels
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Wei-Zheng Zeng, Yi-Zhi Wang, Tian-Le Xu
The carbonic anhydrases (CAs) are a family of enzymes that reversibly catalyze CO2 hydration to H+ and HCO3− with catalytic rates of up to 106 s−1 (74). To date, at least 14 different isoforms are found in mammals, while their function is likely to differ depending on the site of expression. Some of these isozymes are cytosolic (CA1, CA2, CA3, CA7 and CA8); others are membrane-bound, where they can be targeted to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor (CA4) or a transmembrane segment (CA9, CA12 and CA14); CA5 is mitochondrial localized and CA6 is secreted in the saliva and milk (48,74). CAs have been shown to reversibly generate and buffer localized pH gradients in the CNS (75,76), CO2 sensing systems (77,78) and tumor cells (79). Small and rapidly diffusible buffers facilitate the displacement of proton equivalents in cells. As CO2 is an uncharged acid equivalent, it can diffuse without transiently binding to immobilized charged macromolecules. CAs also speed up the dissipation of localized pH gradients by accelerating the conversion of CO2 to H2CO3 (41).
Catalog of Herbs
Published in James A. Duke, Handbook of Medicinal Herbs, 2018
Per 100 g the fruit is reported to contain 47 to 52 calories, 85.3 to 87.0 g H2O, 0.4 to 0.7 g protein, 0.2 to 0.3 g fat, 11.6 to 13.7 g total carbohydrate, 0.4 to 0.5 g fiber, 0.3 to 0.4 g ash, 17 to 18 mg Ca, 8 to 12 mg P, 0.5 mg Fe, 1 to 2 mg Na, 125 to 146 mg K, 32 to 42 μg beta-carotene equivalent, 0.06 to 0.08 mg thiamine, 0.03 to 0.04 mg riboflavin, 0.2 to 0.3 mg niacin, and 17 to 61 (to 96) mg ascorbic acid.21 Cultivars may contain 1 to 5% citric acid (wild forms up to 8.6%), ca. 3.5% invert sugars, 7.5% saccharose, approaching 15% at maturity. Also reported are vanillin, methyl-n-propyl ketone, n-valerianic acid, isocapronic acid, acrylic acid, l( – )-malic acid, beta-methylthiopropionic acid methyl ester (and ethyl ester), 5-hydroxytryptamine, quinic acid-1,4-di-p-coumarin (my translation).33 The aromatics from the essential oils of the fruit include methanol, ethanol, n-propanol, isobutanol, n-pentanol, ethyl acetate, ethyl-n-butyrat, methylisovalerianate, methyl-n-capronate, methyl-n-caprylate, n-amyl-n-capronate, ethyl lactate, methyl-beta-methylthiolpropionate, ethyl-beta-methylthiolpropionate, and diacetyl, acetone, formaldehyde, acetaldehyde, furfurol, and 5-hydroxy-2-methylfurfurol.33 Steroid fractions of the lower leaves possess estrogenic activity.33
PLA scaffold
Published in Yoshinobu Onuma, Patrick W.J.C. Serruys, Bioresorbable Scaffolds, 2017
Kazuyuki Yahagi, Sho Torii, Erica Pacheco, Frank D. Kolodgie, Aloke V. Finn, Renu Virmani
Drug eluting bioresorbable scaffolds (BRSs) have emerged as a novel technology that is proposed to overcome these issues. One of the unique features of BRSs is the resorption of fully polymeric struts, with the expectation that the long-term absence of a rigid scaffold would restore the vessel to a natural state allowing for coronary vasomotion and avoiding future complications caused by permanent metal devices [4,5]. The Igaki-Tamai bioabsorbable scaffold (Kyoto Medical Planning Co. Ltd., Kyoto, Japan) was the first BRSs used in humans, which was made of poly-L-lactic acid (PLLA) without drug coating [4]. Nishio et al. reported the acceptable long-term safety with Igaki-Tmai scaffold in the first-in-man study which included 50 patients [6]. As expected, intravascular ultrasound (IVUS) studies showed that most of scaffolds disappeared within 3 years. Following on this novelty, many BRSs devices have been developed and have currently either completed clinical trials or are reaching the phase of clinical testing and two devices have received CE-Mark approval in Europe (ABSORB BVSs, Abbott Vascular, CA) [7] and the DESolve stent (Elixir Medical, CA) [8,9] while the former has already reported the FDA-initiated large, multicenter, randomized clinical trial against XIENCE (Abbott Vascular, CA) DESs, showing noninferiority with respect to target lesion failure at 1 year [10].
Proteomic profiling of carbonic anhydrase CA3 in skeletal muscle
Published in Expert Review of Proteomics, 2021
Paul Dowling, Stephen Gargan, Margit Zweyer, Hemmen Sabir, Dieter Swandulla, Kay Ohlendieck
The various groupings of α-CAs consist of the cytosolic isoforms CA1, CA2, CA3, CA7, and CA13, the CA-related proteins (CARPs) CA8, CA10, and CA11 of the cytosol, the membrane-associated isoforms CA4, CA9, CA12, CA14, and CA15, the mitochondrial isoforms CA5a and CA5b, and the secreted isoform CA6 [5,10,12]. The tissue distribution of CAs is summarized in Figure 2 and the comparative mass spectrometric identification of these proteins in mouse diaphragm, gastrocnemius muscle, extraocular muscle, heart, brain, liver, kidney, spleen, the stomach/pancreas interface, saliva, serum, and urine are listed in Table 2. Data are based on recent proteomic surveys of mouse tissues and biofluids [42–49] using optimized mass spectrometric approaches as described in detail by Dowling et al. [50].
Nitroimidazole-based inhibitors DTP338 and DTP348 are safe for zebrafish embryos and efficiently inhibit the activity of human CA IX in Xenopus oocytes
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Ashok Aspatwar, Holger M. Becker, Nanda Kumar Parvathaneni, Milka Hammaren, Aleksandra Svorjova, Harlan Barker, Claudiu T. Supuran, Ludwig Dubois, Philippe Lambin, Mataleena Parikka, Seppo Parkkila, Jean-Yves Winum
Interestingly, embryos exposed to either of the inhibitors at a concentration of 100 µM or above generally showed mild to significant ataxic swim pattern (abnormal movement), which is likely caused by neurotoxicity, at the end of five days exposure. This is similar to the swim pattern of fish which have the CA8 gene knocked down, a gene associated with motor coordination function in human, mice and zebrafish43. Apart from ataxic swim pattern none of the fish showed significant defects in morphologic phenotype. However, further studies using molecular and electron microscopic techniques could reveal the precise changes in the brain. Based on the results of the present study, it is important to consider the dose of the inhibitors critical either for sensitizing the tumours or for the treatment of the solid tumours.
N-thioalkylcarbazoles derivatives as new anti-proliferative agents: synthesis, characterisation and molecular mechanism evaluation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Maria Stefania Sinicropi, Domenico Iacopetta, Camillo Rosano, Rosario Randino, Anna Caruso, Carmela Saturnino, Noemi Muià, Jessica Ceramella, Francesco Puoci, Manuela Rodriquez, Pasquale Longo, Maria Rosaria Plutino
Apoptosis was detected by the TUNEL assay, according to the guidelines of the manufacturer (CF™488A TUNEL Assay Apoptosis Detection Kit, Biotium, Hayward, CA)8. Briefly, cells were grown on glass coverslips and, after treatment, they were washed trice with PBS, then methanol-fixed at −20 °C for 15 min. Fixed cells were washed trice with 0.01% (V/V) Triton X-100 in PBS and incubated with 100 µL of TUNEL equilibration buffer for 5 min. After its removal, 50 µL of TUNEL reaction mixture containing 1 µL of terminal deoxynucleotidyl transferase (TdT) were added to each sample and incubated in a dark and humidified chamber for 2 h at 37 °C. Samples were washed trice with ice-cold phosphate-buffered saline (PBS) containing 0.1% Triton X-100 and 5 mg/mL bovine serum albumin (BSA). 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) (0.2 µg/mL) counterstain was performed (10 min, 37 °C, dark and humidified conditions). After three additional washes with cold PBS, one drop of mounting solution was added, then they were observed and imaged under a fluorescence microscope (Leica DM 6000, Leica, Frankfurt am Main, Germany) (20× magnification) with excitation/emission wavelength maxima of 490 nm/515 nm (CFTM488A) or 350 nm/460 nm (DAPI). Representative fields were shown. The experiments were repeated three times41.